Effects of alpha-glucosidase inhibitor (acarbose) combined with sulfonylurea or sulfonylurea and metformin in treatment of non-insulin-dependent diabetes mellitus. Acarbose for the treatment of type II diabetes: the results of a Canadian multi-centre trial. Effectiveness of acarbose, an alpha-glucosidase inhibitor, in uncontrolled non-obese non-insulin dependent diabetes. Advantages of alpha-glucosidase inhibition as monotherapy in elderly type 2 diabetic patients. [Evaluation of acarbose efficacy and safety for treatment of diabetes mellitus. Testing of observations under general health care conditions]. Long-term titrated-dose alpha-glucosidase inhibition in non-insulin-requiring Hispanic NIDDM patients. Long-term efficacy and safety of acarbose in the treatment of obese subjects with non-insulin-dependent diabetes mellitus. Acarbose in NIDDM patients with poor control on conventional oral agents. A 24-week placebo-controlled study. A randomized double-blind trial of acarbose in type 2 diabetes shows improved glycemic control over 3 years (U.K. Prospective Diabetes Study 44) [Non-insulin-dependent diabetes mellitus associated with nonalcoholic liver cirrhosis: an evaluation of treatment with the intestinal alpha-glucosidase inhibitor acarbose]. [The effects of insulin combined with glibenclamide on glucose and lipid metabolism in patients with Type II diabetes mellitus]. Long-term effect of acarbose on glycaemic control in non-insulin-dependent diabetes mellitus: a placebo-controlled double-blind study. The efficacy of acarbose in the treatment of patients with non-insulin-dependent diabetes mellitus. A multicenter controlled clinical trial. Reduction of glycosylated hemoglobin and postprandial hyperglycemia by acarbose in patients with NIDDM. A placebo-controlled dose-comparison study. Clinical experience with acarbose: results of a Canadian multicentre study. Effect on glycemic control of the addition of 2.5 mg glipizide GITS to metformin in patients with T2DM. Chronic treatment of African-American type 2 diabetic patients with alpha-glucosidase inhibition. European study on dose-response relationship of acarbose as a first-line drug in non-insulin-dependent diabetes mellitus: efficacy and safety of low and high doses. A randomized crossover study of sulphonylurea and insulin treatment in patients with type 2 diabetes poorly controlled on dietary therapy. Therapeutic potentials of acarbose as first-line drug in NIDDM insufficiently treated with diet alone. Comparison of acarbose and gliclazide as first-line agents in patients with type 2 diabetes. Glycemic durability of rosiglitazone, metformin, or glyburide monotherapy. Effect of acarbose on insulin sensitivity in elderly patients with diabetes. Beginning insulin treatment of obese patients with evening 70/30 insulin plus glimepiride versus insulin alone. Glimepiride Combination Group. Combined metformin-sulfonylurea treatment of patients with noninsulin-dependent diabetes in fair to poor glycemic control. Efficacy of 6 months monotherapy with glucosidase inhibitor Acarbose versus sulphonylurea glibenclamide on metabolic control of dietary treated type II diabetics (NIDDM). Efficacy and safety of acarbose in metformin-treated patients with type 2 diabetes. Exenatide versus insulin glargine in patients with suboptimally controlled type 2 diabetes: a randomized trial.
The effects of alpha-glucosidase inhibitor (acarbose) were studied in 36 patients with non-insulin-dependent diabetes mellitus (NIDDM), aged 34-67 years with a mean duration of diabetes of 8.8 +/- 0.9 years. They were poorly controlled with diet plus sulfonylurea alone or plus sulfonylurea combined with metformin drugs. Acarbose, 100 mg three times daily, was additionally given to these patients for six months. Results showed small but significant decreases (P < 0.001) in postprandial blood glucose level. Glycosylated hemoglobin level was lowered significantly (P < 0.001) and was normalised (level of < 8%) in 17 per cent of the patients. Fasting serum triglycerides level decreased significantly (P < 0.01), whereas, no significant changes in serum total cholesterol and HDL cholesterol levels were seen. Body weight also decreased significantly (P < 0.001) at the end of acarbose trial. Flatulence was the major side effect of acarbose found in 42 per cent of the patients but it was well-tolerated and may be transient and self-limited. We concluded that the addition of acarbose to the therapeutic regimens of diet therapy plus sulfonylurea or plus sulfonylurea combined with metformin drugs led to significant improvement of glycemic control. Acarbose may be a safe and valuable adjunct to diet and sulfonylurea and metformin treatments in obese, poorly-controlled patients with NIDDM. The treatment of Type II diabetes (NIDDM) includes an appropriate diet and prudent exercise program. If these measures are insufficient to control the blood sugar, oral agents (sulphonylureas or biguanides) or insulin are added to the therapeutic regimen. Although the diet prescription has undergone some changes and refinements, this approach has been the traditional treatment for NIDDM for nearly 40 years. Recently a new class of oral agents, the alpha-glucosidase inhibitors, has become available. These drugs are competitive inhibitors of the alpha-glucosidase enzymes in the brush border of the bowel wall. They act to slow and delay the rate of carbohydrate absorption, thereby decreasing postprandial hyperglycemia. A recent study was designed to evaluate the long-term efficacy of acarbose, an alpha-glucosidase inhibitor, in improving the glycemic control of patients with NIDDM who were sub-optimally controlled on either diet alone, or diet plus sulphonylurea, metformin or insulin. A total of 354 patients with NIDDM were studied, 77 on diet alone, 83 on metformin, 103 and sulphonylurea and 91 on insulin. Subjects in each treatment stratum were randomized, double-blind to either acarbose or placebo, for 1 year. At baseline and every 3 months thereafter, fasting and postprandial glucose and C-peptide, HbA1c and fasting lipids were measured. Compared to placebo, acarbose treatment resulted in a decrease in mean postprandial glucose in all four strata (19 +/- 0.8 to 15.3 +/- 0.7 mmol/l: P < 0.001). This effect was even more pronounced and highly statistically significantly different when comparing the postprandial plasma glucose incremental area under the curve between placebo and acarbose treatment.(ABSTRACT TRUNCATED AT 250 WORDS) The effect of acarbose, an alpha-glucosidase inhibitor, on glycaemic control, was compared with placebo in a double-blind, randomised, group comparison study during 16 weeks in 20 non-obese non-insulin dependent diabetic patients in whom sulphonylurea treatment had been withdrawn. There was significant deterioration in glycaemic control as assessed by HbA1 following withdrawal of the sulphonylurea. There was no significant improvement in HbA1 between weeks 0 and 16 in either the acarbose (11.3% and 12.4% respectively) or the placebo group (10.6% and 12.2% respectively). In both the acarbose and placebo treated groups fasting glucose and insulin concentrations were unaltered. This study also suggests that acarbose was not an effective substitute for sulphonylureas in non-obese Type 2 diabetes uncontrolled by diet alone. The objective of this study was to determine the safety, efficacy, and tolerability of the alpha-glucosidase inhibitor miglitol vs. the sulfonylurea glyburide in the treatment of elderly patients with type 2 diabetes mellitus, inadequately controlled by diet alone. This was a double-blind, randomized, placebo-controlled, 1-yr trial of miglitol 25 mg TID and 50 mg TID compared with placebo and a titrated dose of glyburide in a parallel group comparison study conducted in 30 out-patient sites across the United States. Four hundred eleven (411) diet-treated patients age 60 yr or greater were randomized to receive either placebo TID (n = 101), miglitol 25 mg TID (n = 104), miglitol 50 mg TID (n = 102), or a once-daily dose of glyburide titrated based on fasting plasma glucose (FPG) (n = 104), for a period of 56 weeks. Efficacy was assessed by glycated hemoglobin (HbA1c), fasting and post-meal glucose, insulin, and lipid levels, and by 24-h urinary excretion of glucose and albumin. Safety and tolerability were assessed by tabulation of adverse events, periodic laboratory determinations, and home blood glucose monitoring. HbA1c treatment effects (placebo-subtracted change in HbA1c from baseline) at the 1-yr endpoint were -0.49%, -0.40%, and -0.92% in the miglitol 25 mg TID, miglitol 50 mg TID, and glyburide groups, respectively (P < 0.05- 0.01 vs. placebo). Postprandial insulin levels were significantly greater than placebo and miglitol in the glyburide group (P < 0.01). Hypoglycemia, weight gain, and both routine and serious cardiovascular events were more frequent in the glyburide group (P < 0.05-0.01 vs. placebo or miglitol groups). Diarrhea (or soft stools) and flatulence were more common in both miglitol groups than in the other two groups in a dose-dependent manner, but resulted in relatively few study dropouts. Treatment with miglitol offers the elderly type 2 diabetic patient significant reductions in daylong glycemia as measured by HbA1c. The greater HbA1c reductions seen with once-a-day glyburide occurred at a cost of significant increases in weight, insulin levels, and the incidences of clinical and subclinical hypoglycemia, which did not occur in the miglitol groups. alpha-glucosidase inhibitors are a useful and relatively safe therapeutic option in the elderly patient with type 2 diabetes. Acarbose (Glucobay, Bayer) is a competitive inhibitor of intestinal alpha-glucosidases, which use causes inhibition of carbohydrate digestion. The aim of the study was to prospectively observe scheme of acarbose use as well as efficacy and safety of the drug in diabetic patients in general health care. The study was performed in general health care centres all around Poland. 200 physicians were involved, each one was asked to supervise use of acarbose in 3 patients. The whole patients population consisted of 600 persons. The physicians were asked to make records in provided formularies, prior to acarbose use and then after 4 and 8 weeks of the treatment: data from the interview (among others on diabetes type, disease duration, used diet, treatment incl. sulphonylurea or biguanide derivatives); personal data (age, height, weight, etc.); blood glucose level prior to and 2 hours postprandial; glycosuria; basic additional tests; basic lipid tests (total cholesterol, triglycerides); overall score of acarbose use (side effects, withdrawal, physicians and patients opinion on the drug). Fasting glycaemia was the criterion of inclusion into the analysis. Full data on this parameter were obtained in 480 patients (267 female and 213 male, aged 31-88 years). Acarbose was used as the only antidiabetic drug in 34% of the patients, combined with sulphonylurea in 44%, combined with sulphonylurea and biguanide (metformine) in 19% and combined with metformine only in several cases (3%). During the observation, significant weight and BMI loss, 3% reduction average (for both parameters), was observed in the whole studied group. Fasting and 2 hours postprandial glycaemia was markedly improved in the whole studied population (26.8% and 28.1% glucose level reduction, respectively), and particularly in those who was initially qualified into the group of bad diabetes control (29.4% and 32.4% glucose level decrease, respectively). The most favourable effect on glycaemia was observed for acarbose monotherapy (p < 0.005) when compared to combined treatment). No difference was found in glycaemic response referred to the initial body mass index (BMI). Tested lipid parameters improved during 8-week observation: serum cholesterol level decreased by 4.6% in the whole studied population, and by 8.9% in the group of bad diabetes control, respectively. Value differences did not reach, however, presumed statistical significance (p < 0.005). Significant improvement was noted in triglyceride levels: reductions by 17.5% in the whole group and by as much as 26.8% in the sub-group of bad diabetes control (initial level 200 mg/dl). Acarbose observational study performed in the routine treatment conditions confirmed efficacy of the drug in diabetes mellitus, for both--carbohydrate and lipid metabolism. The study showed low significance of side effects and high acceptation of the treatment by the patients and the physicians. To assess the long-term safety and effectiveness of a titrated dose of the alpha-glucosidase inhibitor miglitol (BAY m 1099) in Hispanic NIDDM patients.
                A 1-year double-blind randomized placebo-controlled study in which diet-treated or diet plus sulfonylurea-treated Hispanic NIDDM patients received either placebo (n = 131) or miglitol in doses of 50, 100, 150, 200 mg t.i.d. (n = 254), up-titrated and down-titrated based on tolerability. Efficacy parameters included changes from baseline in HbA1c, fasting and 2-h postprandial plasma glucose and serum insulin, fasting serum lipids, and urinary albumin-to-creatinine ratio (ACR). Safety assessments consisted primarily of tabulation of adverse events and intercurrent illnesses, and of periodic laboratory determinations.
                Reductions from baseline in HbA1c levels at the 6-month (primary efficacy) endpoint were significantly greater by 0.83% in the miglitol group than in the placebo group. HbA1c reductions in the miglitol treatment group significantly exceeded those in the placebo group by 0.63, 0.73, and 0.92% at 3, 9, and 12 months of treatment, respectively. Reductions in 120-min postprandial glucose and insulin levels were significantly greater in the miglitol group than in the placebo group at all postbaseline visits. There was little difference between treatments for changes in fasting insulin or lipid levels. Miglitol-associated reductions versus placebo in fasting plasma glucose (P = 0.0587 at 6 months) and in ACR (P = 0.0541 at 1-year) were nearly statistically significant. These efficacy results were not notably different between the 6-month endpoint, at which time the mean miglitol dose was 100 mg t.i.d., and the 1-year visit, when the mean miglitol dose was 149 mg t.i.d. Notable adverse events seen significantly more often in the miglitol group than in the placebo group were flatulence and diarrhea (or soft stools). The incidence of these gastrointestinal adverse events appeared to be dose dependent.
                Miglitol treatment of non-insulin-requiring Hispanic NIDDM patients at doses from 50 to 200 mg t.i.d. produced statistically and clinically significant reductions of HbA1c, primarily associated with reduction of glucose and insulin levels in the postprandial period, which were sustained over a year of treatment. Adverse events related to the drug's mechanism of action were common, but generally well tolerated. Doses above 100 mg t.i.d. were not associated with notably enhanced efficacy in most patients. Acarbose delays the release of glucose from complex carbohydrates and disaccharides by inhibiting intestinal alpha-glucosidases, attenuating postprandial increments in blood glucose and insulin. This multicenter double-blind study compared the efficacy and safety of acarbose with placebo in the treatment of obese subjects with non-insulin-dependent diabetes mellitus (NIDDM) managed by diet.
                Two hundred twelve obese subjects with NIDDM who had not received any diabetic medication for at least 12 weeks were randomized to receive acarbose or placebo. The subjects were stratified by fasting glucose level above or below 11.1 mmol/L (200 mg/dL). Based on the subject's therapeutic response and tolerance, the acarbose dosage was titrated from 50 to 300 mg three times per day. This 36-week study consisted of a 6-week pretreatment period, a 24-week double-blind treatment period, and a 6-week posttreatment period.
                Ninety-one subjects given acarbose and 98 subjects who received placebo were evaluable for efficacy. During a standard meal tolerance test at the double-blind end point, the differences between treatment groups in mean change from baseline were as follows: 0.9 mmol/L (16 mg/dL) for fasting plasma glucose level, approximately 2.8 mmol/L (50 mg/dL) for postprandial plasma glucose level, and 0.59% (P < .0001) for hemoglobin A1c concentration (for all three measurements, values decreased in the acarbose group and increased in the placebo group).
                Acarbose improved both fasting and postprandial hyperglycemia and improved overall glycemic control as measured by the hemoglobin A1c level. These findings suggest a beneficial role for acarbose in combination with diet in the treatment of obese subjects with NIDDM. To determine the efficacy of acarbose, compared with placebo, on the metabolic control of NIDDM patients inadequately controlled on maximal doses of conventional oral agents.
                In this three-center double-blind study, 90 Chinese NIDDM patients with persistent poor glycemic control despite maximal doses of sulfonylurea and metformin were randomly assigned to receive additional treatment with acarbose 100 mg thrice daily or placebo for 24 weeks, after 6 weeks of dietary reinforcement. Efficacy was assessed by changes in HbA1c, fasting and 1-h postprandial plasma glucose and insulin levels, and fasting lipid levels.
                Acarbose treatment was associated with significantly greater reductions in HbA1c (-0.5 +/- 0.2% vs. placebo 0.1 +/- 0.2% [means +/- SEM], P = 0.038), 1-h postprandial glucose (-2.3 +/- 0.4 mmol/l vs. placebo 0.7 +/- 0.4 mmol/l, P < 0.001) and body weight (-0.54 +/- 0.32 kg vs. placebo 0.42 +/- 0.29 kg, P < 0.05). There was no significant difference between the two groups regarding changes in fasting plasma glucose and lipids or fasting and postprandial insulin levels. Flatulence was the most common side effect (acarbose vs. placebo: 28/45 vs. 11/44, P < 0.05). One patient on acarbose had asymptomatic elevations in serum transaminases that normalized in 4 weeks after acarbose withdrawal. Another patient on acarbose developed severe hypoglycemia; glycemic control was subsequently maintained on half the baseline dosage of sulfonylurea.
                In NIDDM patients inadequately controlled on conventional oral agents, acarbose in moderate doses resulted in beneficial effects on glycemic control, especially postprandial glycemia, and mean body weight. Additional use of acarbose can be considered as a useful alternative in such patients if they are reluctant to accept insulin therapy. To determine the degree to which alpha-glucosidase inhibitors, with their unique mode of action primarily reducing postprandial hyperglycemia, offer an additional therapeutic approach in the long-term treatment of type 2 diabetes.
                We studied 1,946 patients (63% men) who were previously enrolled in the U.K. Prospective Diabetes Study (UKPDS). The patients were randomized to acarbose (n = 973), titrating to a maximum dose of 100 mg three times per day, or to matching placebo (n = 973). Mean +/- SD age was 59 +/- 9 years, body weight 84 +/- 17 kg, diabetes duration 7.6 +/- 2.9 years, median (interquartile range) HbA1c 7.9% (6.7-9.5), and fasting plasma glucose (FPG) 8.7 mmol/l (6.8-11.1). Fourteen percent of patients were treated with diet alone, 52% with monotherapy, and 34% with combined therapy. Patients were monitored in UKPDS clinics every 4 months for 3 years. The main outcome measures were HbA1c, FPG, body weight, compliance with study medication, incidence of side effects, and frequency of major clinical events.
                At 3 years, a lower proportion of patients were taking acarbose compared with placebo (39 vs. 58%, P < 0.0001), the main reasons for noncompliance being flatulence (30 vs. 12%, P < 0.0001) and diarrhea (16 vs. 8%, P < 0.05). Analysis by intention to treat showed that patients allocated to acarbose, compared with placebo, had 0.2% significantly lower median HbA1c at 3 years (P < 0.001). In patients remaining on their allocated therapy, the HbA1c difference at 3 years (309 acarbose, 470 placebo) was 0.5% lower median HbA1c (8.1 vs. 8.6%, P < 0.0001). Acarbose appeared to be equally efficacious when given in addition to diet alone; in addition to monotherapy with a sulfonylurea, metformin, or insulin; or in combination with more complex treatment regimens. No significant differences were seen in FPG, body weight, incidence of hypoglycemia, or frequency of major clinical events.
                Acarbose significantly improved glycemic control over 3 years in patients with established type 2 diabetes, irrespective of concomitant therapy for diabetes. Careful titration of acarbose is needed in view of the increased noncompliance rate seen secondary to the known side effects. Non-insulin-dependent diabetes mellitus not responding to diet only in patients with non-alcoholic liver cirrhosis is characterized by high post-prandial hyperglycemia. The aim of this study was to evaluate the safety and efficacy of 24 weeks of treatment with 300 mg acarbose per day in 76 consecutive outpatients affected by type 2 diabetes and well-compensated liver cirrhosis. The study design was double-blind cross-over vs placebo. All patients tolerated both treatments well, and no significant variations in liver function tests were observed (< 5% vs pre-treatment). A significant reduction of several parameters was observed only after acarbose: fasting glycemia (19 +/- 6 vs 2 +/- 0.5%; p < 0.01), post-prandial glycemia (41 +/- 9 vs 3 +/- 0.6%; p < 0.01), mean glycemia (30 +/- 8 vs 14 +/- 5%; p < 0.01), daily glycemic variation (52 +/- 8 vs 8 +/- 1%; p < 0.01), HbA1c (16 +/- 1 vs 2 +/- 0.5; p < 0.05), incremental area of C-peptide after a standard meal (80 +/- 19 vs 200 +/- 36 ng/mL/300 min; p < 0.01). After acarbose a significant increase of intestinal voiding/week (98 vs 28%; p < 0.01) and a parallel reduction of blood ammonia levels (52 +/- 9 vs 9 +/- 5%; p < 0.01) were observed. Results clearly document the good tolerability and the absence of toxic effects of acarbose on the liver, due to a theoretic absence of both absorption by the gut and hepatic metabolism of the drug. In fact, acarbose increases peristaltic movement of the gut, stimulates the proliferation of saccharolytic bacteria and simultaneously reduces proteolytic bacterial proliferation, thus actively reducing blood ammonia levels. These unexpected effects of acarbose may be used to advantage for the treatment of type 2 diabetes mellitus in patients with well-compensated liver cirrhosis. We compared the effects of twice-daily insulin injections (n = 22) with combined insulin-glibenclamide therapy (n = 25) on glucose and lipid metabolism in 47 type II diabetic patients (age 69 (SD 9) years, BMI 25.5 (4.8) kg/m2, diabetes duration 9 (range 1-34) years) with secondary failure to sulphonylurea. After 6 months, weight gain averaged 4.2 kg (p less than 0.05), fasting blood glucose had decreased from 14.6 to 8.5 mmol/l (p less than 0.001), HbA1c from 10.9% to 8.1% (p less than 0.001). Twenty-one patients reached HbA1c levels less than 8.0%. Patients on insulin alone injected more insulin (42 vs 26 U daily, p less than 0.01). The decrease of fasting blood glucose and HbA1c was comparable in both groups (p less than 0.001). HDL-cholesterol increased (insulin: 1.10 to 1.24 mmol/l, combined therapy: 1.03 to 1.14 mmol/l, both p less than 0.01), while plasma triglycerides and NEFA decreased (p less than 0.01). Only in patients on insulin alone did total cholesterol decrease from 7.1 to 6.3 mmol/l (p less than 0.001), and LDL-cholesterol from 4.7 to 4.1 mmol/l (p less than 0.05). Apolipoproteins AI, AII and B did not show significant changes. Almost all patients reported improved wellbeing; no severe hypoglycaemias were observed. The efficacy and safety of acarbose therapy (100 mg tds for 24 weeks) was investigated in a placebo-controlled double-blind study in patients with non-insulin dependent diabetes mellitus who could not achieve satisfactory glycaemic control by diet alone. In the acarbose group, the 2 h postprandial blood glucose and haemoglobin A1 levels decreased significantly from 14.0 mmol l-1 to 11.3 mmol l-1 and from 11.1% to 9.7%, respectively. In the placebo group, the 2 h postprandial blood glucose (14.4 mmol l-1 to 14.2 mmol l-1) and the hemoglobin A1 level (10.3% to 9.9%) showed no significant changes. A 75 g oral glucose tolerance test was performed before and after the study, the difference not being significant in either the acarbose group or the placebo group. The incidence of side-effects (mainly gastrointestinal symptoms such as flatulence and abdominal distension) was high at 78.9% in the acarbose group and 61.1% in the placebo group. However, there was no significant difference between the groups, and side-effects in the acarbose group tapered during the trial, suggesting that some at least were not related to the drug. From these findings, it was concluded that acarbose is an effective new treatment for diet treated non-insulin-dependent diabetic patients. To evaluate the long-term efficacy of acarbose, an alpha-glucosidase inhibitor, in improving glycemic control in patients with non-insulin-dependent diabetes mellitus.
                A 1-year, multicenter, randomized, double-blind, placebo-controlled study.
                Seven university-affiliated, community-based, tertiary care diabetes clinics.
                354 patients with non-insulin-dependent diabetes mellitus were recruited; 77 were being treated with diet alone, 83 with diet and metformin, 103 with diet and sulfonylurea, and 91 with diet and insulin. Patients in each treatment group were randomly assigned to either acarbose or placebo for 1 year. Eighty-seven percent of patients receiving acarbose and 92% of those receiving placebo were included in the efficacy analysis (n = 316).
                At baseline and at 3-month intervals, levels of hemoglobin A1c (HbA1c), fasting and postprandial plasma glucose, fasting and postprandial serum C-peptide, and fasting serum lipids were measured.
                Compared with placebo, acarbose treatment caused a significant decrease in the mean postprandial plasma glucose peak (90 minutes) in all four groups (19.0 +/- 0.4 mmol/L to 15.5 +/- 0.4 mmol/L; P < 0.001). Analysis of the postprandial plasma glucose incremental area under the curve showed that the change from baseline to the end of the treatment period differed for placebo and acarbose recipients by 4.73 mmol.h/L in the diet alone group (P < 0.001), 2.06 mmol.h/L in the metformin group (P = 0.01), 2.65 mmol.h/L in the sulfonylurea group (P < 0.001), and 3.13 mmol.h/L in the insulin group (P = 0.001). Corresponding decreases in HbA1c levels occurred; these were 0.9% in the diet alone group (P = 0.005), 0.8% in the metformin group (P = 0.011), 0.9% in the sulfonylurea group (P = 0.002), and 0.4% in the insulin group (P = 0.077). Acarbose did not significantly affect mean serum C-peptide or mean serum lipid levels.
                Acarbose improved long-term glycemic control in patients with non-insulin-dependent diabetes mellitus regardless of concomitant antidiabetic medication. To compare the safety and efficacy of three doses of acarbose (100, 200, and 300 mg three times daily) with placebo for the treatment of non-insulin-dependent diabetes mellitus (NIDDM) in patients maintained on dietary therapy alone.
                This multicenter double-blind placebo-controlled trial was 22 weeks in duration. The trial consisted of a 2-week screening period, a 4-week placebo run-in period, and a 16-week double-blind treatment period. The primary measure of drug efficacy was the mean change from baseline in HbA1c levels. Additional efficacy variables included the mean change from baseline in fasting and postprandial plasma glucose and serum insulin levels.
                After 16 weeks of treatment, acarbose-treated patients had statistically significant reductions in mean HbA1c levels of 0.78, 0.73, and 1.10% (relative to placebo) in the 100-, 200-, and 300-mg t.i.d. groups, respectively. Significant reductions in fasting and postprandial plasma glucose levels, glucose area under the time-concentration curve, and maximum glucose concentration were also observed in acarbose-treated patients. Although there were no statistically significant differences among the 100-, 200-, and 300-mg treatment groups, there was a trend toward a dose-response relationship for most plasma glucose variables that were measured. Gastrointestinal side effects (e.g., abdominal pain, flatulence, and diarrhea) and serum transaminase elevations (e.g., aspartate aminotransferase [AST] and alanine aminotransferase [ALT] were more frequently reported in the acarbose-treated patients than in the placebo-treated control patients. Transaminase elevations occurred only at the 200-, and 300-mg dosages and were readily reversible on discontinuation of treatment.
                Acarbose at doses of 100, 200, and 300 mg administered three times daily for 16 weeks significantly reduced HbA1c levels and postprandial hyperglycemia. Treatment with acarbose is a safe and effective adjunct to dietary therapy for the treatment of NIDDM. Current therapeutic options for the treatment of non-insulin-dependent diabetes mellitus (NIDDM) focus on regimens that primarily lower fasting blood glucose concentrations. In several short-term studies, the alpha-glucosidase inhibitor, acarbose, has been reported to significantly lower post-prandial plasma glucose levels as well as HbA1c. The primary objective of this present study was to assess the long-term efficacy of adjunctive acarbose therapy to improve metabolic control. Over a 1-y period, acarbose or placebo was administered to 4 groups of patients: those managed by diet only, diet and sulfonylurea, diet and biguanide, and diet and insulin. In all treatment groups, the addition of acarbose resulted in significant reductions in postprandial blood glucose levels. Additionally, HbA1C was significantly lower after 12 months of acarbose therapy, compared with placebo, in all groups except the diet and insulin group. The addition of acarbose consequently expands the armamentarium available to clinicians for the optimization of glycemic control in patients with NIDDM. This study evaluated the effects on glycemic control of the addition of 2.5 mg glipizide GITS to metformin in patients with mild-to-moderate, but suboptimally controlled type 2 diabetes.
                In this multicenter, double-blind, placebo-controlled study, 122 patients with type 2 diabetes inadequately controlled (A1c 7-8.5%) on metformin (> or =1000 mg/day for > or =3 months) were randomized to 16 weeks treatment with 2.5 mg/day glipizide GITS (n=61) or placebo (n=61), in addition to their current metformin dose. The primary efficacy variable was the change in A1c from baseline to endpoint. Changes in fasting plasma glucose (FPG), insulin concentrations, lipid profile and safety variables were also measured.
                The addition of glipizide GITS to metformin gave significantly greater improvements in mean A1c and FPG from baseline to endpoint than placebo addition (p<0.0002). Significantly more patients in the glipizide GITS group than in the placebo group achieved the target A1c level of A1c<7.0% (p<0.0001) and an A1c<6.5% (p<0.0033). Fasting insulin concentrations were similar in both groups and unchanged by treatment. Addition of glipizide GITS to metformin did not produce any significant or clinically relevant weight gain or changes in BMI. Both treatment regimens were well tolerated.
                This study showed that the addition of 2.5 mg glipizide GITS to metformin significantly improved glucose control in patients with type 2 diabetes inadequately controlled by metformin monotherapy. To evaluate the long-term efficacy, safety, and tolerability of the alpha-glucosidase inhibitor miglitol in the treatment of African-American patients with type 2 diabetes.
                A total of 345 African-American type 2 diabetic patients (mean age 55.6 years, BMI 31.9 kg/m2, duration of diabetes 4.9 years, baseline HbA1C 8.7%) treated with either diet alone or sulfonylurea were randomized to 1 year of double-blind treatment with either placebo (n = 117) or miglitol (n = 228) at doses of 50 or 100 mg t.i.d., titrated based on tolerability. The primary efficacy criterion was change from baseline in HbA1C at the 6-month visit. Secondarily efficacy parameters included changes from baseline in plasma glucose and serum insulin (both fasting and 120 min after a standardized test meal), fasting lipids, and urinary albumin-to-creatinine ratio. Safety and tolerability evaluations were primarily based on reporting of adverse events and symptoms and on periodic laboratory analyses.
                Miglitol treatment was associated with a mean placebo-subtracted reduction in HbA1C from baseline of 1.19% at 6 months. Fasting and 120-min postprandial plasma glucose levels were reduced in parallel to HbA1C, in association with miglitol treatment. Significant reductions versus placebo in 120-min postprandial insulin levels, in LDL cholesterol, and in fasting triglycerides, were also seen in the miglitol group at individual study time points. Softer, more frequent stools and flatulence were significantly more common in the miglitol group. Urinary tract infections, hematuria, and herpes simplex infections were significantly more common in the placebo group.
                Miglitol treatment appears to be at least as efficacious in the African-American type 2 population as in the U.S. type 2 population at large, with comparable tolerability. alpha-Glucosidase treatment may be an important therapeutic option in these patients in view of their greater risk for microvascular complications and the accumulating body of evidence that better glucose control reduces the risk of these complications. The aim of this double-blind, placebo-controlled, multinational, five-arm study was to investigate the dose-response relationship of acarbose as a first-line drug in the treatment of type 2 diabetes (non-insulin dependent) over a range of minimal and maximal doses according to the European recommendations. The study included 495 patients from 7 countries who were insufficiently controlled with diet alone (glycosylated haemoglobin HbA1C 6.5%-9%). Acarbose, 25, 50, 100 or 200 mg t.i.d., or placebo t.i.d. was given for 24 weeks. Even a low dosage of 25 mg t.i.d. acarbose reduced fasting and postprandial blood glucose levels (1 h postprandial -11.6%; 2 h postprandial -11.3%). Acarbose in a dosage of 200 mg t.i.d. had the greatest effect on these parameters. In the placebo group the mean 2 h postprandial area under the curve (AUC) value for blood glucose was 22.6 mmol/l after 24 weeks' therapy. The mean 2 h postprandial AUC values in the patients given acarbose at doses of 25, 50, 100 and 200 mg t.i.d. were found to be 21.2, 19.6, 20.3 and 18.5 mmol/l, respectively. The corresponding HbA1C values for the placebo and acarbose groups were 7.83%, 7.37%, 7.08%, 6.98% and 6.79%. Interestingly, there was a plateau of blood glucose level at a dosage of 50-100 mg t.i.d. The frequency of flatulence decreased with the duration of drug therapy, but we could not find a linear relationship between doses of acarbose and the gastrointestinal side effects. Less than 3% of patients stopped tablet intake due to adverse events. In 13 non-obese patients with Type 2 diabetes mellitus who failed to achieve adequate blood glucose control on dietary treatment (fasting blood glucose 13.4 +/- 2.7 (+/- SD) mmol l-1, glycosylated haemoglobin 13.0 +/- 1.7%), the effects of 6 months insulin or sulphonylurea therapy on blood glucose control and lipid metabolism were compared in a randomized crossover study. Three patients, who showed a clear improvement on insulin (median glycosylated haemoglobin fell from 14.7 to 8.6%), withdrew from the study prematurely because of subjective and objective signs of hyperglycaemia after crossover from insulin to sulphonylurea. Daily dose after 6 months was 2000 mg tolbutamide (n = 3), 18 +/- 1 mg glibenclamide (n = 7), or 34 +/- 3 U insulin. On insulin, fasting (8.0 +/- 1.9 mmol l-1) and postprandial blood glucose (10.4 +/- 2.7 mmol l-1), and glycosylated haemoglobin (9.5 +/- 1.1%) were lower than on sulphonylurea (11.0 +/- 3.4 mmol l-1, 14.4 +/- 4.8 mmol l-1 and 11.0 +/- 2.5%, respectively, p less than 0.05 in each case). Median increase in body weight was greater on insulin (4.2 vs 1.1 kg, p less than 0.05). Six patients experienced improved well-being on insulin compared with sulphonylurea. Median plasma non-esterified fatty acids decreased from 825 mumol l-1 to 476 mumol l-1 (sulphonylurea) and 642 mumol l-1 (insulin, both p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) Acarbose inhibits alpha-glucosidases of the small intestine and thus delays glucose release from complex carbohydrates. Therefore, its efficacy and acceptability as a first-line drug in non-insulin-dependent diabetes mellitus (NIDDM) insufficiently treated with diet alone was tested in a randomized double-blind placebo-controlled study.
                Ninety-four NIDDM subjects, aged 43-70 yr with average body mass index of 28 kg/m2 and undergoing a pretreatment period of at least 3 mo with diet alone, were treated with 100 mg acarbose three times daily or placebo for 24 wk. The patients were recruited after a 4-wk screening period of dietary reinforcement. The inclusion limits for patients termed diet not satisfactory were fasting blood glucose (FBG) greater than or equal to 7.8 mM and/or postprandial blood glucose (BG) greater than or equal to 10 mM.
                FBG was lowered in the acarbose group from 9.8 to 8.4 mM and in the placebo group from 10.2 to 9.6 mM after 24 wk (P = 0.007 vs. placebo). The most impressive therapeutic effect was a highly significant reduction of postprandial hyperglycemia for at least 5 h after the test meal (1-h postprandial BG with acarbose 10.4 mM and placebo 13.5 mM at 24 wk, P less than 0.001) accompanied by a significant decrease in HbA1 (acarbose 8.65%, placebo 9.32%, P = 0.003). Whereas C-peptide and fasting serum insulin were not significantly affected by acarbose, postprandial insulin increment was approximately 30% lower after 24 wk compared with placebo. Furthermore, acarbose significantly reduced 1-h postprandial triglyceride levels. After an initial phase of greater than 4 wk (when 76.6% in the acarbose group vs. 28% on placebo complained about flatulence, P less than 0.001), the drug was well accepted. At the end of the study, only 32% showed mild or moderate gastrointestinal sensations.
                Extrapolation shows that acarbose is an efficient and acceptable drug for the treatment of NIDDM with poor metabolic control by diet alone. It has beneficial effects on postprandial hyperinsulinemia and postprandial hypertriglyceridemia. To compare the effect of acarbose and gliclazide on clinical findings, biochemical parameters and safety in type 2 diabetic patients insufficiently controlled with medical nutrition therapy (MNT).
                Seventy-two patients (age 35-70 years, BMI < or = 35 kg/m2), who had not taken any oral antidiabetic drug previously, were randomised into two groups after a four-week placebo period, and treated for 24 weeks with acarbose (100 mg two to three times daily) and gliclazide (40-80 mg twice daily). The study was open and 57 patients (33 males and 24 females) completed it. MNT was provided for each patient based on personal requirements as defined by a dietitian. The effect of treatment was evaluated by fasting and postprandial (PP) metabolic parameters (blood glucose, insulin and C peptide levels), HbA1c and plasma lipid levels. In addition, side-effects were recorded and clinical examinations performed.
                Both drugs were effective in reducing of HbA1c, fasting and PP blood glucose levels. However, PP serum insulin levels in the gliclazide group increased more than those in the group treated with acarbose (p = 0.007). Moreover, a small weight reduction was obtained with acarbose treatment but not with gliclazide. Lipid levels were favourably affected by both drugs. Total cholesterol levels decreased in both groups, the decrease only reaching significance in the acarbose group (p = 0.013). However, serum levels of LDL cholesterol decreased in both groups (acarbose and gliclazide, p = 0.033 and p = 0.023, respectively), but the ratio of HDL to LDL cholesterol increased in the acarbose group only (p = 0.045). Both treatments were generally well tolerated. Common complaints in the acarbose group were flatulence and meteorism (29.6%). However, 10.0% of the patients in the gliclazide group reported at least one mild hypoglycaemic episode.
                The results of the study demonstrate that acarbose and gliclazide were reasonably effective in improving metabolic control in patients insufficiently controlled with diet alone, and both treatments were well tolerated. Because of its effects on weight reduction and PP hyperinsulinaemia, acarbose may be preferred as a first-line drug, particularly in the treatment of overweight type 2 diabetic patients. The efficacy of thiazolidinediones, as compared with other oral glucose-lowering medications, in maintaining long-term glycemic control in type 2 diabetes is not known.
                We evaluated rosiglitazone, metformin, and glyburide as initial treatment for recently diagnosed type 2 diabetes in a double-blind, randomized, controlled clinical trial involving 4360 patients. The patients were treated for a median of 4.0 years. The primary outcome was the time to monotherapy failure, which was defined as a confirmed level of fasting plasma glucose of more than 180 mg per deciliter (10.0 mmol per liter), for rosiglitazone, as compared with metformin or glyburide. Prespecified secondary outcomes were levels of fasting plasma glucose and glycated hemoglobin, insulin sensitivity, and beta-cell function.
                Kaplan-Meier analysis showed a cumulative incidence of monotherapy failure at 5 years of 15% with rosiglitazone, 21% with metformin, and 34% with glyburide. This represents a risk reduction of 32% for rosiglitazone, as compared with metformin, and 63%, as compared with glyburide (P<0.001 for both comparisons). The difference in the durability of the treatment effect was greater between rosiglitazone and glyburide than between rosiglitazone and metformin. Glyburide was associated with a lower risk of cardiovascular events (including congestive heart failure) than was rosiglitazone (P<0.05), and the risk associated with metformin was similar to that with rosiglitazone. Rosiglitazone was associated with more weight gain and edema than either metformin or glyburide but with fewer gastrointestinal events than metformin and with less hypoglycemia than glyburide (P<0.001 for all comparisons).
                The potential risks and benefits, the profile of adverse events, and the costs of these three drugs should all be considered to help inform the choice of pharmacotherapy for patients with type 2 diabetes. (ClinicalTrials.gov number, NCT00279045 [ClinicalTrials.gov].).
                Copyright 2006 Massachusetts Medical Society. To study the effect of acarbose, an alpha-glucosidase inhibitor, on insulin release and insulin sensitivity in elderly patients with type 2 diabetes.
                Elderly patients with type 2 diabetes were randomly treated in a double-blind fashion with placebo (n = 23) or acarbose (n = 22) for 12 months. Before and after randomization, subjects underwent a meal tolerance test and a hyperglycemic glucose clamp study designed to measure insulin release and sensitivity.
                After 12 months of therapy there was a significant difference in the change in fasting plasma glucose levels (0.2 +/- 0.3 vs. -0.5 +/- 0.2 mmol/l, placebo vs. acarbose group, respectively; P < 0.05) and in incremental postprandial glucose values (-0.4 +/- 0.6 vs. -3.5 +/- 0.6 mmol/l, placebo vs. acarbose group, P < 0.001) between groups. There was a significant difference in the change in HbA(1c) values in response to treatment (0.4 +/- 0.2 vs. -0.4 +/- 0.1%, placebo vs. acarbose group, P < 0.01). The change in fasting insulin in response to treatment (-2 +/- 2 vs. -13 +/- 4 pmol/l, placebo vs. acarbose group, P < 0.05) and incremental postprandial insulin responses (-89 +/- 26 vs. -271 +/- 59 pmol/l, placebo vs. acarbose group, P < 0.01) was also significantly different between groups. During the hyperglycemic clamps, glucose and insulin values were similar in both groups before and after therapy However, there was a significant difference in the change in insulin sensitivity in response to treatment between the placebo and the acarbose groups (0.001 +/- 0.001 vs. 0.004 +/- 0.001 mg/kg x min(-1) [pmol/l](-1), respectively, P < 0.05)
                Acarbose increases insulin sensitivity but not insulin release in elderly patients with diabetes. This study tested a simple algorithm for beginning insulin for obese patients with type 2 diabetes after sulfonylurea failure, comparing suppertime 70/30 insulin plus continued glimepiride with insulin alone.
                This was a multicenter ambulatory randomized double-masked parallel comparison. There were 208 subjects with secondary failure to sulfonylureas who took glimepiride titrated to 8 mg b.i.d. for 8 weeks; 145 subjects with fasting plasma glucose (FPG) 180-300 mg/dl (10-16.7 mmol/l) on this treatment were randomized to placebo plus insulin (PI) or glimepiride plus insulin (GI) for 24 weeks. A dosage of 70/30 insulin before supper was titrated, seeking fasting capillary blood glucose (FBG) 120 mg/dl (6.7 mmol/l), equivalent to FPG 140 mg/dl (7.8 mmol/l). Outcome measures included FPG, HbA1c, insulin dosage, weight, serum insulin and lipids, and adverse events.
                FPG and HbA1c were equivalent at baseline: 261 vs. 250 mg/dl (14.5 vs. 13.9 mmol/l), and 9.9 vs. 9.7%. At 24 weeks, the FPG target was achieved in both groups (136 vs. 138 mg/dl, 7.6 vs. 7.6 mmol/l), and HbA1c values were equal (7.7 vs. 7.6%). However, with GI, control improved faster and fewer subjects dropped out (3 vs. 15%, P < 0.01), and less insulin was needed (49 vs. 78 U/d, P < 0.001). The outcomes were alike in other respects. No subject had severe hypoglycemia.
                Injection of 70/30 insulin before supper safely restored glycemic control of type 2 diabetes not controlled by glimepiride alone. Control was restored more rapidly and with less injected insulin when glimepiride was continued. The effect of metformin treatment was studied in 13 patients with noninsulin-dependent diabetes mellitus (NIDDM), whose fasting plasma glucose concentration was greater than 10 mmol/L with maximal sulfonylurea doses. Patients were studied before and 3 months after receiving 2.5 g/day metformin. The fasting plasma glucose concentration (12.4 +/- 0.8 vs. 8.8 +/- 0.7 mmol/L), mean hourly postprandial plasma glucose concentration from 0800-1600 h (14.0 +/- 1 vs. 9.4 +/- 0.9 mmol/L), and glycosylated hemoglobin level (12.3 +/- 0.6% vs. 9.0 +/- 0.6%) were all significantly (P less than 0.005-0.001) lower after the administration of metformin. The improvement in glycemic control was associated with a 24% increase (P less than 0.05) in insulin-stimulated glucose uptake during glucose clamp studies and a 16% decrease in basal hepatic glucose production (P less than 0.05). Mean hourly concentrations of plasma insulin (411 +/- 73 vs. 364 +/- 73 pmol/L) and FFA concentrations (440 +/- 31 vs. 390 +/- 40 mumol/L) were also lower after 3 months of metformin treatment. However, neither insulin binding nor insulin internalization by isolated monocytes changed in response to metformin. Finally, plasma triglyceride, very low density lipoprotein triglyceride, and very low density lipoprotein cholesterol were significantly decreased (P less than 0.01-0.001), and high density lipoprotein cholesterol was significantly increased (P less than 0.001) after metformin treatment. Thus, the addition of metformin to sulfonylurea-treated patients with NIDDM not in good glycemic control significantly lowered fasting and postprandial plasma glucose concentrations, presumably due to the combination of enhanced glucose uptake and decreased hepatic glucose production. Since the dyslipidemia present in these patients also improved, the results suggest that metformin may be of significant clinical utility in patients with NIDDM not well controlled with sulfonylurea compounds. Six months monotherapy with Acarbose vs. glibenclamide led to a marked improvement of BG and HbA1 in NIDDM, insufficiently controlled with diet. Beneficial effects of these distinct principles of action were statistically not different. To demonstrate the efficacy, tolerability, and safety of acarbose compared with placebo in patients with type 2 diabetes inadequately controlled with diet and metformin (2,000 or 2,500 mg/day in divided doses).
                This study had a multicenter randomized double-blind placebo-controlled parallel-group comparison design. The trial lasted 31 weeks and consisted of a 1-week screening period, a 6-week placebo pretreatment period, and a 24-week period of acarbose or placebo, with a forced titration from 25-50 mg t.i.d. and a titration of 50-100 mg tid that was based on glucose control. The primary efficacy variable was the mean change from baseline in HbA1c. Secondary efficacy variables included mean changes from baseline in fasting and postprandial plasma glucose, serum insulin, and triglyceride levels.
                The addition of acarbose to patients on background metformin and diet therapy showed a statistically significant reduction in mean HbA1c of 0.65%. There were statistically significant reductions in fasting and postprandial plasma glucose and serum insulin levels compared with placebo. Gastrointestinal side effects were more frequently reported in the acarbose-treated patients. No significant differences in liver transaminase elevations were observed between patients treated with acarbose and those treated with placebo.
                The results of this study demonstrate that the addition of acarbose to patients with type 2 diabetes who are inadequately controlled with metformin and diet is safe and generally well tolerated and that it significantly lowers HbA1c and fasting and postprandial glucose and insulin levels. Physicians may use either insulin or exenatide injections for patients with type 2 diabetes mellitus who have poor glycemic control despite taking oral blood glucose-lowering drugs.
                To compare effects of exenatide and insulin glargine on glycemic control in patients with type 2 diabetes mellitus that is suboptimally controlled with metformin and a sulfonylurea.
                26-week multicenter, open-label, randomized, controlled trial.
                82 outpatient study centers in 13 countries.
                551 patients with type 2 diabetes and inadequate glycemic control (defined as hemoglobin A1c level ranging from 7.0% to 10.0%) despite combination metformin and sulfonylurea therapy.
                Exenatide, 10 microg twice daily, or insulin glargine, 1 daily dose titrated to maintain fasting blood glucose levels of less than 5.6 mmol/L (<100 mg/dL).
                Hemoglobin A1c level, fasting plasma glucose level, body weight, 7-point self-monitored blood glucose, standardized test-meal challenge, safety, and tolerability.
                Baseline mean hemoglobin A1c level was 8.2% for patients receiving exenatide and 8.3% for those receiving insulin glargine. At week 26, both exenatide and insulin glargine reduced hemoglobin A1c levels by 1.11% (difference, 0.017 percentage point [95% CI, -0.123 to 0.157 percentage point]). Exenatide reduced postprandial glucose excursions more than insulin glargine, while insulin glargine reduced fasting glucose concentrations more than exenatide. Body weight decreased 2.3 kg with exenatide and increased 1.8 kg with insulin glargine (difference, -4.1 kg [CI, -4.6 to -3.5 kg]). Rates of symptomatic hypoglycemia were similar, but nocturnal hypoglycemia occurred less frequently with exenatide (0.9 event/patient-year versus 2.4 events/patient-year; difference, -1.6 events/patient-year [CI, -2.3 to -0.9 event/patient year]). Gastrointestinal symptoms were more common in the exenatide group than in the insulin glargine group, including nausea (57.1% vs. 8.6%), vomiting (17.4% vs. 3.7%) and diarrhea (8.5% vs. 3.0%).
                The trial was open-label and did not assess clinical complications related to diabetes. Of the 551 participants, 19.4% of those receiving exenatide and 9.7% of those receiving insulin glargine withdrew from the study. Only 21.6% of the insulin glargine group and 8.6% of the exenatide group achieved the target level for fasting plasma glucose of less than 5.6 mmol/L (<100 mg/dL).
                Exenatide and insulin glargine achieved similar improvements in overall glycemic control in patients with type 2 diabetes that was suboptimally controlled with oral combination therapy. Exenatide was associated with weight reduction and had a higher incidence of gastrointestinal adverse effects than insulin glargine.
It remains unclear whether alpha-glucosidase inhibitors influence mortality or morbidity in patients with type 2 diabetes. Conversely, they have a significant effect on glycemic control and insulin levels, but no statistically significant effect on lipids and body weight. These effects are less sure when alpha-glucosidase inhibitors are used for a longer duration. Acarbose dosages higher than 50 mg TID offer no additional effect on glycated hemoglobin but more adverse effects instead. Compared to sulphonylurea, alpha-glucosidase inhibitors lower fasting and post-load insulin levels and have an inferior profile regarding glycemic control and adverse effects.