Comparison of bedtime insulin regimens in patients with type 2 diabetes mellitus. A randomized, controlled trial. Comparison of insulin regimens in patients with non-insulin-dependent diabetes mellitus. Efficacy of combined treatments in NIDDM patients with secondary failure to sulphonylureas. Is it predictable? Comparison of combined therapies in treatment of secondary failure to glyburide. Efficacy of conversion from bedtime NPH insulin to morning insulin glargine in type 2 diabetic patients on basal-prandial insulin therapy. Treatment of NIDDM patients with secondary failure to glyburide: comparison of the addition of either metformin or bed-time NPH insulin to glyburide. A randomized controlled trial examining combinations of repaglinide, metformin and NPH insulin. Combination daytime chlorpropamide-metformin/bedtime insulin in the treatment of secondary failures in non insulin dependent diabetes. Intensive replacement of basal insulin in patients with type 1 diabetes given rapid-acting insulin analog at mealtime: a 3-month comparison between administration of NPH insulin four times daily and glargine insulin at dinner or bedtime. Randomized cross-over trial of insulin glargine plus lispro or NPH insulin plus regular human insulin in adolescents with type 1 diabetes on intensive insulin regimens. Efficacy of bedtime NPH insulin with daytime sulfonylurea for subpopulation of type II diabetic subjects. Safety and efficacy of repaglinide in combination with metformin and bedtime NPH insulin as an insulin treatment regimen in type 2 diabetes. Insulin glargine or NPH combined with metformin in type 2 diabetes: the LANMET study. Comparison of bedtime NPH insulin or metformin combined with glibenclamide in secondary sulphonylurea failure in obese type II (NIDDM) patients. Insulin detemir offers improved glycemic control compared with NPH insulin in people with type 1 diabetes: a randomized clinical trial. Efficacy of insulin lispro in combination with NPH human insulin twice per day in patients with insulin-dependent or non-insulin-dependent diabetes mellitus. Multicenter Insulin Lispro Study Group. A randomized multicentre trial of insulin glargine compared with NPH insulin in people with type 1 diabetes. A 26-week, randomized, parallel, treat-to-target trial comparing insulin detemir with NPH insulin as add-on therapy to oral glucose-lowering drugs in insulin-naive people with type 2 diabetes. Repaglinide versus metformin in combination with bedtime NPH insulin in patients with type 2 diabetes established on insulin/metformin combination therapy. A comparison of bedtime insulin glargine with bedtime neutral protamine hagedorn insulin in patients with type 2 diabetes: subgroup analysis of patients taking once-daily insulin in a multicenter, randomized, parallel group study.
Compared with other insulin regimens, combination therapy with oral hypoglycemic agents and bedtime insulin produces similar improvement in glycemic control but induces less weight gain.
                To determine whether bedtime insulin regimens differ with respect to their effects on weight gain in patients with type 2 diabetes.
                Randomized, controlled trial.
                Four outpatient clinics at central hospitals.
                96 patients (mean age, 58 +/- 1 years; mean body mass index, 29 +/- 1 kg/m2) whose type 2 diabetes was poorly controlled with sulfonylurea therapy (mean glycosylated hemoglobin value, 9.9% +/- 0.2%; mean fasting plasma glucose level, 11.9 +/- 0.3 mmol/L [214 +/- 5 mg/dL]).
                Random assignment to 1 year of treatment with bedtime intermediate-acting insulin plus glyburide (10.5 mg) and placebo, metformin (2 g) and placebo, glyburide and metformin, or a second injection of intermediate-acting insulin in the morning. Patients were taught to adjust the bedtime insulin dose on the basis of fasting glucose measurements.
                Body weight, biochemical and symptomatic hypoglycemias, and indices of glycemic control.
                At 1 year, body weight remained unchanged in patients receiving bedtime insulin plus metformin (mean change, 0.9 +/- 1.2 kg; P < 0.001 compared with all other groups) but increased by 3.9 +/- 0.7 kg, 3.6 +/- 1.2 kg, and 4.6 +/- 1.0 kg in patients receiving bedtime insulin plus glyburide, those receiving bedtime insulin plus both oral drugs, and those receiving bedtime and morning insulin, respectively. The greatest decrease in the glycosylated hemoglobin value was observed in the bedtime insulin and metformin group (from 9.7% +/- 0.4% to 7.2% +/- 0.2% [difference, -2.5 +/- 0.4 percentage points] at 1 year; P < 0.001 compared with 0 months and P < 0.05 compared with other groups). This group also had significantly fewer symptomatic and biochemical cases of hypoglycemia (P < 0.05) than the other groups.
                Combination therapy with bedtime insulin plus metformin prevents weight gain. This regimen also seems superior to other bedtime insulin regimens with respect to improvement in glycemic control and frequency of hypoglycemia. Insulin is widely used to improve metabolic control in patients with non-insulin-dependent diabetes mellitus (NIDDM), but there is no consensus about the optimal regimen of insulin treatment.
                We treated 153 patients with NIDDM for three months with five regimens: (1) oral hypoglycemic drug therapy plus NPH insulin given at 7 a.m. (the morning-NPH group), (2) oral hypoglycemic drug therapy plus NPH insulin given at 9 p.m. (the evening-NPH group), (3) NPH and regular insulin (ratio, 70 units to 30 units) given before breakfast and dinner (the two-insulin-injection group), (4) NPH insulin at 9 p.m. and regular insulin before meals (the multiple-insulin-injection group), and (5) continued oral hypoglycemic drug therapy (the control group).
                The mean (+/- SE) value for glycosylated hemoglobin decreased similarly in all four insulin-treatment groups (1.7 +/- 0.3, 1.9 +/- 0.2, 1.8 +/- 0.3, and 1.6 +/- 0.3 percent, respectively). The decrease was significantly greater in these four groups than in the control group (0.5 +/- 0.2 percent; P < 0.001 vs. all insulin-treated groups). Weight gain was significantly less (1.2 +/- 0.5 kg) in the evening-NPH group than in the other insulin-treatment groups (2.2 +/- 0.5 kg in the morning-NPH group, 1.8 +/- 0.5 kg in the two-insulin-injection group, and 2.9 +/- 0.5 kg in the multiple-injection group; P < 0.05). In addition, the increment in the mean diurnal serum free insulin concentration was 50 to 65 percent smaller in the evening-NPH group than in the other insulin-treatment groups. Subjective well-being improved significantly more in the insulin-treatment groups than in the control group (P < 0.001).
                In patients with NIDDM who are receiving oral hypoglycemic drug therapy, the addition of NPH insulin in the evening improves glycemic control in a manner similar to combination therapy with NPH insulin in the morning, a two-insulin-injection regimen, or a multiple-insulin-injection regimen, but induces less weight gain and hyperinsulinemia. The data thus suggest that patients with NIDDM do not benefit from multiple insulin injections and that nocturnal insulin administration appears preferable to daytime administration. The treatment of NIDDM patients with secondary failure to sulphonylurea is a common problem. We performed a crossover study in 50 NIDDM patients with secondary failure to glibenclamide by comparing the addition to sulphonylurea of either a low-dose bedtime NPH insulin or a t.i.d. oral metformin and by analyzing treatment efficacy in relation to patient and disease characteristics. Both combined therapies clearly improved glycaemic control. HbA1 c were similarly reduced by the addition of either bedtime NPH insulin (7.6+/-0.34 vs 8.7+/-0.35, p<0.01) or metformin (7.6+/-0.22 vs 8.6+/-0.31, p<0.01). Also fasting plasma glucose (FPG) and post-prandial plasma glucose (PPPG) significantly decreased (p<0.01) with both treatments. Bed-time NPH insulin was more effective on FPG reduction than metformin (-36+/-2% vs -25+/-2%, p<0.01); in contrast, metformin addition was more effective on PPPG reduction than bedtime NPH insulin addition (-30+/-2% vs 20+/-3%, p<0.01). Serum cholesterol was marginally but significantly decreased after metformin (5.49+/-0.19 vs 5.91 +/-0.18 mM, p<0.05) but not after NPH insulin. Body weight increase was significantly greater after insulin addition than after metformin (1.47+/-0.25 Kg vs 0.64+/-0.17 p=0.02). All patients preferred the addition of metformin rather than NPH insulin. None of the measured clinical and metabolic variables (before treatment FPG and PPPG, HbA1 c, post-glucagon C-peptide levels, insulin sensitivity, patient age, BMI and diabetes duration) significantly correlated to the efficacy of the two combined treatments studied. In conclusion, in NIDDM patients with secondary failure to sulphonylureas the addition of either low-dose bedtime NPH insulin or t.i.d. metformin is similarly effective in improving glycaemic control. Metformin is better accepted by patients and provides a modest advantage in terms of body weight and cholesterol levels. The most common clinical and metabolic variables are not useful for predicting the efficacy of these two combined treatments. To compare the effectiveness of alternative combined treatments in patients with non-insulin-dependent diabetes mellitus (NIDDM) with secondary failure to sulfonylureas.
                A crossover study was carried out by randomly assigning 16 NIDDM patients to a combined treatment with the addition of either a single low-dose bedtime injection of 0.2 U/kg body wt NPH insulin or an oral three times a day administration of 1.5 g/day metformin to the previously ineffective glyburide treatment.
                Both combined therapies significantly (P less than 0.01) reduced fasting plasma glucose (FPG), postprandial plasma glucose (PPPG) and percentage of HbA1. The addition of metformin was more effective than the addition of insulin (P less than 0.01) in improving PPPG in the 8 patients with higher post-glucagon C-peptide levels. In contrast, the efficacy of neither combined therapy was related to patient age, age of diabetes onset, duration of the disease, percentage of ideal body weight, and FPG. The addition of insulin but not metformin caused a significant (P less than 0.01) increase of mean body weight. Neither combined treatment caused changes in serum cholesterol and triglyceride levels. No symptomatic hypoglycemic episode was reported in any of the 16 patients.
                The addition of bedtime NPH insulin or metformin was effective in improving the glycemic control in most NIDDM patients with secondary failure to glyburide. The combination of metformin and sulfonylurea was more effective in reducing PPPG and did not induce any increase of body weight. In normal subjects, approximately half of the daily insulin requirement constitutes basal insulin. We investigated whether increasing the dose of insulin glargine up to half of the total insulin requirement could lead to better glycemic control in type 2 diabetic patients who were treated on basal-prandial insulin therapy. A total of 62 patients with type 2 diabetes on mealtime rapid-acting insulin analogue and bedtime NPH were randomized to either continuation of bedtime NPH (n=31) or morning glargine (n=31) for 6 months while continuing the aspart/lispro at each meal. The two groups were matched for age, sex, diabetes duration, BMI, HbA(1C), endogenous insulin secretion, and proportion of numbers using aspart/lispro and using oral hypoglycemic agents. The dose of insulin glargine was increased by 2-4 units to meet the target fasting blood glucose, whereas the dose of NPH was principally unchanged as a control group. Mean HbA(1C) at baseline was similar between patients with glargine and NPH (7.2% versus 6.9%). The percentage of glargine dose increased significantly (31% at baseline to 48% at 6 months) without any significant changes in total insulin dose. Mean HbA(1C) at 3 months was 6.6% with glargine and 7.0% with NPH (P<0.0001, adjusted mean change between-treatment difference 0.6% [95% CI 0.3-0.9]), and the values at 6 months were 6.6% and 6.9%, respectively (P=0.007). Frequency of hypoglycemia did not differ between the groups. Increasing the dose of glargine without changing the total daily insulin dose resulted in significantly better glycemic control in type 2 diabetic patients on basal-prandial insulin therapy. Conversion from bedtime NPH to morning glargine appears efficacious with no increase in frequency of hypoglycemia. In this study we compared, in 12 NIDDM patients with secondary failure to glyburide, the effect of adding either a single, low-dose bed time NPH insulin injection (0.2 U/Kg) or an oral metformin administration (500 mg x 3) to the previously ineffective sulfonylurea treatment. The addition of both insulin and metformin treatment significantly improved fasting plasma glucose, post-prandial plasma glucose and %HbA1. The effect of both combined therapies was already evident and maximal after 2 weeks of treatment. The addition of bed-time NPH insulin caused a greater decrease of fasting plasma glucose, although the difference with the addition of metformin was not significant. In contrast, the average post-prandial plasma glucose decrease was significantly greater after metformin addition. The addition of bed-time NPH insulin caused a significant increase in average body weight, while after metformin addition, average body weight was unchanged; no change in the average cholesterol and triglyceride level was observed after either combined therapies. To compare combination use of repaglinide, metformin and bedtime Neutral Protamine Hagedorn (NPH) insulin with conventional approaches of insulin initiation in patients with Type 2 diabetes (T2DM).
                Eighty-two patients with T2DM with suboptimal glycaemic control on oral glucose-lowering agents were randomized to one of three treatment regimens for 4 months. Group 1 received metformin and twice daily biphasic 30/70 human insulin mixture (n = 27), group 2 metformin and bedtime NPH insulin (n = 26) and group 3 metformin, bedtime NPH insulin and mealtime repaglinide (n = 25).
                Seventy-five patients completed the study. Baseline and end-point mean HbA1c levels fell from 9.0 +/- 1.1 to 7.9 +/- 1.1% in group 1, 10.0 +/- 2.2 to 9.2 +/- 1.4% group 2 and 10.0 +/- 1.7 to 8.1 +/- 1.5% in group 3, respectively. All groups showed improvements in HbA1c. There was no significant difference between groups in the proportions of patients experiencing hypoglycaemia (29.6, 25.0 and 16.7%, respectively; P = 0.55) or in mean weight gain (2.9, 0.7 and 2.2 kg, respectively; P = 0.06). By 4 months, insulin doses were 0.63 +/- 0.32 IU/kg in group 1, 0.58 +/- 0.21 IU/kg in group 2 and 0.37 +/- 0.22 IU/kg in group 3 (group 3 vs. groups 1 and 2: P < 0.002).
                The approach using repaglinide, metformin and NPH insulin improved glycaemic control with a similar safety profile to conventional insulin initiation in T2DM and produced final glycaemic control similar to metformin and a twice daily biphasic insulin mixture. To determine the effectiveness of the combination therapy with daytime chlorpropamide-metformin and bedtime NPH insulin in the treatment of secondary failures in NIDDM and to study its effects on insulin secretion.
                Non randomized open study with a duration of two months. The patients were followed six months after ending the study. INSTITUTION: Department of Diabetes and Lipid Metabolism. Instituto Nacional de la Nutrición "Salvador Zubirán", Mexico City. CHARACTERISTICS OF THE PATIENTS: Nine patients (seven women and two men) were included. All had NIDDM and secondary failure to antidiabetic oral drugs. Their fasting plasma glucose was 14.5 +/- 2 mM/L and their HbA1c 13.37 +/- 2.9%. At the entry and at the end of the study a 5h-OGTT was done with assays of plasma glucose and C-peptide.
                Chlorpropamide (375 mg/day) plus metformin (1200 mg/day) and bedtime insulin (0.1 U/kg/day).
                After two months on combination therapy, fasting plasma glucose and HbA1c levels were remarkably improved (decreases of 7.3 +/- 0.6 and 9.1 +/- 1.02 respectively, p less than 0.002). The insulin dose was small (6.77 +/- 2.09 U/day). Side effects were minimal and infrequent. During the 5h-OGTT, the mean glucose area under the curve also decreased. The insulin secretion did not change but the C-peptide/glucose ratio increased. At the end of the study, the insulin dose was tapered off and stopped when possible. The four patients with the best glycemic control during the study were able to suspend the bedtime insulin and maintain a good control six months after the insulin suspension.
                The combination therapy is useful in the treatment of secondary failures in NIDDM: Its advantages are the very low mean daily insulin dose needed, the low incidence of side effects and, if a HbA1c less than 8.7% is achieved, the restoration of oral antidiabetic drugs efficacy. The very low insulin dose used in this study could be explained by complementary effects of metformin and bedtime insulin on hepatic glucose output and a putative decrease in peripheral resistance attributable both to sulfonylurea and metformin. To establish differences in blood glucose between different regimens of optimized basal insulin substitution in type 1 diabetic patients given lispro insulin at meals, i.e., NPH injected four times a day versus glargine insulin once daily at dinner or at bedtime.
                A total of 51 patients with type 1 diabetes on intensive therapy (NPH four times/day and lispro insulin at each meal) were randomized to three different regimens of basal insulin substitution while continuing lispro insulin at meals: continuation of NPH four times/day (n = 17), once daily glargine at dinnertime (n = 17), and once daily glargine at bedtime (n = 17) for 3 months. Blood glucose targets were fasting, preprandial, and bedtime concentrations at 6.4-7.2 mmol/l and 2 h after meals at 8.0-9.2 mmol/l. The primary end point was HbA(1c).
                Mean daily blood glucose was lower with dinnertime glargine (7.5 +/- 0.2 mmol/l) or bedtime glargine (7.4 +/- 0.2 mmol/l) versus NPH (8.3 +/- 0.2 mmol/l) (P < 0.05). A greater percentage of blood glucose values were at the target value with glargine at dinner and bedtime versus those with NPH (P < 0.05). HbA(1c) at 3 months did not change with NPH but decreased with glargine at dinnertime (from 6.8 +/- 0.2 to 6.4 +/- 0.1%) and glargine at bedtime (from 7.0 +/- 0.2 to 6.6 +/- 0.1%) (P < 0.04 vs. NPH). Total daily insulin doses were similar with the three treatments, but with glargine there was an increase in basal and a decrease in mealtime insulin requirements (P < 0.05). Frequency of mild hypoglycemia (self-assisted episodes, blood glucose < or =4.0 mmol/l) was lower with glargine (dinnertime 8.1 +/- 0.8 mmol/l, bedtime 7.7 +/- 0.9 mmol/l) than with NPH (12.2 +/- 1.3 mmol/l) (episodes/patient-month, P < 0.04). In-hospital profiles confirmed outpatient blood glucose data and indicated more steady plasma insulin concentrations at night and before meals with glargine versus NPH (P < 0.05). There were no differences between glargine given at dinnertime and at bedtime.
                Regimens of basal insulin with either NPH four times/day or glargine once/day in type 1 diabetic patients both result in good glycemic control. However, the simpler glargine regimen decreases the HbA(1c) level and frequency of hypoglycemia versus NPH. In contrast to NPH, which should be given at bedtime, insulin glargine can be administered at dinnertime without deteriorating blood glucose control. To compare blood glucose control and incidence of nocturnal hypoglycemia in adolescents with type 1 diabetes on multiple injection regimens managed with either an insulin analog combination or NPH insulin plus regular human insulin.
                In a randomized cross-over study, 28 adolescents with type 1 diabetes on multiple injection therapy received either insulin glargine prebedtime plus lispro preprandially (LIS/GLAR) or NPH insulin prebedtime plus regular human insulin preprandially (R/NPH). During each 16-week treatment arm, subjects completed home blood glucose profiles, and at the end of each treatment arm, they were admitted for an overnight metabolic profile. A total of 25 subjects completed the study.
                Compared with R/NPH therapy, LIS/GLAR was associated with lower mean blood glucose levels (LIS/GLAR versus R/NPH): fasting (8.0 vs. 9.2 mmol/l, P < 0.0001), 2 h postbreakfast (8.1 vs. 10.7 mmol/l, P < 0.0005), prelunch (8.9 vs. 10.1 mmol/l, P < 0.01), and 2 h postlunch (8.0 vs. 9.5 mmol/l, P < 0.002). However, there was no difference in mean blood glucose levels before or after the evening meal. Incidence of nocturnal hypoglycemia on overnight profiles was 43% lower on LIS/GLAR compared with R/NPH therapy; however, there was no difference in rates of self-reported symptomatic hypoglycemia. Total insulin dose required to achieve target blood glucose control was lower on LIS/GLAR (1.16 IU/kg) compared with R/NPH therapy (1.26 IU/kg, P < 0.005), but there was no significant difference in HbA(1c) levels (LIS/GLAR versus R/NPH: 8.7 vs. 9.1%, P = 0.13).
                Combination therapy with insulin glargine plus lispro reduced the incidence of nocturnal hypoglycemia and was at least as effective as R/NPH insulin therapy in maintaining glycemic control in adolescents on multiple injection regimens. Although insulin and sulfonylureas often have additive clinical effects when used in combination for type II (non-insulin-dependent) diabetes, these results are variable and a clinical role for this approach is not yet established. This study tests the efficacy of a specific combined regimen for a subpopulation of patients with a randomized double-masked placebo-controlled crossover design and under conditions similar to those of clinical practice. Twenty subjects with limited duration (less than 15 yr) type II diabetes who were moderately obese (less than 160% ideal wt) and proved imperfectly controlled on 10 mg glyburide twice daily completed two 4-mo crossover protocols, comparing a single injection of NPH insulin in the evening plus 10 mg glyburide in the morning with insulin plus placebo. Insulin dose was adjusted by experienced endocrinologists seeking the best glycemic control consistent with safety. All subjects had glycosylated hemoglobin values less than or equal to 150% of the control mean on combined therapy, and combined therapy was superior to insulin alone (fasting plasma glucose 8.0 +/- 0.3 vs. 11.1 +/- 0.6 mM, P less than .01; glycosylated hemoglobin 9.8 +/- 0.1 vs. 10.6 +/- 0.2%, P less than .01). Despite greater weight gain on combined therapy, blood pressure and plasma lipid concentrations were the same on the two regimens. These results suggest this simple regimen offers another option, besides multiple injections of insulin, for patients of this kind who are unsuccessful with a sulfonylurea or a single injection of insulin alone. To evaluate the efficacy and safety of the association of repaglinide, metformin and bedtime NPH insulin compared to two classic regimens: metformin plus NPH and two doses of NPH in patients with poorly controlled type 2 diabetes despite two or more oral antidiabetic drugs (OADs).
                Random, parallel and open study of 24 weeks with 37 patients randomized into three therapeutic groups: group A (n=12) (repaglinide/metformin/NPH), group B (n=12) (metformin/NPH) and group C (n=13) (NPH/NPH). The insulin was adjusted in the visits to obtain a basal blood glucose <110 mg/dl. The endpoint criteria included HbA1c, blood glucose profile, hypoglycemias and body weight.
                At the end of the study, group A presented HbA1c (mean+/-standard deviation) 7.2+/-0.7%, which was significantly less than B (8.8+/-0.1%) and C (8.4+/-1.2%). In terms of absolute reduction, there were only differences (p=0.01) between group A (-2.4+/-1.1%) and B (-0.7+/-1.2%). Group A presented lower postprandial blood glucose values (p<0.01). Nor were there any significant differences in weight gain and incidence of hypoglycemia.
                The combination of repaglinide, metformin and bedtime NPH is safe and effective and it provides better postprandial blood glucose control. The association of metformin and a dose of NPH does not obtain suitable control in patients with a long evolution who have already received two or more OADs. In type 2 diabetic patients we compared 9 months of combination therapy with insulin glargine and metformin with 9 months of NPH insulin combined with metformin. The primary focus was changes in HbA(1c); secondary focus was diurnal glucose profiles and symptomatic hypoglycaemia.
                In this investigator-initiated open, parallel-group clinical trial involving seven centres, 110 insulin-naive type 2 diabetic patients with poor glycaemic control (HbA(1c) >or=8.0%) on oral hypoglycaemic agents (90% using sulfonylurea plus metformin) were randomised to receive bedtime insulin glargine with metformin (G+MET) or bedtime NPH with metformin (NPH+MET) for 36 weeks. The patients were taught how to self-adjust their insulin dose and use a modem to send the results of home glucose monitoring to treatment centres. The goal was to achieve a fasting plasma glucose (FPG) of 4.0 to 5.5 mmol/l in both groups.
                During the last 12 weeks, FPGs averaged 5.75+/-0.02 and 5.96+/-0.03 mmol/l (p<0.001) and insulin doses were 68+/-5 and 70+/-6 IU/day (0.69+/-0.05 and 0.66+/-0.04 IU kg(-1) day(-1), NS) in the G+MET and NPH+MET groups, respectively. At 36 weeks, mean HbA(1c) was 7.14+/-0.12 and 7.16+/-0.14%, respectively (NS). Symptomatic, but not confirmed symptomatic, hypoglycaemia was significantly lower during the first 12 weeks in the G+MET group (4.1+/-0.8 episodes/patient-year) than in the NPH+MET group (9.0+/-2.3 episodes/patient-year, p<0.05), but not significantly different thereafter. Glucose levels before dinner were higher in the NPH+MET group (10.1+/-0.3 mmol/l) than in the G+MET group (8.6+/-0.3 mmol/l, p=0.002) throughout the 36-week study. With regard to baseline characteristics such as initial glycaemia or C-peptide, there was no difference between patients who achieved good glycaemic control (HbA(1c) <7.0%) and those who did not. Differences were seen in the following: between study centres, weight gain during the run-in period and insulin therapy, and FPG during the last 12 weeks (5.7+/-0.2 vs 6.7+/-0.3 mmol/l for patients reaching vs those not reaching target, p<0.01).
                Good glycaemic control can be achieved with both G+MET and NPH+MET. Use of G+MET reduces symptomatic hypoglycaemia during the first 12 weeks and dinner time hyperglycaemia compared with NPH+MET. To compare the effects of bedtime NPH Insulin vs Metformin combined with Glibenclamide in patients who are obese and had secondary failure to sulphonylurea treatment.
                Prospective, randomized, comparative study of patients having type-II diabetes, without complications with associated obesity and secondary failure to sulphonylureas. Thirty-six obese patients who continued to have blood glucose values of fasting > 150 mg/dl and/or random > 220 mg/dl, after 8 weeks of intensive dietary and drug therapy.
                For the 20 weeks of study, the patients were randomised in two equal groups, one receiving 20 to 40 units of NPH Insulin at bed time and the second group, Metformin upto a maximum dose of 3 grams, along with Sulphonylureas.
                Both the groups showed, a significant reduction in the blood glucose values, with an average decrease of 50 mg/dl. The other monitored parameters, such as, serum cholesterol, triglycerides and blood pressure values, also demonstrated a similar downwards trend. However, the drop out rate was high in the Insulin treated group and the remainder group did show slight increase in weight and BMI, while the reverse, stood true, for the metformin group, with 100% compliance rate.
                Metformin, in obese, type II diabetics, with secondary failure to Sulphonylureas, is an effective, safe and well tolerated treatment, which not only improves the metabolic control but also favourably modifies other parameters such as weight, total cholesterol and triglyceride values. Insulin detemir is a soluble long-acting basal insulin analog designed to overcome the limitations of conventional basal insulin formulations. Accordingly, insulin detemir has been compared with NPH insulin with respect to glycemic control (HbA1c, prebreakfast glucose levels and variability, and hypoglycemia) and timing of administration.
                People with type 1 diabetes (n = 408) were randomized in an open-label, parallel-group trial of 16-week treatment duration using either insulin detemir or NPH insulin. Insulin detemir was administered twice daily using two different regimens, either before breakfast and at bedtime (IDet(morn+bed)) or at a 12-h interval (IDet(12h)). NPH insulin was administered before breakfast and at bedtime. Mealtime insulin was given as the rapid-acting insulin analog insulin aspart.
                With both insulin detemir groups, clinic fasting plasma glucose was lower than with NPH insulin (IDet(12h) vs. NPH, -1.5 mmol/l [95% CI -2.51 to -0.48], P = 0.004; IDet(morn+bed) vs. NPH, -2.3 mmol/l (-3.32 to -1.29), P < 0.001), as was self-measured prebreakfast plasma glucose (P = 0.006 and P = 0.004, respectively). The risk of minor hypoglycemia was lower in both insulin detemir groups (25%, P = 0.046; 32%, P = 0.002; respectively) compared with NPH insulin in the last 12 weeks of treatment, this being mainly attributable to a 53% reduction in nocturnal hypoglycemia in the IDet(morn+bed) group (P < 0.001). Although HbA1c for each insulin detemir group was not different from the NPH group, HbA1c for the pooled insulin detemir groups was significantly lower than for the NPH group (mean difference -0.18% [-0.34 to -0.02], P = 0.027). Within-person between-day variation in self-measured prebreakfast plasma glucose was lower for both detemir groups (both P < 0.001). The NPH group gained weight during the study, but there was no change in weight in either of the insulin detemir groups (IDet(12h) vs. NPH, -0.8 kg [-1.44 to -0.24], P = 0.006; IDet(morn+bed) vs. NPH, -0.6 kg [-1.23 to -0.03], P = 0.040).
                Overall glycemic control with insulin detemir was improved compared with NPH insulin. The data provide a basis for tailoring the timing of administration of insulin detemir to the individual person's needs. A common treatment regimen for patients with either insulin-dependent diabetes mellitus (IDDM) or non-insulin-dependent diabetes mellitus (NIDDM) is a combination of rapid-acting insulin and intermediate-acting insulin administered twice each day. It is usually recommended that regular human insulin be injected 30 to 45 minutes before a meal. In practice, patients often inject regular human insulin closer to mealtime, causing a higher post-prandial serum glucose level and an increased potential for hypoglycemia in the postabsorptive period. Insulin lispro, a rapid-acting insulin analogue, is best injected just before a meal because of its more rapid absorption and shorter duration of action. In 707 randomized patients, 379 with IDDM and 328 with NIDDM, we studied the effect of twice-daily insulin lispro or regular human insulin in combination with NPH human insulin (isophane insulin) on premeal, 2-hour postprandial, and bedtime glycemic control. Assessments were based on the results of a seven-point blood glucose profile, the insulin dose (by formulation and time of administration), the incidence and frequency of hypoglycemic episodes, and the glycated hemoglobin value. Treatment with insulin lispro resulted in lower postprandial glucose levels and smaller increases in glucose level after the morning and evening meals compared with treatment with regular human insulin. Overall glycemic control, frequency of hypoglycemic events, and total insulin dose were not different between the two groups. Insulin lispro in combination with NPH human insulin in a twice-per-day regimen allows injection closer to mealtime and improves post-prandial glycemic control without increasing the risk of hypoglycemia. To compare insulin glargine with NPH human insulin for basal insulin supply in adults with type 1 diabetes.
                People with type 1 diabetes (n = 585), aged 17-77 years, were randomized to insulin glargine once daily at bedtime or NPH insulin either once- (at bedtime) or twice-daily (in the morning and at bedtime) according to their prior treatment regimen and followed for 28 weeks in an open-label, multicentre study. Both groups continued with pre-meal unmodified human insulin.
                There was no significant difference between the two insulins in change in glycated haemoglobin from baseline to endpoint (insulin glargine 0.21 +/- 0.05% (mean +/- standard error), NPH insulin 0.10 +/- 0.05%). At endpoint, self-monitored fasting blood glucose (FBG) had decreased similarly in each group (insulin glargine -1.17 +/- 0.12 mmol/L, NPH insulin -0.89 +/- 0.12 mmol/L; p = 0.07). However, people on >1 basal insulin injection per day prior to the study had a clinically relevant decrease in FBG on insulin glargine versus NPH insulin (insulin glargine -1.38 +/- 0.15 mmol/L, NPH insulin -0.72 +/- 0.15 mmol/L; p < 0.01). No significant differences in the number of people reporting >or=1 hypoglycaemic episode were found between the two groups, including severe and nocturnal hypoglycaemia. Insulin glargine was well tolerated, with a similar rate of local injection and systemic adverse events versus NPH insulin.
                A single, bedtime, subcutaneous dose of insulin glargine provided a level of glycaemic control at least as effective as NPH insulin, without an increased risk of hypoglycaemia.
                Copyright (c) 2005 John Wiley & Sons, Ltd. To assess efficacy and tolerability of insulin detemir or NPH insulin added to oral therapy for type 2 diabetes in a treat-to-target titration protocol.
                Individuals (n = 476) with HbA(1c) (A1C) 7.5-10.0% were randomized to addition of twice-daily insulin detemir or NPH insulin in a parallel-group, multicenter trial. Over 24 weeks, insulin doses were titrated toward prebreakfast and predinner plasma glucose targets of < or =6.0 mmol/l (< or =108 mg/dl). Outcomes assessed included A1C, percentage achieving A1C < or =7.0%, risk of hypoglycemia, and body weight.
                At 24 weeks, A1C had decreased by 1.8 and 1.9% (from 8.6 to 6.8 and from 8.5 to 6.6%) for detemir and NPH, respectively (NS). In both groups, 70% of participants achieved an A1C </= 7.0%; [corrected] there was a trend towards [corrected] the proportion achieving this without hypoglycemia being [corrected] higher with insulin detemir than with NPH insulin (34% [corrected] vs. 25[corrected]%, P = 0.052[corrected]). Compared with NPH insulin, the risk for all hypoglycemia with insulin detemir was reduced by 47% (P < 0.001) and nocturnal hypoglycemia by 55% (P < 0.001). Mean weight gain was 1.2 kg with insulin detemir and 2.8 kg with NPH insulin (P < 0.001), and the difference in baseline-adjusted final weight was -1.58 (P < 0.001).
                Addition of basal insulin to oral drug therapy in people with suboptimal control of type 2 diabetes achieves guideline-recommended A1C values in most people with aggressive titration. Insulin detemir compared with NPH insulin achieves this with reduced hypoglycemia and less weight gain. To compare the effect on glycemic control and weight gain of repaglinide versus metformin combined with bedtime NPH insulin in patients with type 2 diabetes.
                A total of 80 subjects treated with 850 or 1,000 mg t.i.d. metformin combined with bedtime NPH insulin were randomized to 13 weeks of open-label treatment with 4 mg t.i.d. repaglinide (n = 39) or metformin (dose unchanged) (n = 41). Insulin dose was titrated at the clinician's discretion, aiming for a fasting blood glucose (FBG) < or =6.0 mmol/l.
                Baseline age, diabetes duration, insulin requirement, weight, BMI, FBG, and HbA(1c) (Diabetes Control and Complications Trial-aligned assay, normal range 4.6-6.2%) were similar. Glycemic control improved (nonsignificantly) with insulin/metformin by (mean) 0.4%, from 8.4 to 8.1% (P = 0.09) but deteriorated with insulin/repaglinide by (mean) 0.4%, from 8.1 to 8.6% (P = 0.03; P = 0.005 between groups). Weight gain was less with insulin/metformin: 0.9 +/- 0.4 kg (means +/- SE) (P = 0.01) versus 2.7 +/- 0.4 kg (P < 0.0001) (P = 0.002 between groups). The Diabetes Treatment Satisfaction Questionnaire score (potential range 0 [minimum] to 36 [maximum]) increased from 32.4 +/- 0.8 to 34.1 +/- 0.5 (P = 0.01) with insulin/metformin but decreased from 32.5 +/- 0.9 to 29.1 +/- 1.3 (P < 0.002) with insulin/repaglinide.
                Combined with bedtime NPH insulin, metformin provides superior glycemic control to repaglinide with less weight gain and improved diabetes treatment satisfaction. Basal insulin is frequently administered once daily. This subgroup analysis of a multicenter, randomized, parallel study compared insulin glargine (Lantus Aventis Pharmaceuticals, Bridgewater, NJ) with neutral protamine Hagedorn (NPH) insulin in patients with type 2 diabetes, evaluating only patients treated previously with once-daily NPH insulin.
                Patients received bedtime insulin glargine or NPH insulin, with preprandial regular insulin. One hundred patients (mean age, 57.9 years; mean glycohemoglobin, 8.4%; mean fasting blood glucose, 167 mg/dL) were treated for up to 28 weeks.
                Patients treated with insulin glargine (n = 52) and NPH insulin (n = 48) achieved similar reductions from baseline in glycohemoglobin (-0.41% versus -0.46%) and fasting blood glucose (-22 mg/dL versus -22 mg/dL) at week 28. The proportion of patients reaching target fasting blood glucose (<120 mg/dL) at 28 weeks was 34.2% with insulin glargine and 24.4% with NPH insulin. Similar proportions of patients achieved glycohemoglobin less than 7% and less than 8% in both groups. Baseline and week-28 mean daily doses of insulin glargine (27.3 IU versus 36.4 IU) were similar to NPH insulin doses (25.5 IU versus 30.2 IU). However, significantly fewer patients reported one or more episodes of hypoglycemia with insulin glargine (46.2%) versus NPH insulin (60.4%; P < 0.05). Significantly fewer patients also reported one or more symptomatic episodes confirmed by blood glucose less than 50 mg/dL with insulin glargine (17.3%) versus NPH insulin (31.3%; P < 0.005).
                Bedtime insulin glargine is as effective as bedtime NPH insulin in improving glycemic control, with significantly less hypoglycemia.
Bedtime NPH insulin combined with oral hypoglycaemic agents provides comparable glycaemic control to insulin monotherapy and is associated with less weight gain if metformin is used.