title: Lixisenatide Therapy in Older Patients With Type 2 Diabetes Inadequately Controlled on Their Current Antidiabetic Treatment: The GetGoal-O Randomized Trial Efficacy and safety of thrice-weekly insulin degludec in elderly patients with type 2 diabetes assessed by continuous glucose monitoring. Effects of Once‐Weekly Exenatide on Cardiovascular Outcomes in Type 2 Diabetes Mobile App-Based Interventions to Support Diabetes Self-Management: A Systematic Review of Randomized Controlled Trials to Identify Functions Associated with Glycemic Efficacy Canagliflozin and Heart Failure in Type 2 Diabetes Mellitus Canagliflozin and cardiovascular and renal events in type 2 diabetes Insulin provision therapy and mortality in older adults with diabetes mellitus and stable ischemic heart disease: Insights from BARI-2D trial. Diabetes and Cognitive Decline in Older Adults: The Ginkgo Evaluation of Memory Study Smart Care Based on Telemonitoring and Telemedicine for Type 2 Diabetes Care: Multi-Center Randomized Controlled Trial. Diabetes in Older Adults Assessing the Safety of Sitagliptin in Older Participants in the Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS) Impact of empagliflozin added on to basal insulin in type 2 diabetes inadequately controlled on basal insulin: a 78‐week randomized, double‐blind, placebo‐controlled trial Efficacy and Safety of Saxagliptin in Older Participants in the SAVOR-TIMI 53 Trial A Dietary Supplement Containing Cinnamon, Chromium and Carnosine Decreases Fasting Plasma Glucose and Increases Lean Mass in Overweight or Obese Pre-Diabetic Subjects: A Randomized, Placebo-Controlled Trial Efficacy and Safety of Canagliflozin in Individuals Aged 75 and Older with Type 2 Diabetes Mellitus: A Pooled Analysis Cardiovascular Events and Geriatric Scale Scores in Elderly (70 Years Old and Above) Type 2 Diabetic Patients at Inclusion in the GERODIAB Cohort An evaluation of the effectiveness of a multi-modal intervention in frail and pre-frail older people with type 2 diabetes - the MID-Frail study: study protocol for a randomised controlled trial Chronic Low-Calorie Sweetener Use and Risk of Abdominal Obesity among Older Adults: A Cohort Study Durability of glycemic control with insulin lispro mix 75/25 versus insulin glargine for older patients with type 2 diabetes Effects of empagliflozin on blood pressure and markers of arterial stiffness and vascular resistance in patients with type 2 diabetes Linagliptin for patients aged 70 years or older with type 2 diabetes inadequately controlled with common antidiabetes treatments: a randomised, double-blind, placebo-controlled trial Safety of Sitagliptin in Elderly Patients with Type 2 Diabetes: A Pooled Analysis of 25 Clinical Studies Diabetes Risk Factors, Diabetes Risk Algorithms, and the Prediction of Future Frailty: The Whitehall II Prospective Cohort Study The “Sarcopenia and Physical fRailty IN older people: multi-componenT Treatment strategies” (SPRINTT) randomized controlled trial: design and methods GERODIAB: Glycaemic control and 5-year morbidity/mortality of type 2 diabetic patients aged 70 years and older: 1. Description of the population at inclusion. New insulin glargine 300 U/ml compared with glargine 100 U/ml in insulin-naïve people with type 2 diabetes on oral glucose-lowering drugs: a randomized controlled trial (EDITION 3) Structural Alteration of Gut Microbiota during the Amelioration of Human Type 2 Diabetes with Hyperlipidemia by Metformin and a Traditional Chinese Herbal Formula: a Multicenter, Randomized, Open Label Clinical Trial Once-weekly dulaglutide versus bedtime insulin glargine, both in combination with prandial insulin lispro, in patients with type 2 diabetes (AWARD-4): a randomised, open-label, phase 3, non-inferiority study The design and rationale for the Dapagliflozin Effect on Cardiovascular Events (DECLARE)–TIMI 58 Trial Efficacy and safety of dapagliflozin monotherapy in people with Type 2 diabetes: a randomized double-blind placebo-controlled 102-week trial. Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes. Lixisenatide in Patients with Type 2 Diabetes and Acute Coronary Syndrome. Canagliflozin and Cardiovascular and Renal Events in Type 2 Diabetes Aerobic or Resistance Exercise, or Both, in Dieting Obese Older Adults Diabetes and risk of frailty and its potential mechanisms: a prospective cohort study of older adults. New Insulin Glargine 300 Units/mL Versus Glargine 100 Units/mL in People With Type 2 Diabetes Using Oral Agents and Basal Insulin: Glucose Control and Hypoglycemia in a 6-Month Randomized Controlled Trial (EDITION 2) Canagliflozin for Primary and Secondary Prevention of Cardiovascular Events
abstract: OBJECTIVE To evaluate the efficacy and safety of lixisenatide versus placebo on glycemic control in older patients with type 2 diabetes uncontrolled on their current antidiabetic treatment . RESEARCH DESIGN AND METHODS In this phase III , double-blind , r and omized , placebo-controlled , two-arm , parallel-group , multicenter trial , patients aged ≥70 years were r and omized to receive once-daily lixisenatide 20 μg or placebo before breakfast concomitantly with their existing antidiabetic therapy ( including insulin ) for 24 weeks . Patients at risk for malnutrition or with moderate to severe cognitive impairment were excluded . The primary end point was absolute change in HbA1c from baseline to week 24 . Secondary end points included change from baseline to week 24 in 2-h postpr and ial plasma glucose ( PPG ) and body weight . RESULTS A total of 350 patients were r and omized . HbA1c decreased substantially with lixisenatide ( −0.57 % [ 6.2 mmol/mol ] ) compared with placebo ( + 0.06 % [ 0.7 mmol/mol ] ) from baseline to week 24 ( P < 0.0001 ) . Mean reduction in 2-h PPG was significantly greater with lixisenatide ( −5.12 mmol/L ) than with placebo ( −0.07 mmol/L ; P < 0.0001 ) . A greater decrease in body weight was observed with lixisenatide ( −1.47 kg ) versus placebo ( −0.16 kg ; P < 0.0001 ) . The safety profile of lixisenatide in this older population , including rates of nausea and vomiting , was consistent with that observed in other lixisenatide studies . Hypoglycemia was reported in 17.6 % of patients with lixisenatide versus 10.3 % with placebo . CONCLUSIONS In nonfrail older patients uncontrolled on their current antidiabetic treatment , lixisenatide was superior to placebo in HbA1c reduction and in targeting postpr and ial hyperglycemia , with no unexpected safety findings As life expectancy becomes longer in Japan , there has been an increase of elderly patients with type 2 diabetes who need insulin therapy but can not perform self-injection due to dementia or other conditions . Therefore , the aim of this study was to investigate the efficacy and safety of thrice-weekly insulin degludec therapy in elderly patients with poorly controlled diabetes . The subjects were 22 hospitalized elderly Japanese patients with type 2 diabetes who had difficulty with self-injection . After becoming stable on once-daily insulin degludec treatment , they were assigned to continue once-daily injection ( OD group ) or were switched to thrice-weekly injection ( TW group ) for one week . In the TW group , insulin degludec ( IDeg ) was injected at twice the OD dose before lunch on Monday , Wednesday , and Friday . Glycemic control was assessed by continuous glucose monitoring ( CGM ) over 7 days . The mean 7-day glucose level ( 131±25 mg/dL with OD vs. 152±30 mg/dL with TW , p=0.11 ) and the mean 7-day st and ard deviation ( 32±10 mg/dL with OD vs. 36±14 mg/dL with TW , p=0.45 ) did not differ significantly between the two groups . The percent duration of glucose < 70 mg/dL ( 2.4±3.1 % with OD vs. 1.3±2.5 % with TW , p=0.39 ) and glucose > 200 mg/dL ( 7.2±12.1 % with OD vs. 15.6±18.0 % with TW , p=0.22 ) over 7 days also showed no significant differences between the two groups . In conclusion , thrice-weekly IDeg provided by a visiting nurse could be a practical option for elderly diabetic patients who have difficulty performing self-injection of insulin BACKGROUND The cardiovascular effects of adding once‐weekly treatment with exenatide to usual care in patients with type 2 diabetes are unknown . METHODS We r and omly assigned patients with type 2 diabetes , with or without previous cardiovascular disease , to receive subcutaneous injections of extended‐release exenatide at a dose of 2 mg or matching placebo once weekly . The primary composite outcome was the first occurrence of death from cardiovascular causes , nonfatal myocardial infa rct ion , or nonfatal stroke . The co primary hypotheses were that exenatide , administered once weekly , would be noninferior to placebo with respect to safety and superior to placebo with respect to efficacy . RESULTS In all , 14,752 patients ( of whom 10,782 [ 73.1 % ] had previous cardiovascular disease ) were followed for a median of 3.2 years ( interquartile range , 2.2 to 4.4 ) . A primary composite outcome event occurred in 839 of 7356 patients ( 11.4 % ; 3.7 events per 100 person‐years ) in the exenatide group and in 905 of 7396 patients ( 12.2 % ; 4.0 events per 100 person‐years ) in the placebo group ( hazard ratio , 0.91 ; 95 % confidence interval [ CI ] , 0.83 to 1.00 ) , with the intention‐to‐treat analysis indicating that exenatide , administered once weekly , was noninferior to placebo with respect to safety ( P<0.001 for noninferiority ) but was not superior to placebo with respect to efficacy ( P=0.06 for superiority ) . The rates of death from cardiovascular causes , fatal or nonfatal myocardial infa rct ion , fatal or nonfatal stroke , hospitalization for heart failure , and hospitalization for acute coronary syndrome , and the incidence of acute pancreatitis , pancreatic cancer , medullary thyroid carcinoma , and serious adverse events did not differ significantly between the two groups . CONCLUSIONS Among patients with type 2 diabetes with or without previous cardiovascular disease , the incidence of major adverse cardiovascular events did not differ significantly between patients who received exenatide and those who received placebo . ( Funded by Amylin Pharmaceuticals ; EXSCEL Clinical Trials.gov number , NCT01144338 . Background Mobile health apps for diabetes self-management have different functions . However , the efficacy and safety of each function are not well studied , and no classification is available for these functions . Objective The aims of this study were to ( 1 ) develop and vali date a taxonomy of apps for diabetes self-management , ( 2 ) investigate the glycemic efficacy of  mobile app-based interventions among adults with diabetes in a systematic review of r and omized controlled trials ( RCTs ) , and ( 3 ) explore the contribution of different function to the effectiveness of entire app-based interventions using the taxonomy . Methods We developed a 3-axis taxonomy with columns of clinical modules , rows of functional modules and cells of functions with risk assessment s. This taxonomy was vali date d by review ing and classifying commercially available diabetes apps . We search ed MEDLINE , EMBASE , the Cochrane Central Register of Controlled Trials , the Chinese Biomedical Literature Data base , and Clinical Trials.gov from January 2007 to May 2016 . We included RCTs of adult out patients with diabetes that compared using  mobile app-based interventions with usual care alone . The mean differences ( MDs ) in hemoglobin A1c ( HbA1c ) concentrations and risk ratios of adverse events were pooled using a r and om-effects meta- analysis . After taxonomic classification , we performed exploratory subgroup analyses of the presence or absence of each module across the included app-based interventions . Results Across 12 included trials involving 974 participants , using app-based interventions was associated with a clinical ly significant reduction of HbA1c ( MD 0.48 % , 95 % CI 0.19%-0.78 % ) without excess adverse events . Larger HbA1c reductions were noted among patients with type 2 diabetes than those with type 1 diabetes ( MD 0.67 % , 95 % CI 0.30%-1.03 % vs MD 0.37 % , 95 % CI –0.12%-0.86 % ) . Having a complication prevention module in app-based interventions was associated with a greater HbA1c reduction ( with complication prevention : MD 1.31 % , 95 % CI 0.66%-1.96 % vs without : MD 0.38 % , 95 % CI 0.09%-0.67 % ; intersubgroup P=.01 ) , as was having a structured display ( with structured display : MD 0.69 % , 95 % CI 0.32%-1.06 % vs without : MD 0.69 % , 95 % CI –0.18%-0.53 % ; intersubgroup P=.03 ) . However , having a clinical decision-making function was not associated with a larger HbA1c reduction ( with clinical decision making : MD 0.19 % , 95 % CI –0.24%-0.63 % vs without : MD 0.61 % , 95 % CI 0.27%-0.95 % ; intersubgroup P=.14 ) . Conclusions The use of mobile app-based interventions yields a clinical ly significant HbA1c reduction among adult out patients with diabetes , especially among those with type 2 diabetes . Our study suggests that the clinical decision-making function needs further improvement and evaluation before being added to apps Background : Canagliflozin is a sodium glucose cotransporter 2 inhibitor that reduces the risk of cardiovascular events . We report the effects on heart failure ( HF ) and cardiovascular death overall , in those with and without a baseline history of HF , and in other participant subgroups . Methods : The CANVAS Program ( Canagliflozin Cardiovascular Assessment Study ) enrolled 10 142 participants with type 2 diabetes mellitus and high cardiovascular risk . Participants were r and omly assigned to canagliflozin or placebo and followed for a mean of 188 weeks . The primary end point for these analyses was adjudicated cardiovascular death or hospitalized HF . Results : Participants with a history of HF at baseline ( 14.4 % ) were more frequently women , white , and hypertensive and had a history of prior cardiovascular disease  ( all P<0.001 ) . Greater proportions of these patients were using therapies such as blockers of the renin angiotensin aldosterone system , diuretics , and & bgr;-blockers at baseline ( all P<0.001 ) . Overall , cardiovascular death or hospitalized HF was reduced in those treated with canagliflozin compared with placebo ( 16.3 versus 20.8 per 1000 patient-years ; hazard ratio [ HR ] , 0.78 ; 95 % confidence interval [ CI ] , 0.67–0.91 ) , as was fatal or hospitalized HF ( HR , 0.70 ; 95 % CI , 0.55–0.89 ) and hospitalized HF alone ( HR , 0.67 ; 95 % CI , 0.52–0.87 ) . The benefit on cardiovascular death or hospitalized HF may be greater in patients with a prior history of HF ( HR , 0.61 ; 95 % CI , 0.46–0.80 ) compared with those without HF at baseline ( HR , 0.87 ; 95 % CI , 0.72–1.06 ; P interaction = 0.021 ) . The effects of canagliflozin compared with placebo on other cardiovascular outcomes and key safety outcomes were similar in participants with and without HF at baseline ( all interaction P values > 0.130 ) , except for a possibly reduced absolute rate of events attributable to osmotic diuresis among those with a prior history of HF ( P=0.03 ) . Conclusions : In patients with type 2 diabetes mellitus and an elevated risk of cardiovascular disease , canagliflozin reduced the risk of cardiovascular death or hospitalized HF across a broad range of different patient subgroups . Benefits may be greater in those with a history of HF at baseline . Clinical Trial Registration : URL : https://www . clinical trials.gov . Unique identifiers : NCT01032629 and NCT01989754 ABSTRACT Review of : Neal B , Perkovic V , Mahaffey K , et al. Canagliflozin and cardiovascular and renal events in type 2 diabetes . N Engl J Med . 2017;377:644–657 . The report combines the data from two trials , CANVAS and CANVAS-Renal , which were design ed to evaluate the safety and effect of canagliflozin , an SGLT-2 inhibitor , on the appearance of cardiovascular and renal events in patients with type 2 diabetes . Enrollees were patients with type 2 diabetes of at least 30 years of age , with a glycated hemoglobin of > or equal to 7.0 % and < or equal to 10.5 % . Patients either had to have preexisting cardiovascular disease or to be at elevated risk for cardiovascular disease , and to have an estimated glomerular filtration rate ( eGFR ) of > 30 ml/min . Patients were r and omized to canagliflozin at doses of either 100 mg or 300 mg or matching placebo in CANVAS , and to canagliflozin 100 mg with a possible increase to 300 mg , or placebo , in CANVAS-Renal . Physicians were instructed to continue appropriate diabetic management and other therapies in accordance with the best practice s in their community . There was a significant 14 % reduction in the combined endpoint of cardiovascular events of death from cardiovascular causes , nonfatal myocardial infa rct ion , or nonfatal stroke in the canagliflozin treated patients . There was also a pattern of improvement in markers of renal disease , including the change in the level and nature of albuminuria , a 40 % decrease in the glomerular filtration rate , the need for renal replacement therapy , or death from renal causes . This study exp and s the scope of SGLT-2 inhibitor therapy to prevent cardiovascular disease in diabetic patients beyond those with preexisting cardiovascular disease studied in the previous empagliflozin study , raising the question as to whether SGLT-2 inhibitor therapy should be considered appropriate for most , if not all , type 2 diabetes patients , not only to control hyperglycemia but also to reduce cardiovascular and renal events IMPORTANCE Optimal strategies for glucose control in very old adults with diabetes and stable ischemic heart disease ( SIHD ) are unclear . OBJECTIVE To compare the effects of insulin provision ( IP ) therapy versus insulin sensitizing ( IS ) therapy for glycemic control in older ( ≥75years ) and younger ( < 75years ) adults with type II diabetes ( DM ) and SIHD . DESIGN , SETTING , AND PARTICIPANTS Adults enrolled in the Bypass Angioplasty Revascularization Investigation 2 Diabetes ( BARI 2D ) were studied . The BARI 2D study population ( all with type II DM and SIHD ) was r and omized twice : ( 1 ) between revascularization plus intensive medical therapy versus intensive medical therapy alone , and ( 2 ) between IP versus IS therapies . The primary endpoint was all-cause-mortality over five-year follow-up . In this sub study outcomes related to IP vs. IS are assessed in relation to age . Adults aged ≥75years who received IP versus IS are compared to those < 75years who received  IP  versus IS . Multivariate Cox regression analysis was used to evaluate the effects of IP vs. IS on outcomes in the two age groups . RESULTS 2368 subjects with SIHD and DM were enrolled in BARI 2D ; 182 ( 8 % ) were ≥75years . Compared to younger subjects , the older cohort had lower BMI , higher diuretic use , worse kidney function , and increased history of heart failure . Within the older cohort , the IP and IS subgroups were similar in respect to baseline cardiovascular risk factors , medications , and coronary artery disease severity . During follow-up , the older subjects receiving IP therapy had higher cardiovascular mortality compared to those receiving IS therapy ( 16 % vs. 11 % , p=0.040 ) . Using Cox proportional hazards analysis , the older IP subjects were at increased risk for all-cause-mortality ( hazard ratio 1.89 , CI 1.1 - 3.2 , p=0.020 ) . No mortality difference  between IP and IS was observed in those < 75years of age . CONCLUSION AND RELEVANCE Among adults with diabetes and SIHD aged ≥75years  , IP therapy may be associated with increased mortality  compared to IS therapy . Additional studies are needed to further refine optimal treatment strategies for diabetes and SIHD in old age Background Previous studies have shown that individuals with diabetes exhibit accelerated cognitive decline . However , method ological limitations have limited the quality of this evidence . Heterogeneity in study design , cognitive test administration , and methods of analysis of cognitive data have made it difficult to synthesize and translate findings to practice . We analyzed longitudinal data from the Ginkgo Evaluation of Memory Study to test our hypothesis that older adults with diabetes have greater test-specific and domain-specific cognitive declines compared to older adults without diabetes . Methods Tests of memory , visuo-spatial construction , language , psychomotor speed , and executive function  were administered . Test scores were st and ardized to z-scores and averaged to yield domain scores . Linear r and om effects models were used to compare baseline differences and changes over time in test and domain scores among individuals with and without diabetes . Results Among the 3,069 adults , aged 72 - 96 years , 9.3 % reported diabetes . Over a median follow-up of 6.1 years , participants with diabetes exhibited greater baseline differences in a test of executive function ( trail making test , Part B ) and greater declines in a test of language ( phonemic verbal fluency ) . For the composite cognitive domain scores , participants with diabetes exhibited lower baseline executive function and global cognition domain scores , but no significant differences in the rate of decline . Conclusions Identifying cognitive domains most affected by diabetes can lead to targeted risk modification , possibly in the form of lifestyle interventions such as diet and physical activity , which we know to be beneficial for improving vascular risk factors , such as diabetes , and therefore may reduce the risk of executive dysfunction and possible dementia BACKGROUND This study was performed to determine the effectiveness of the Smart Care service on glucose control based on telemedicine and telemonitoring compared with conventional treatment in patients with type 2 diabetes . MATERIAL S AND METHODS This 24-week prospect i ve multi-center r and omized controlled trial involved 338 adult patients with type 2 diabetes at four university hospitals in South Korea . The patients were r and omly assigned to a control group ( group A , n = 113 ) , a telemonitoring group ( group B , n = 113 ) , or a telemedicine group ( group C , n = 112 ) . Patients in the telemonitoring group visited the outpatient clinic regularly , accompanied by an additional telemonitoring service that included remote glucose monitoring with automated patient decision support by text . Remote glucose monitoring was identical in the telemedicine group , but assessment by outpatient visits was replaced by video conferencing with an endocrinologist . RESULTS The adjusted net reductions in HbA1c concentration after 24 weeks were similar in the conventional , telemonitoring , and telemedicine groups ( -0.66 % ± 1.03 % vs. -0.66 % ± 1.09 % vs. -0.81 % ± 1.05 % ; p > 0.05 for each pairwise comparison ) . Fasting glucose concentrations were lower in the telemonitoring and telemedicine groups than in the conventional group . Rates of hypoglycemia were lower in the telemedicine group than in the other two groups , and compliance with medication was better in the telemonitoring and telemedicine than in the conventional group . No serious adverse events were associated with telemedicine . CONCLUSIONS Telehealthcare was as effective as conventional care at improving glycemia in patients with type 2 diabetes without serious adverse effects More than 25 % of the U.S. population aged ≥65 years has diabetes ( 1 ) , and the aging of the overall population is a significant driver of the diabetes epidemic . Although the burden of diabetes is often described in terms of its impact on working-age adults , diabetes in older adults is linked to higher mortality , reduced functional status , and increased risk of institutionalization ( 2 ) . Older adults with diabetes are at substantial risk for both acute and chronic microvascular and cardiovascular complications of the disease . Despite having the highest prevalence of diabetes of any age-group , older persons and /or those with multiple comorbidities have often been excluded from r and omized controlled trials of treatments— and treatment targets — for diabetes and its associated conditions . Heterogeneity of health status of older adults ( even within an age range ) and the dearth of evidence from clinical trials present challenges to determining st and ard intervention strategies that fit all older adults . To address these issues , the American Diabetes Association ( ADA ) convened a Consensus Development Conference on Diabetes and Older Adults ( defined as those aged ≥65 years ) in February 2012 . Following a series of scientific presentations by experts in the field , the writing group independently developed this consensus report to address the following questions : 1 . What is the epidemiology and pathogenesis of diabetes in older adults ? 2 . What is the evidence for preventing and treating diabetes and its common comorbidities in older adults ? 3 . What current guidelines exist for treating diabetes in older adults ? 4 . What issues need to be considered in individualizing treatment recommendations for older adults ? 5 . What are consensus recommendations for treating older adults with or at risk for diabetes ? 6 . How can gaps in the evidence best be filled ? According to the most recent surveillance data , the prevalence of diabetes among U.S. adults aged ≥65 years varies from 22 to 33 % , depending on the diagnostic criteria OBJECTIVE Limited data exist regarding safety and efficacy of antihyperglycemic drugs in older patients with type 2 diabetes . The Trial Evaluating Cardiovascular Outcomes with Sitagliptin ( TECOS ) was a r and omized , double-blind , placebo-controlled trial assessing the impact of sitagliptin on a primary composite outcome of cardiovascular death , nonfatal stroke , nonfatal myocardial infa rct ion , or unstable angina hospitalizations in patients with type 2 diabetes ( HbA1c ≥6.5 % [ 48 mmol/mol ] and ≤8.0 % [ 64 mmol/mol ] ) and cardiovascular disease . We analyzed baseline characteristics and clinical outcomes for TECOS participants aged ≥75 years . RESEARCH DESIGN AND METHODS Clinical and safety event summaries are presented for older versus younger participants and for the treatment groups within the older cohort . RESULTS Of 14,351 participants with age recorded , 2,004 ( 14 % ) were ≥75 years old ( mean age 78.3 years [ SD 3.1 ] ) , with 68 % men and type 2 diabetes duration median 12.0 years ( IQR 7 , 21 ) . During 2.9 years median follow-up , older participants had higher rates of the primary outcome ( 6.46 vs. 3.67 events per 100 person-years ; hazard ratio 1.72 [ 95 % CI 1.52–1.94 ] ) , death ( 2.52 [ 2.20–2.89 ] ) , severe hypoglycemia ( 1.53 [ 1.15–2.03 ] ) , and fractures ( 1.84 [ 1.44–2.35 ] ) . In the older cohort , sitagliptin did not significantly impact the primary composite ( 1.10 [ 0.89–1.36 ] ) , death ( 1.05 [ 0.83–1.32 ] ) , heart failure hospitalization ( 0.99 [ 0.65–1.49 ] ) , severe hypoglycemia ( 1.03 [ 0.62–1.71 ] ) , rates of acute pancreatitis and pancreatic cancer , or serious adverse events . CONCLUSIONS Among older patients with well-controlled type 2 diabetes and cardiovascular disease , sitagliptin had neutral effects on cardiovascular risk and raised no significant safety concerns Aims To investigate the efficacy and tolerability of empagliflozin added to basal insulin‐treated type 2 diabetes . Methods Patients inadequately controlled [ glycated haemoglobin ( HbA1c ) > 7 to ≤10 % ( > 53 to ≤86 mmol/mol ) ] on basal insulin ( glargine , detemir , NPH ) were r and omized to empagliflozin 10 mg ( n = 169 ) , empagliflozin 25 mg ( n = 155 ) or placebo ( n = 170 ) for 78 weeks . The baseline characteristics were balanced among the groups [ mean HbA1c 8.2 % ( 67 mmol/mol ) , BMI 32.2 kg/m2 ] . The basal insulin dose was to remain constant for 18 weeks , then could be adjusted at investigator 's discretion . The primary endpoint was change from baseline in HbA1c at week 18 . Key secondary endpoints were changes from baseline in HbA1c and insulin dose at week 78 . Results At week 18 , the adjusted mean ± st and ard error changes from baseline in HbA1c were 0.0 ± 0.1 % ( −0.1 ± 0.8 mmol/mol ) for placebo , compared with −0.6 ± 0.1 % ( −6.2 ± 0.8 mmol/mol ) and −0.7 ± 0.1 % ( −7.8 ± 0.8 mmol/mol ) for empagliflozin 10 and 25 mg , respectively ( both p < 0.001 ) . At week 78 , empagliflozin 10 and 25 mg significantly reduced HbA1c , insulin dose and weight vs placebo ( all  p < 0.01 ) , and empagliflozin 10 mg significantly reduced systolic blood pressure vs placebo ( p = 0.004 ) . Similar percentages of patients had confirmed hypoglycaemia in all groups ( 35–36 % ) . Events consistent with urinary tract infection were reported in 9 , 15 and 12 % of patients on  placebo , empagliflozin 10 and 25 mg , and events consistent with genital infection were reported in 2 , 8 and 5 % , respectively .  Conclusions Empagliflozin for 78 weeks added to basal insulin improved glycaemic control and reduced weight with a similar risk of hypoglycaemia to placebo OBJECTIVE To examine the safety and cardiovascular ( CV ) effects of saxagliptin in the predefined elderly ( ≥65 years ) and very elderly ( ≥75 years ) sub population s of the Saxagliptin Assessment of Vascular Outcomes Recorded in Patients with Diabetes Mellitus – Thrombolysis in Myocardial Infa rct ion 53 ( SAVOR-TIMI 53 ) trial . RESEARCH DESIGN AND METHODS Individuals ≥40 years ( n = 16,492 ; elderly , n = 8,561 ; very elderly , n = 2,330 ) with HbA1c ≥6.5 % ( 47.5 mmol/mol ) and ≤12.0 % ( 107.7 mmol/mol ) were r and omized ( 1:1 ) to saxagliptin  ( 5 or 2.5 mg daily ) or placebo in a double-blind trial for a median follow-up of 2.1 years . RESULTS The hazard ratio ( HR ) for the comparison of saxagliptin versus placebo for the primary end point ( composite of CV mortality , myocardial infa rct ion , or ischemic stroke ) was 0.92 for elderly patients vs. 1.15 for patients < 65 years ( P = 0.06 ) and 0.95 for very elderly patients . The HRs for the secondary composite end points in the entire cohort , elderly cohort , and very elderly cohort were similar . Although saxagliptin increased the risk of hospitalization for heart failure in the overall saxagliptin population , there was no age-based treatment interaction ( P = 0.76 for elderly patients vs. those < 65 years ; P = 0.34 for very elderly patients vs. those < 75 years ) . Among saxagliptin-treated individuals with baseline HbA1c ≥7.6 % ( 59.6 mmol/mol ) , the mean change from baseline HbA1c at 2 years was −0.69 % , −0.64 % , −0.66 % , and −0.66 % for those ≥65 , < 65 , ≥75 , and < 75 years old , respectively . The incidence of overall adverse events ( AEs ) and serious AEs was similar between saxagliptin and placebo in all cohorts ; however , hypoglycemic events were higher for saxagliptin versus placebo regardless of age . CONCLUSIONS The SAVOR-TIMI 53 trial supports the overall CV safety of saxagliptin in a robust number of elderly and very elderly participants , although the risk of heart failure hospitalization was increased irrespective of age category . AEs and serious AEs as well as glycemic efficacy of saxagliptin in elderly patients are similar to those found in younger patients Background Preventing or slowing the progression of prediabetes to diabetes is a major therapeutic issue . Objectives Our aim was to evaluate the effects of 4-month treatment with a dietary supplement containing cinnamon , chromium and carnosine in moderately obese or overweight pre-diabetic subjects , the primary outcome being change in fasting plasma glucose ( FPG ) level . Other parameters of plasma glucose homeostasis , lipid profile , adiposity and inflammatory markers were also assessed . Methods In a r and omized , double-blind , placebo-controlled study , 62 subjects with a FPG level ranging from 5.55 to 7 mmol/L and a body mass index ≥25 kg/m2 , unwilling to change their dietary and physical activity habits , were allocated to receive a 4-month treatment with either 1.2 g/day of the dietary supplement or placebo . Patients were followed up until 6 months post-r and omization . Results Four-month treatment with the dietary supplement  decreased FPG compared to placebo ( -0.24±0.50 vs + 0.12±0.59 mmol/L , respectively , p = 0.02 ) , without detectable significant changes in HbA1c . Insulin sensitivity markers , plasma insulin , plasma lipids and inflammatory markers did not differ between the treatment groups . Although there were no significant differences in changes in body weight and energy or macronutrient intakes between the two groups , fat-free mass ( % ) increased with the dietary supplement compared to placebo ( p = 0.02 ) . Subjects with a higher FPG level and a milder inflammatory state at baseline benefited most from the dietary supplement . Conclusions Four-month treatment with a dietary supplement containing cinnamon , chromium and carnosine decreased FPG and increased fat-free mass in overweight or obese pre-diabetic subjects . These beneficial effects might open up new avenues in the prevention of diabetes . Trial Registration Clinical Trials.gov Objectives To compare the efficacy and safety of canagliflozin , a sodium glucose co‐transporter 2 inhibitor developed to treat type 2 diabetes mellitus ( T2DM ) , in individuals younger than 75 and those aged 75 and older . Design R and omized Phase 3 studies . Setting International study centers . Participants Adults with T2DM . Measurements Changes from baseline in glycosylated hemoglobin ( HbA1c ) , fasting plasma glucose ( FPG ) , blood pressure ( BP ) , and body weight were measured . Efficacy was evaluated using pooled data from six r and omized , double‐blind , placebo‐controlled studies ( N = 4,158 ; n = 3,975 aged < 75 , n = 183 aged ≥75 ) . Safety was assessed based on adverse event ( AE ) reports from eight r and omized , double‐blind , placebo‐ and active‐controlled studies ( N = 9,439 ; n = 8,949 aged < 75 , n = 490 aged ≥75 ) . Results Canagliflozin 100 and 300 mg were associated with placebo‐subtracted mean reductions in HbA1c in participants younger than 75 ( −0.69 % and −0.85 % , respectively ) and aged 75 and older ( −0.65 % and −0.55 % , respectively ) . Dose‐related reductions in FPG , body weight , and BP were seen with canagliflozin 100 and 300 mg in participants in both age groups . Overall AE incidence was 67.1 % with canagliflozin 100 mg , 68.6 % with canagliflozin 300 mg , and 65.9 % with non‐canagliflozin ( pooled group of comparators in all studies ) in participants younger than 75 , and 72.4 % , 79.1 % , and 72.3 % , respectively , in those aged 75 and older , with a similar safety profile in both groups . The incidence of volume depletion – related AEs was 2.2 % , 3.1 % , and 1.4 % in participants younger than 75 with canagliflozin 100 and 300 mg and non‐canagliflozin , respectively , and 4.9 % , 8.7 % , and 2.6 % , respectively , in those aged 75 and older .  Conclusion Canagliflozin improved glycemic control , body weight , and BP in participants aged 75 and older . The overall incidence of AEs was high across treatment groups in participants aged 75 and older and higher than in those younger than 75 . The safety profile of canagliflozin was generally similar in both age groups , with a higher incidence of AEs related to volume depletion observed with canagliflozin in participants aged 75 and older than in those younger than 75 . These findings support canagliflozin , starting with the 100‐mg dose , as an effective therapeutic option for older adults with T2DM OBJECTIVE To analyze the relationships between cardiovascular complications and geriatric scale scores in French elderly ( ≥70 years of age ) type 2 diabetic patients at inclusion in the GERODIAB cohort . RESEARCH DESIGN AND METHODS GERODIAB is the first French multicenter , prospect i ve , observational survey design ed to analyze the influence of glycemic control on morbidity/mortality in type 2 diabetic patients aged ≥70 years during a 5-year follow-up period . This study analyzed the relationships between classical macroangiopathic complications and  geriatric scale scores  in 987 patients at baseline , using bivariate and multivariate analyses . RESULTS Cardiac ischemia ( 31.2 % ) was significantly associated with impaired activities of daily living ( ADL ) scores ( P < 0.001 ) . Stepwise logistic regression included hypercholesterolemia , ADL , sex , and hypertension successively ( 70.3 % concordance ; P < 0.001 ) . Heart failure ( 10.1 % ) was associated with impaired Mini Mental State Examination ( MMSE ) , instrumental ADL ( IADL ) ( P < 0.05 ) , and ADL scores ( P < 0.001 ) . With the logistic model , waist circumference , age , and HDL cholesterol were significant factors ( 70.7 % concordance ; P < 0.001 ) . Arterial disease of the lower limbs ( 25.6 % ) was associated with impaired IADL and ADL scores ( P < 0.001 ) . Significant factors using the logistic model were duration of diabetes , IADL score , hypertension , and sex ( 62.8 % concordance ; P < 0.001 ) . Cerebral ischemia ( 15.8 % ) was associated with impaired MMSE , Mini Nutritional Assessment , ADL , and IADL scores ( P < 0.01 ) . IADL , sex , hypertension , and ADL were included in the logistic model successively ( 65.6 % concordance ; P < 0.001 ) . CONCLUSIONS In this specific population , impaired geriatric scale scores were found to be associated with classical macrovascular complications , notably using multivariate analyses . This suggests the benefits of thorough screening and management of cognitive and functional decline in elderly type 2 diabetic patients Background Diabetes , a highly prevalent , chronic disease , is associated with increasing frailty and functional decline in older people , with concomitant personal , social , and public health implication s. We describe the rationale and methods of the multi-modal intervention in diabetes in frailty ( MID-Frail ) study . Methods / Design The MID-Frail study is an open , r and omised , multicentre study , with r and om allocation by clusters ( each trial site ) to a usual care group or an intervention group . A total of 1,718 subjects will be r and omised with each site enrolling on average 14 or 15 subjects . The primary objective of the study is to evaluate , in comparison with usual clinical practice , the effectiveness of a multi-modal intervention ( specific clinical targets , education , diet , and resistance training exercise )  in frail and pre-frail subjects aged ≥70 years with type 2 diabetes in terms of the difference in function 2 years post-r and omisation . Difference in function will be measured by changes in a summary ordinal score on the short physical performance battery ( SPPB ) of at least one point . Secondary outcomes include daily activities , economic evaluation , and quality of life . Discussion The MID-Frail study will provide evidence on the clinical , functional , social , and economic impact of a multi-modal approach in frail and pre-frail older people with type 2 diabetes . Trial registration Clinical Trials.gov : NCT01654341 Introduction Low-calorie sweetener use for weight control has come under increasing scrutiny as obesity , especially abdominal obesity , remain entrenched despite substantial low-calorie sweetener use . We evaluated whether chronic low-calorie sweetener use is a risk factor for abdominal obesity . Participants and Methods We used 8268 anthropometric measurements and 3096 food diary records with detailed information on low-calorie sweetener consumption in all food products , from 1454 participants ( 741 men , 713 women ) in the Baltimore Longitudinal Study of Aging collected from 1984 to 2012 with median follow-up of 10 years ( range : 0–28 years ) . At baseline , 785 were low-calorie sweetener non-users ( 51.7 % men ) and 669 participants were low-calorie sweetener users ( 50.1 % men ) . Time-varying low-calorie sweetener use was operationalized as the proportion of visits since baseline at which low-calorie sweetener use was reported . We used marginal structural models to determine the association between baseline and time-varying low-calorie sweetener use with longitudinal outcomes —body mass index , waist circumference , obesity and abdominal obesity — with outcome status assessed at the visit following low-calorie sweetener ascertainment to minimize the potential for reverse causality . All models were adjusted for year of visit , age , sex , age by sex interaction , race , current smoking status , dietary intake ( caffeine , fructose , protein , carbohydrate , and fat ) , physical activity , diabetes status , and Dietary Approaches to Stop Hypertension score as confounders . Results With median follow-up of 10 years , low-calorie sweetener users had 0.80 kg/m2 higher body mass index ( 95 % confidence interval [ CI ] , 0.17–1.44 ) , 2.6 cm larger waist circumference ( 95 % CI , 0.71–4.39 ) , 36.7 % higher prevalence ( prevalence ratio = 1.37 ; 95 % CI , 1.10–1.69 ) and 53 % higher incidence ( hazard ratio = 1.53 ; 95 % CI 1.10–2.12 ) of abdominal obesity than low-calorie sweetener non-users . Conclusions Low-calorie sweetener use is independently associated with heavier relative weight , a larger waist , and a higher prevalence and incidence of abdominal obesity suggesting that low-calorie sweetener use may not be an effective means of weight control Background and Aims Few studies have evaluated long-term durability of glycemic control in older patients . The aim of this study was to compare durability of glycemic control of twice-daily insulin lispro mix 75/25 ( LM75/25 ; 75 % insulin lispro protamine suspension , 25 % insulin lispro ) and once-daily insulin glargine ( GL ) added to oral antihyperglycemic medications in older patients ( ≥65 years of age ) . Methods Patients were participants in the maintenance phase of the DURABLE trial . During the initiation phase , patients with type 2 diabetes were r and omized to LM75/25 or GL . After 6 months , patients with hemoglobin A1c ( HbA1c ) ≤7.0 % advanced to the 24-month maintenance phase . The primary objective was between-group comparison of duration of maintaining the HbA1c goal in older patients ( ≥65 years of age ) . A similar analysis was conducted for older patients achieving HbA1c ≤6.5 % in the initiation phase .  Results Median time of maintaining HbA1c goal was longer in LM75/25 versus GL ( 19.6 versus 15.4 months , p = 0.007 ) and more LM75/25 patients maintained goal versus GL ( 49.2 versus 30.4 % ; p = 0.003 ) . HbA1c reduction from baseline was greater in LM75/25 versus GL ( −1.56 ± 0.10 versus −1.24 ± 0.11 % ; p = 0.003 ) . Post-meal glucose was significantly lower in LM75/25 versus GL ( 158.86 ± 3.42 versus 171.67 ± 4.51 mg/dL ; p = 0.017 ) . No differences were observed in overall and severe hypoglycemia . LM75/25 patients had higher daily insulin doses ( 0.41 ± 0.02 versus 0.32 ± 0.02 units/kg/day ; p < 0.001 ) and more weight gain ( 5.47 ± 0.49 versus 3.10 ± 0.53 kg ; p = 0.001 ) . Similar results were generally obtained in older patients with HbA1c ≤6.5 % . Conclusions In our evaluation of older patients from a larger trial , LM75/25 appeared to provide longer durability of glycemic control , as well as a greater number of patients maintaining HbA1c goal versus GL Aims To determine the effects of empagliflozin on blood pressure ( BP ) and markers of arterial stiffness and vascular resistance in patients with type 2 diabetes mellitus ( T2DM ) . Methods We conducted a post hoc analysis of data from a phase III trial in patients with T2DM and hypertension receiving 12 weeks ' empagliflozin and four phase III trials in patients with T2DM receiving 24 weeks ' empagliflozin ( cohort 1 , n = 823 ; cohort 2 , n = 2477 ) . BP was measured using 24‐h BP monitoring ( cohort 1 ) or seated office measurements ( cohort 2 ) . Results Empagliflozin  reduced systolic BP ( SBP ) and diastolic BP in both cohorts ( p < 0.001 vs placebo ) , without increasing heart rate  . Empagliflozin  reduced pulse pressure ( PP ; adjusted mean difference vs placebo cohort 1 : −2.3 mmHg ; cohort 2 : −2.3 mmHg ) , mean arterial pressure ( MAP ; cohort 1 , −2.3 mmHg ; cohort 2 , −2.1 mmHg ) and double product ( cohort 1 , −385 mmHg × bpm ; cohort 2 , −369 mmHg × bpm ) all p < 0.001 vs placebo . There was a trend towards a reduction in the ambulatory arterial stiffness index ( AASI )  with empagliflozin in cohort 1 ( p = 0.059 vs placebo ) . AASI was not measured in cohort 2 . Subgroup analyses showed that there were greater reductions in PP with increasing baseline SBP in cohort 1 ( p = 0.092 ) . In cohort 2 , greater reductions in MAP were achieved in patients with higher baseline SBP ( p = 0.027 ) and greater reductions in PP were observed in older patients ( p = 0.011 ) . Conclusions Empagliflozin  reduced BP and had favourable effects on markers of arterial stiffness and vascular resistance BACKGROUND A substantial proportion of patients with type 2 diabetes are elderly ( ≥65 years ) but this group has been largely excluded from clinical studies of glucose-lowering drugs . We aim ed to assess the effectiveness of linagliptin , a dipeptidyl peptidase-4 inhibitor , in elderly patients with type 2 diabetes . METHODS In this r and omised , double-blind , parallel-group , multinational phase 3 study , patients aged 70 years or older with type 2 diabetes , glycated haemoglobin A1c ( HbA1c ) of 7·0 % or more , receiving metformin , sulfonylureas , or basal insulin , or combinations of these drugs  , were r and omised ( by computer-generated r and omisation sequence , concealed with a voice-response system , stratified by HbA1c level [ < 8·5 % vs ≥8·5 % ] and insulin use [ yes vs no ] , block size four ) in a 2:1 ratio to once-daily oral treatment with linagliptin 5 mg or matching placebo for 24 weeks . Investigators and participants were masked to assignment throughout the study . The primary endpoint was change in HbA1c from baseline to week 24 . This trial is registered with Clinical Trials.gov , number NCT01084005 . FINDINGS 241 community-living out patients were r and omised ( 162 linagliptin , 79 placebo ) . Mean age was 74·9 years ( SD 4·3 ) . Mean HbA1c was 7·8 % ( SD 0·8 ) . At week 24 , placebo-adjusted mean change in HbA1c with linagliptin was -0·64 % ( 95 % CI -0·81 to -0·48 , p<0·0001 ) . Overall safety and tolerability were much the same between the linagliptin and placebo groups ; 75·9 % of patients in both groups had an adverse event ( linagliptin n=123 , placebo n=60 ) . No deaths occurred . Serious adverse events occurred in 8·6 % ( 14 ) of patients in the linagliptin group and 6·3 % ( five ) patients in the placebo group ; none were deemed related to study drug . Hypoglycaemia was the most common adverse event in both groups , but did not differ between groups ( 24·1 % [ 39 ] in the linagliptin group , 16·5 % [ 13 ] in the placebo group ; odds ratio 1·58 , 95 % CI 0·78 - 3·78 , p=0·2083 ) . INTERPRETATION In elderly patients with type 2 diabetes linagliptin was efficacious in lowering glucose with a safety profile similar to placebo . These findings could inform treatment decisions for achieving individualised glycaemic goals with minimal risk in this important population of patients . FUNDING Boehringer Ingelheim Objective The aim of this study was to evaluate the safety and tolerability of sitagliptin 100 mg/day in elderly patients with type 2 diabetes . Design A post hoc pooled analysis of 25 r and omized , double-blind , parallel group clinical studies with results available as of 1 December 2011 . Setting Multicenter , international clinical trials . Subjects Patients with type 2 diabetes aged 65 years or older . Interventions Patients were r and omized to sitagliptin 100 mg/day ( n = 1,261 ) or a comparator ( n = 1,185 ) for 12 weeks to 2 years . Main Outcome Measures In each study , investigators reported serious and non-serious adverse events that occurred during the study , and serious adverse events occurring within 14 days following the last dose of study drug . This analysis used patient-level data from each study to assess the exposure-adjusted incidence rates of specific adverse events that occurred following initiation of study drug . Results Summary measures of adverse events overall were similar between the sitagliptin and non-exposed ( active comparator or placebo ) groups , except for higher incidences of deaths and drug-related adverse events in the non-exposed group . Incidence rates of specific adverse events were generally similar between the two groups , with the exception of hypoglycemia . A lower incidence rate of hypoglycemia was observed in the sitagliptin group compared with the non-exposed group [ 7.0 vs. 14.3 per 100 patient-years ; difference −7.6 ( 95 % CI −11.2 to −4.3 ] ) , primarily due to greater use of sulfonylureas in the non-exposed group . Conclusions In this pooled safety analysis of elderly patients with type 2 diabetes , treatment with sitagliptin 100 mg/day was generally well tolerated for up to 2 years Objective To examine whether established diabetes risk factors and diabetes risk algorithms are associated with future frailty . Design Prospect i ve cohort study . Risk algorithms at baseline ( 1997–1999 ) were the Framingham Offspring , Cambridge , and Finnish diabetes risk scores . Setting Civil service departments in London , United Kingdom . Participants There were 2707 participants ( 72 % men ) aged 45 to 69 years at baseline assessment and free of diabetes . Measurements Risk factors ( age , sex , family history of diabetes , body mass index , waist circumference , systolic and diastolic blood pressure , antihypertensive and corticosteroid treatments , history of high blood glucose , smoking status , physical activity , consumption of fruits and vegetables , fasting glucose , HDL-cholesterol , and triglycerides ) were used to construct the risk algorithms . Frailty , assessed during a resurvey in 2007–2009 , was denoted by the presence of 3 or more of the following indicators : self-reported exhaustion , low physical activity , slow walking speed , low grip strength , and weight loss ; “ prefrailty ” was defined as having 2 or fewer of these indicators . Results After a mean follow-up of 10.5 years , 2.8 % of the sample was classified as frail and 37.5 % as prefrail . Increased age , being female , stopping smoking , low physical activity , and not having a daily consumption of fruits and vegetables were each associated with frailty or prefrailty . The Cambridge and Finnish diabetes risk scores were associated with frailty/prefrailty with odds ratios per 1 SD increase ( disadvantage ) in score of 1.18 ( 95 % confidence interval : 1.09–1.27 ) and 1.27 ( 1.17–1.37 ) , respectively . Conclusion Selected diabetes risk factors and risk scores are associated with subsequent frailty . Risk scores may have utility for frailty prediction in clinical practice The sustainability of health and social care systems is threatened by a growing population of older persons with heterogeneous needs related to multimorbidity , frailty , and increased risk of functional impairment . Since disability is difficult to reverse in old age and is extremely burdensome for individuals and society , novel strategies should be devised to preserve adequate levels of function and independence in late life . The development of mobility disability , an early event in the disablement process , precedes and predicts more severe forms of inability . Its prevention is , therefore , critical to impede the transition to overt disability . For this reason , the Sarcopenia and Physical fRailty IN older people : multi-componenT Treatment strategies ( SPRINTT ) project is conducting a r and omized controlled trial ( RCT ) to test a multicomponent intervention ( MCI ) specifically design ed to prevent mobility disability in high-risk older persons . SPRINTT is a phase III , multicenter RCT aim ed at comparing the efficacy of a MCI , based on long-term structured physical activity , nutritional counseling/dietary intervention , and an information and communication technology intervention , versus a healthy aging lifestyle education program design ed to prevent mobility disability in 1500 older persons with physical frailty and sarcopenia who will be followed for up to 36 months . The primary outcome of the SPRINTT trial is mobility disability , operationalized as the inability to walk for 400 m within 15 min , without sitting , help of another person , or the use of a walker . Secondary outcomes include changes in muscle mass and strength , persistent mobility disability , falls and injurious falls , disability in activities of daily living , nutritional status , cognition , mood , the use of healthcare re sources , cost-effectiveness analysis , quality of life , and mortality rate . SPRINTT results are expected to promote significant advancements in the management of frail older persons at high risk of disability from both clinical and regulatory perspectives . The findings are also projected to pave the way for major investments in the field of disability prevention in old age AIMS The GERODIAB study is the first French multicentre , prospect i ve , observational study that aims , through a 5-year cohort follow-up , to evaluate the link between glycaemic control and morbidity/mortality of type 2 diabetic ( T2D ) patients aged 70 years and older . This first report describes the study population at inclusion . PATIENTS AND METHODS A total of 987 T2D autonomous patients , aged ≥70 years , were recruited between June 2009 and July 2010 at 56 investigator centres . Their general parameters , diabetes characteristics and st and ard geriatric parameters were recorded . RESULTS The patients ' mean age was 77±5 years , with 65.2 % aged 75 years or more . The mean BMI was close to 30 kg/m(2 ) . Hypertension was found in 89.7 % of patients , and 85.0 % had at least one cholesterol abnormality . The mean duration of the diabetes was around 18 years , and the mean HbA(1c ) level was about 7.5 % . During the previous six months , 33.6 % of patients had experienced one or several hypoglycaemias . Also , 26 % of patients presented with diabetic retinopathy , 37.3 % had a GFR<60 mL/min , 31.2 % had coronary insufficiency , 10.1 % had heart failure , 15.8 % had cerebrovascular involvement and 25.6 % had peripheral vascular disease of the lower extremities . In addition , 30.5 % of patients had orthostatic hypotension , 12.4 % had malnutrition and 28.8 % had cognitive impairment , all of which were often diagnosed at inclusion . Three-quarters of patients were taking an oral antidiabetic drug and nearly six in every 10 patients were using insulin . CONCLUSION This population can be considered representative of elderly , autonomous T2D patients , and its follow-up should clarify the link between glycaemic control and mortality/morbidity Aims To compare the efficacy and safety of new insulin glargine 300 U/ml ( Gla-300 ) with that of glargine 100 U/ml ( Gla-100 ) in insulin-naïve people with type 2 diabetes using oral glucose-lowering drugs . Methods The EDITION 3 study was a multicentre , open-label , parallel-group study . Participants were r and omized to Gla-300 or Gla-100 once daily for 6 months , discontinuing sulphonylureas and glinides , with a dose titration aim ed at achieving pre-breakfast plasma glucose concentrations of 4.4–5.6 mmol/l ( 80–100 mg/dl ) . The primary endpoint was change in glycated haemoglobin ( HbA1c ) from baseline to month 6 . The main secondary endpoint was percentage of participants with ≥1 nocturnal confirmed [ ≤3.9 mmol/l ( ≤70 mg/dl ) ] or severe hypoglycaemia from week 9 to month 6 . Other measures of glycaemia and hypoglycaemia , weight change and insulin dose were assessed . Results R and omized participants ( n = 878 ) had a mean ( st and ard deviation ) age of 57.7 ( 10.1 ) years , diabetes duration 9.8 ( 6.4 ) years , body mass index 33.0 ( 6.7 ) kg/m2 and HbA1c 8.54 ( 1.06 ) % [ 69.8 ( 11.6 ) mmol/mol ] . HbA1c levels decreased by equivalent amounts with the two treatments ; the least squares mean difference in change from baseline was 0.04 [ 95 % confidence interval ( CI ) −0.09 to 0.17 ] % or 0.4 ( −1.0 to 1.9 ) mmol/mol . Numerically fewer participants reported ≥1 nocturnal confirmed ( ≤3.9 mmol/l ) or severe hypoglycaemia from week 9 to month 6 [ relative risk ( RR ) 0.89 ( 95 % CI 0.66 to 1.20 ) ] with Gla-300 versus Gla-100 ; a significantly lower risk of hypoglycaemia with this definition was found over the 6-month treatment period [ RR 0.76 ( 95 % CI 0.59 to 0.99 ) ] . No between-treatment differences in adverse events were identified . Conclusions Gla-300 is as effective as Gla-100 in reducing HbA1c in insulin-naïve people with type 2 diabetes , with lower hypoglycaemia risk ABSTRACT Accumulating evidence implicates gut microbiota as promising targets for the treatment of type 2 diabetes mellitus ( T2DM ) . With a r and omized clinical trial , we tested the hypothesis that alteration of gut microbiota may be involved in the alleviation of T2DM with hyperlipidemia by metformin and a specifically design ed herbal formula ( AMC ) .  Four hundred fifty patients with T2DM and hyperlipidemia were r and omly assigned to either the metformin- or AMC-treated group . After 12 weeks of treatment , 100 patients were r and omly selected from each group and assessed for clinical improvement . The effects of the two drugs on the intestinal microbiota were evaluated by analyzing the V3 and V4 regions of the 16S rRNA gene by Illumina sequencing and multivariate statistical methods . Both metformin and AMC significantly alleviated hyperglycemia and hyperlipidemia and shifted gut microbiota structure in diabetic patients . They significantly increased a coabundant group represented by Blautia spp . , which significantly correlated with the improvements in glucose and lipid homeostasis . However , AMC showed better efficacies in improving homeostasis model assessment of insulin resistance ( HOMA-IR ) and plasma triglyceride and also exerted a larger effect on gut microbiota . Furthermore , only AMC increased the coabundant group represented by Faecalibacterium spp . , which was previously reported to be associated with the alleviation of T2DM in a r and omized clinical trial . Metformin and the Chinese herbal formula may ameliorate type 2 diabetes with hyperlipidemia via enriching beneficial bacteria , such as Blautia and Faecalibacterium spp . IMPORTANCE Metabolic diseases such as T2DM and obesity have become a worldwide public health threat . Accumulating evidence indicates that gut microbiota can causatively arouse metabolic diseases , and thus the gut microbiota serves as a promising target for disease control . In this study , we evaluated the role of gut microbiota during improvements in hyperglycemia and hyperlipidemia by two drugs : metformin and a specifically design ed Chinese herbal formula ( AMC ) for diabetic patients with hyperlipidemia . Both drugs significantly ameliorated blood glucose and lipid levels and shifted the gut microbiota . Blautia spp . were identified as being associated with improvements in glucose and lipid homeostasis for both drugs . AMC exerted larger effects on the gut microbiota together with better efficacies in improving HOMA-IR and plasma triglyceride levels , which were associated with the enrichment of Faecalibacterium spp . In brief , these data suggest that gut microbiota might be involved in the alleviation of diabetes with hyperlipidemia by metformin and the AMC herbal formula . Metabolic diseases such as T2DM and obesity have become a worldwide public health threat . Accumulating evidence indicates that gut microbiota can causatively arouse metabolic diseases , and thus the gut microbiota serves as a promising target for disease control . In this study , we evaluated the role of gut microbiota during improvements in hyperglycemia and hyperlipidemia by two drugs : metformin and a specifically design ed Chinese herbal formula ( AMC ) for diabetic patients with hyperlipidemia . Both drugs significantly ameliorated blood glucose and lipid levels and shifted the gut microbiota . Blautia spp . were identified as being associated with improvements in glucose and lipid homeostasis for both drugs . AMC exerted larger effects on the gut microbiota together with better efficacies in improving HOMA-IR and plasma triglyceride levels , which were associated with the enrichment of Faecalibacterium spp . In brief , these data suggest that gut microbiota might be involved in the alleviation of diabetes with hyperlipidemia by metformin and the AMC herbal formula BACKGROUND For patients with type 2 diabetes who do not achieve target glycaemic control with conventional insulin treatment , advancing to a basal-bolus insulin regimen is often recommended . We aim ed to compare the efficacy and safety of long-acting glucagon-like peptide-1 receptor agonist dulaglutide with that of insulin glargine , both combined with pr and ial insulin lispro , in patients with type 2 diabetes . METHODS We did this 52 week , r and omised , open-label , phase 3 , non-inferiority trial at 105 study sites in 15 countries . Patients ( aged ≥18 years ) with type 2 diabetes inadequately controlled with conventional insulin treatment were r and omly assigned ( 1:1:1 ) , via a computer-generated r and omisation sequence with an interactive voice-response system , to receive once-weekly dulaglutide 1·5 mg , dulaglutide 0·75 mg , or daily bedtime glargine . R and omisation was stratified by country and metformin use . Participants and study investigators were not masked to treatment allocation , but were unaware of dulaglutide dose assignment . The primary outcome was a change in glycated haemoglobin A1c ( HbA1c ) from baseline to week 26 , with a 0·4 % non-inferiority margin . Analysis was by intention to treat . This trial is registered with Clinical Trials.gov , number NCT01191268 . FINDINGS Between Dec 9 , 2010 , and Sept 21 , 2012 , we r and omly assigned 884 patients to receive dulaglutide 1·5 mg ( n=295 ) , dulaglutide 0·75 mg ( n=293 ) , or glargine ( n=296 ) . At 26 weeks , the adjusted mean change in HbA1c was greater in patients receiving dulaglutide 1·5 mg ( -1·64 % [ 95 % CI -1·78 to -1·50 ] , -17·93 mmol/mol [ -19·44 to -16·42 ] ) and dulaglutide 0·75 mg ( -1·59 % [ -1·73 to -1·45 ] , -17·38 mmol/mol [ -18·89 to -15·87 ] ) than in those receiving glargine ( -1·41 % [ -1·55 to -1·27 ] , -15·41 mmol/mol [ -16·92 to -13·90 ] ) . The adjusted mean difference versus glargine was -0·22 % ( 95 % CI -0·38 to -0·07 , -2·40 mmol/mol [ -4·15 to -0·77 ] ; p=0·005 ) for dulaglutide 1·5 mg and -0·17 % ( -0·33 to -0·02 , -1·86 mmol/mol [ -3·61 to -0·22 ] ; p=0·015 ) for dulaglutide 0·75 mg . Five ( < 1 % ) patients died after r and omisation because of septicaemia ( n=1 in the dulaglutide 1·5 mg group ) ; pneumonia ( n=1 in the dulaglutide 0·75 mg group ) ; cardiogenic shock ; ventricular fibrillation ; and an unknown cause ( n=3 in the glargine group ) . We recorded serious adverse events in 27 ( 9 % ) patients in the dulaglutide 1·5 mg group , 44 ( 15 % ) patients in the dulaglutide 0·75 mg group , and 54 ( 18 % ) patients in the glargine group . The most frequent adverse events , arising more often with dulaglutide than glargine , were nausea , diarrhoea , and vomiting . INTERPRETATION Dulaglutide in combination with lispro result ed in a significantly greater improvement in glycaemic control than did glargine and represents a new treatment option for patients unable to achieve glycaemic targets with conventional insulin treatment . FUNDING Eli Lilly and Company Background : Dapagliflozin is a sodium‐glucose co‐transporter‐2 ( SGLT‐2 ) inhibitor that reduces blood glucose in patients with type 2 diabetes mellitus ( T2DM ) by promoting glycosuria via inhibiting urinary glucose reabsorption . In addition to improving blood glucose control , treatment with dapagliflozin results in glucose‐induced osmotic diuresis , weight loss , and blood pressure lowering . Previous trials of SGLT‐2 inhibitors showed reductions in cardiovascular ( CV ) events , including CV death and hospitalization for heart failure , and ischemic events in patients with atherosclerotic cardiovascular disease ( ASCVD ) . Research design and methods : DECLARE – TIMI 58 ( NCT01730534 ) is a phase 3b r and omized , double‐blind , placebo‐controlled trial design ed to evaluate the CV safety and efficacy of dapagliflozin that has completed r and omization of 17,160 patients with T2DM and a history of either established ASCVD ( n = 6,971 ) or multiple risk factors for ASCVD ( n = 10,189 ) . Patients were r and omized in a 1:1 fashion to dapagliflozin 10 mg or matching placebo . The primary safety outcome is the time to the first event of the composite of CV death , myocardial infa rct ion , or ischemic stroke ( major adverse cardiovascular events ; MACEs ) . The co‐ primary efficacy outcomes are the composite of CV death , myocardial infa rct ion , or ischemic stroke and the composite of CV death or hospitalization for heart failure . This event‐driven trial will continue until at least 1,390 subjects have a MACE outcome , thereby providing > 99 % power to test for the primary outcome of safety  of dapagliflozin measured by rejecting the hypothesis that the upper bound of the CI > 1.3 for the primary outcome of MACE , as well as 85 % power to detect a 15 % relative risk reduction in MACE and an estimated 87 % power to detect a 20 % reduction in the composite of CV death or hospitalization for heart failure at a 1‐sided & agr ; level of .0231 . Conclusion : The DECLARE – TIMI 58 trial is testing the hypotheses that dapagliflozin is safe ( does not increase ) and may reduce the occurrence of major CV events . DECLARE – TIMI 58 is the largest study to address this question with an SGLT‐2 inhibitor in patients with T2DM and with established CV disease and without CV disease but with multiple risk factors AIMS To assess initial pharmacotherapy of Type 2 diabetes with the sodium-glucose cotransporter-2 inhibitor dapagliflozin . METHODS This double-blind , placebo-controlled trial , r and omly allocated people with Type 2 diabetes aged 18 - 77 years and inadequate glycaemic control on diet and exercise [ HbA1c 53 - 86 mmol/mol ( 7.0 - 10.0 % ) ] to receive placebo ( n = 75 ) or dapagliflozin monotherapy 2.5 mg ( n = 65 ) , 5 mg ( n = 64 ) or 10 mg ( n = 70 ) once daily in the morning . After 24 weeks , low-dose double-blind metformin 500 mg/day was added to the placebo group regimen ( placebo+low-dose metformin group ) . Changes in HbA1c level , fasting plasma glucose and body weight , as well as adverse events , were assessed over 102 weeks . RESULTS Of the 274 participants r and omized , 167 completed the study ( 60.9 % ) . At 102 weeks , significant differences vs placebo+low-dose metformin with dapagliflozin 5 and 10 mg were observed for HbA1c ( -5.8 mmol/mol [ -0.53 % ] , P = 0.018 ; and -4.8 mmol/mol [ -0.44 % ] , P = 0.048 ) , respectively ) ; and for FPG ( -0.69 mmol/L , P = 0.044 ; and -1.12 mmol/l , P = 0.001 , respectively ) . For body weight , the difference between the dapagliflozin 10-mg group and the placebo+low-dose metformin group was significant ( -2.60 kg ; P = 0.016 ) . Hypoglycaemic events were uncommon , with rates of 5.3 % for placebo+low-dose metformin group and 0 - 4.6 % for the dapagliflozin groups . Genital infections and urinary tract infections were more common in the dapagliflozin groups than in the placebo+low-dose metformin group . CONCLUSIONS Dapagliflozin as monotherapy in treatment-naïve people with early Type 2 diabetes improved glycaemic control and reduced weight without increasing hypoglycaemia over 102 weeks . Dapagliflozin may provide an alternative initial pharmacotherapy in such people BACKGROUND The effects of empagliflozin , an inhibitor of sodium-glucose cotransporter 2 , in addition to st and ard care , on cardiovascular morbidity and mortality in patients with type 2 diabetes at high cardiovascular risk are not known . METHODS We r and omly assigned patients to receive 10 mg or 25 mg of empagliflozin or placebo once daily . The primary composite outcome was death from cardiovascular causes , nonfatal myocardial infa rct ion , or nonfatal stroke , as analyzed in the pooled empagliflozin group versus the placebo group . The key secondary composite outcome was the primary outcome plus hospitalization for unstable angina . RESULTS A total of 7020 patients were treated ( median observation time , 3.1 years ) . The primary outcome occurred in 490 of 4687 patients ( 10.5 % ) in the pooled empagliflozin group and in 282 of 2333 patients ( 12.1 % ) in the placebo group ( hazard ratio in the empagliflozin group , 0.86 ; 95.02 % confidence interval , 0.74 to 0.99 ; P=0.04 for superiority ) . There were no significant between-group differences in the rates of myocardial infa rct ion or stroke , but in the empagliflozin group there were significantly lower rates of death from cardiovascular causes ( 3.7 % , vs. 5.9 % in the placebo group ; 38 % relative risk reduction ) , hospitalization for heart failure ( 2.7 % and 4.1 % , respectively ; 35 % relative risk reduction ) , and death from any cause ( 5.7 % and 8.3 % , respectively ; 32 % relative risk reduction ) . There was no significant between-group difference in the key secondary outcome ( P=0.08 for superiority ) . Among patients receiving empagliflozin , there was an increased rate of genital infection but no increase in other adverse events . CONCLUSIONS Patients with type 2 diabetes at high risk for cardiovascular events who received empagliflozin , as compared with placebo , had a lower rate of the primary composite cardiovascular outcome and of death from any cause when the study drug was added to st and ard care . ( Funded by Boehringer Ingelheim and Eli Lilly ; EMPA-REG OUTCOME Clinical Trials.gov number , NCT01131676 . ) BACKGROUND Cardiovascular morbidity and mortality are higher among patients with type 2 diabetes , particularly those with concomitant cardiovascular diseases , than in most other population s. We assessed the effects of lixisenatide , a glucagon-like peptide 1-receptor agonist , on cardiovascular outcomes in patients with type 2 diabetes who had had a recent acute coronary event . METHODS We r and omly assigned patients with type 2 diabetes who had had a myocardial infa rct ion or who had been hospitalized for unstable angina within the previous 180 days to receive lixisenatide or placebo in addition to locally determined st and ards of care . The trial was design ed with adequate statistical power to assess whether lixisenatide was noninferior as well as superior to placebo , as defined by an upper boundary of the 95 % confidence interval for the hazard ratio of less than 1.3 and 1.0 , respectively , for the primary composite end point of cardiovascular death , myocardial infa rct ion , stroke , or hospitalization for unstable angina . RESULTS The 6068 patients who underwent r and omization were followed for a median of 25 months . A primary end-point event occurred in 406 patients ( 13.4 % ) in the lixisenatide group and in 399 ( 13.2 % ) in the placebo group ( hazard ratio , 1.02 ; 95 % confidence interval [ CI ] , 0.89 to 1.17 ) , which showed the noninferiority of lixisenatide to placebo ( P<0.001 ) but did not show superiority ( P=0.81 ) . There were no significant between-group differences in the rate of hospitalization for heart failure ( hazard ratio in the lixisenatide group , 0.96 ; 95 % CI , 0.75 to 1.23 ) or the rate of death ( hazard ratio , 0.94 ; 95 % CI , 0.78 to 1.13 ) . Lixisenatide was not associated with a higher rate of serious adverse events or severe hypoglycemia , pancreatitis , pancreatic neoplasms , or allergic reactions than was placebo . CONCLUSIONS In patients with type 2 diabetes and a recent acute coronary syndrome , the addition of lixisenatide to usual care did not significantly alter the rate of major cardiovascular events or other serious adverse events . ( Funded by Sanofi ; ELIXA Clinical Trials.gov number , NCT01147250 . ) Background Canagliflozin is a sodium – glucose cotransporter 2 inhibitor that reduces glycemia as well as blood pressure , body weight , and albuminuria in people with diabetes . We report the effects of treatment with canagliflozin on cardiovascular , renal , and safety outcomes . Methods The CANVAS Program integrated data from two trials involving a total of 10,142 participants with type 2 diabetes and high cardiovascular risk . Participants in each trial were r and omly assigned to receive canagliflozin or placebo and were followed for a mean of 188.2 weeks . The primary outcome was a composite of death from cardiovascular causes , nonfatal myocardial infa rct ion , or nonfatal stroke . Results The mean age of the participants was 63.3 years , 35.8 % were women , the mean duration of diabetes was 13.5 years , and 65.6 % had a history of cardiovascular disease .  The rate of the primary outcome was lower with canagliflozin than with placebo ( occurring in 26.9 vs. 31.5 participants per 1000 patient‐years ; hazard ratio , 0.86 ; 95 % confidence interval [ CI ] , 0.75 to 0.97 ; P<0.001 for noninferiority ; P=0.02 for superiority ) . Although on the basis of the prespecified hypothesis testing sequence the renal outcomes are not viewed as statistically significant , the results showed a possible benefit of canagliflozin with respect to the progression of albuminuria ( hazard ratio , 0.73 ; 95 % CI , 0.67 to 0.79 ) and the composite outcome of a sustained 40 % reduction in the estimated glomerular filtration rate , the need for renal‐replacement therapy , or death from renal causes ( hazard ratio , 0.60 ; 95 % CI , 0.47 to 0.77 ) . Adverse reactions were consistent with the previously reported risks associated with canagliflozin except for an increased risk of amputation ( 6.3 vs. 3.4 participants per 1000 patient‐years ; hazard ratio , 1.97 ; 95 % CI , 1.41 to 2.75 ) ; amputations were primarily at the level of the toe or metatarsal . Conclusions In two trials involving patients with type 2 diabetes and an elevated risk of cardiovascular disease , patients treated with canagliflozin had a lower risk of cardiovascular events than those who received placebo but a greater risk of amputation , primarily at the level of the toe or metatarsal . ( Funded by Janssen Research and Development ; CANVAS and CANVAS‐R Clinical Trials.gov numbers , NCT01032629 and NCT01989754 , respectively . BACKGROUND Obesity causes frailty in older adults ; however , weight loss might accelerate age‐related loss of muscle and bone mass and result ant sarcopenia and osteopenia . METHODS In this clinical trial involving 160 obese older adults , we evaluated the effectiveness of several exercise modes in reversing frailty and preventing reduction in muscle and bone mass induced by weight loss . Participants were r and omly assigned to a weight‐management program plus one of three exercise programs — aerobic training , resistance training , or combined aerobic and resistance training — or to a control group ( no weight‐management or exercise program ) . The primary outcome was the change in Physical Performance Test score from baseline to 6 months ( scores range from 0 to 36 points ; higher scores indicate better performance ) . Secondary outcomes included changes in other frailty measures , body composition , bone mineral density , and physical functions . RESULTS A total of 141 participants completed the study .  The Physical Performance Test score increased more in the combination group than in the aerobic and resistance groups ( 27.9 to 33.4 points [ 21 % increase ] vs. 29.3 to 33.2 points [ 14 % increase ] and 28.8 to 32.7 points [ 14 % increase ] , respectively ; P=0.01 and P=0.02 after Bonferroni correction ) ; the scores increased more in all exercise groups than in the control group ( P<0.001 for between‐group comparisons ) . Peak oxygen consumption ( milliliters per kilogram of body weight per minute ) increased more in the combination and aerobic groups ( 17.2 to 20.3 [ 17 % increase ] and 17.6 to 20.9 [ 18 % increase ] , respectively ) than in the resistance group ( 17.0 to 18.3 [ 8 % increase ] ) ( P<0.001 for both comparisons ) . Strength increased more in the combination and resistance groups ( 272 to 320 kg [ 18 % increase ] and 288 to 337 kg [ 19 % increase ] , respectively ) than in the aerobic group ( 265 to 270 kg [ 4 % increase ] ) ( P<0.001 for both comparisons ) . Body weight decreased by 9 % in all exercise groups but did not change significantly in the control group . Lean mass decreased less in the combination and resistance groups than in the aerobic group ( 56.5 to 54.8 kg [ 3 % decrease ] and 58.1 to 57.1 kg [ 2 % decrease ] , respectively , vs. 55.0 to 52.3 kg [ 5 % decrease ] ) , as did bone mineral density at the total hip ( grams per square centimeter ; 1.010 to 0.996 [ 1 % decrease ] and 1.047 to 1.041 [ 0.5 % decrease ] , respectively , vs. 1.018 to 0.991 [ 3 % decrease ] ) ( P<0.05 for all comparisons ) . Exercise‐related adverse events included musculoskeletal injuries . CONCLUSIONS Of the methods tested , weight loss plus combined aerobic and resistance exercise was the most effective in improving functional status of obese older adults . ( Funded by the National Institutes of Health ; LITOE Clinical Trials.gov number , NCT01065636 . BACKGROUND There is emerging evidence of the role of diabetes as a risk factor for frailty . However , the mechanisms of this association are uncertain . METHODS Prospect i ve cohort study of 1750 noninstitutionalized individuals aged 60 years or older recruited in 2008 - 2010 . At baseline , information was obtained on health behaviors , morbidity , cardiometabolic biomarkers , and antidiabetic treatments .  Individuals were considered diabetic if they reported a physician diagnosis or had fasting serum glucose of 126 mg/dL or higher . Study participants were followed through 2012 to assess incident frailty , defined as at least 3 of the 5 Fried criteria . RESULTS At baseline , the cohort included 346 individuals with diabetes and 1404 without diabetes . Over a mean 3.5-year follow-up , 115 cases of incident frailty were ascertained . After adjustment for age , sex , and education , participants with diabetes showed an increased risk of frailty ( odds ratio [ OR ] 2.18 , 95 % confidence interval [ CI ] 1.42 - 3.37 ) . Additional adjustment for health behaviors and abdominal obesity yielded a 29.7 % reduction in the OR ( OR 1.83 , 95 % CI 1.16 - 2.90 ) . Subsequent adjustment for morbidity produced an additional 8.4 % reduction ( OR 1.76 , 95 % CI 1.10 - 2.82 ) , and for cardiometabolic biomarkers , a further 44 % reduction ( OR 1.32 , 95 % CI 0.70 - 2.49 ) . In particular , adjustment for HbA1c , lipoproteins , and triglycerides accounted for the greatest reductions . Finally , additional adjustment for oral antidiabetic medication reduced the OR to 1.01 ( 95 % CI 0.46 - 2.20 ) , whereas adjustment for nutritional therapy increased the OR to 1.64 ( 95 % CI 0.77 - 3.49 ) . CONCLUSIONS Diabetes mellitus is associated with higher risk of frailty ; this association is partly explained by unhealthy behaviors and obesity and , to a greater extent , by poor glucose control and altered serum lipid profile among diabetic individuals . Conversely , diabetes nutritional therapy reduces the risk of frailty OBJECTIVE To compare the efficacy and safety of new insulin glargine 300 units/mL ( Gla-300 ) with glargine 100 units/mL ( Gla-100 ) in people with type 2 diabetes using basal insulin ( ≥42 units/day ) plus oral antihyperglycemic drugs ( OADs ) . RESEARCH DESIGN AND METHODS EDITION 2 was a multicenter , open-label , two-arm study . Adults receiving basal insulin plus OADs were r and omized  to Gla-300 or Gla-100 once daily for 6 months . The primary end point was change in HbA1c . The main secondary end point was percentage of participants with one or more nocturnal confirmed ( ≤3.9 mmol/L [ ≤70 mg/dL ] ) or severe hypoglycemic events from week 9 to month 6 . RESULTS R and omized participants ( n = 811 ) had a mean ( SD ) HbA1c of 8.24 % ( 0.82 ) and BMI of 34.8 kg/m2 ( 6.4 ) . Glycemic control improved similarly with both basal insulins ; least squares mean ( SD ) reduction from baseline was −0.57 % ( 0.09 ) for Gla-300 and −0.56 % ( 0.09 ) for Gla-100 ( mean difference −0.01 % [ 95 % CI −0.14 to 0.12 ] ) , with 10 % higher dose of Gla-300 . Less nocturnal confirmed ( ≤3.9 mmol/L [ ≤70 mg/dL ] ) or severe hypoglycemia was observed with Gla-300 from week 9 to month 6 ( relative risk 0.77 [ 95 % CI 0.61–0.99 ] ; P = 0.038 ) and during the first 8 weeks . Fewer nocturnal and any time ( 24 h ) hypoglycemic events were reported during the entire 6-month period . Weight gain was lower with Gla-300 than with Gla-100 ( P = 0.015 ) . No between-treatment differences in safety parameters were identified . CONCLUSIONS Gla-300 was as effective as Gla-100 and associated with a lower risk of hypoglycemia during the night and at any time of the day Background : Canagliflozin is a sodium glucose cotransporter 2 inhibitor that significantly reduces the composite of cardiovascular death , nonfatal myocardial infa rct ion , or nonfatal stroke in patients with type 2 diabetes mellitus and elevated cardiovascular risk . The comparative effects among participants with and without a history of cardiovascular disease ( secondary versus primary prevention ) were prespecified for evaluation . Methods : The CANVAS Program ( Canagliflozin Cardiovascular Assessment Study ) r and omly assigned 10 142 participants with type 2 diabetes mellitus to canagliflozin or placebo . The primary prevention cohort comprised individuals ≥50 years of age with ≥2 risk factors for cardiovascular events but with no prior cardiovascular event , and the secondary prevention cohort comprised individuals ≥30 years of age with a prior cardiovascular event . The primary end point was a composite of cardiovascular death , nonfatal myocardial infa rct ion , or nonfatal stroke . Secondary outcomes included heart failure hospitalization and a renal composite ( 40 % reduction in estimated glomerular filtration rate , renal replacement therapy , or renal death ) . Results : Primary prevention participants ( N=3486 ; 34 % ) were younger ( 63 versus 64 years of age ) , were more often female ( 45 % versus 31 % ) , and had a longer duration of diabetes mellitus ( 14 versus 13 years ) compared with secondary prevention participants ( N=6656 ; 66 % ) . The primary end point event rate was higher in the secondary prevention group compared with the primary prevention group ( 36.9 versus 15.7/1000 patient-years , P<0.001 ) . In the total cohort , the primary end point was reduced with canagliflozin compared with placebo ( 26.9 versus 31.5/1000 patient-years ; hazard ratio [ HR ] , 0.86 ; 95 % confidence interval [ CI ] , 0.75–0.97 ; P<0.001 for noninferiority , P=0.02 for superiority ) with no statistical evidence of heterogeneity ( interaction P value=0.18 ) between the primary ( HR , 0.98 ; 95 % CI , 0.74–1.30 ) and secondary prevention ( HR , 0.82 ; 95 % CI , 0.72–0.95 ) cohorts . Renal outcomes ( HR , 0.59 ; 95 % CI , 0.44–0.79 versus HR , 0.63 ; 95 % CI , 0.39–1.02 ; interaction P value=0.73 ) and heart failure hospitalization ( HR , 0.68 ; 95 % CI , 0.51–0.90 versus HR , 0.64 ; 95 % CI , 0.35–1.15 ; interaction P value=0.91 ) were similarly reduced in the secondary and primary prevention cohorts , respectively . Lower extremity amputations were similarly increased in the secondary and primary prevention cohorts ( HR , 2.07 ; 95 % CI , 1.43–3.00 versus HR , 1.52 ; 95 % CI , 0.70–3.29 ; interaction P value=0.63 ) . Conclusions : Patients with type 2 diabetes mellitus and prior cardiovascular events had higher rates of cardiovascular outcomes compared with the primary prevention patients .  Canagliflozin reduced cardiovascular and renal outcomes with no statistical evidence of heterogeneity of the treatment effect across the primary and secondary prevention groups . Additional studies will provide further insights into the effects of canagliflozin in these patient population s. Clinical Trial Registration : URL : https://www . clinical trials.gov . Unique identifiers : NCT01032629 and NCT01989754
target: Telemedicine interventions can improve communication and connection between older patients and their providers , and improve glycemic control .
  Summary A systematic review confirmed the efficacy and safety of metformin as first-line therapy of type 2 diabetes in the older adult , but multiple reports highlighted the risk for vitamin B12 deficiency .
  R and omized controlled trials showed the efficacy and safety of antihyperglycemic agents in the elderly , including some with longer duration and lesser risk for hypoglycemia .
  R and omized clinical trials showed cardiovascular protection with SGLT-2i ( empagliflozin , canagliflozin ) and GLP-1RA ( liraglutide , semaglutide ) .
background: Purpose of Review The current approach to diabetes in the elderly incorporates components from the comprehensive geriatric approach .
  The most up date d guidelines from the American Diabetes Association reflect influence from the consensus made in 2012 with the American Geriatrics Society .
  Notably , the framework included the evaluation for geriatric syndromes ( falls and urinary incontinence ) , functional and cognitive abilities .
  The goal for this review is to provide an up date d summary of treatment strategies for community-dwelling older adults .
  Recent Findings Findings on cardiovascular protection with sodium-glucose co-transporter 2 inhibitors ( SGLT-2i ) and some glucagon-like peptide 1 receptor agonists ( GLP-1RA ) support their use for older patients with diabetes .
  Functional medicine concepts can offer additional adjuvant strategies to support the therapeutic interventions and management of diabetes in the elderly .
  The most current guidelines recommend addressing for geriatric syndromes , physical and cognitive function in the elderly , in order to individualize targets and therapeutic strategies .