Improved treatment satisfaction in patients with type 1 diabetes treated with insulin glargine 100U/mL versus neutral protamine Hagedorn insulin: An exploration of key predictors from two randomized controlled trials.

AIM: Investigate contributors to treatment satisfaction in type 1 diabetes (T1D). METHODS: Post-hoc analysis using the Diabetes Treatment Satisfaction Questionnaire status version (DTSQs) in 771 T1D patients from two 28-week trials comparing once-daily insulin glargine 100U/mL (Gla-100) with once- or twice-daily NPH neutral protamine Hagedorn (NPH) insulin. RESULTS: Gla-100 was associated with a significant improvement in treatment satisfaction versus NPH (overall population adjusted mean [standard error] DTSQs change from baseline: +1.13 [0.30] versus -0.04 [0.31]; p=0.006). In the overall population, treatment satisfaction improvement with all insulin regimens was related to less frequent severe hypoglycemia (coefficient-0.077; p=0.040) and HbA1c reduction (-0.066; p=0.082). By treatment regimen, relationships between treatment satisfaction and these outcomes approached or attained statistical significance for NPH insulin, but not Gla-100. In the overall population, predictors of treatment satisfaction improvement included: Gla-100 treatment (estimate 1.17, p=0.006), lower baseline DTSQs (-0.57, p<0.001), study (-1.01, p=0.019), lower severe hypoglycemia rate (0.17, p=0.012), and higher baseline HbA1c (0.44, p=0.014). By treatment regimen, these predictors remained significant for NPH insulin. CONCLUSIONS: Gla-100 resulted in a significant improvement in treatment satisfaction versus NPH insulin, independent of baseline disease characteristics and clinical outcomes.

BeAM value: an indicator of the need to initiate and intensify prandial therapy in patients with type 2 diabetes mellitus receiving basal insulin.

INTRODUCTION: In patients with type 2 diabetes mellitus (T2DM) with uncontrolled glycemia despite ongoing upward titration of basal insulin, targeting postprandial hyperglycemia may be required. Nevertheless, the point at which basal insulin is fully optimized and postprandial glucose (PPG) should be targeted with additional treatment remains unclear. We report here on the BeAM value (difference between bedtime and morning blood glucose values) as an indicator of the need to target PPG. METHODS: This study had 3 stages: exploratory, main, and proof-of-concept analyses. For the exploratory and main analyses, data were pooled from phase 3 trials in adults with T2DM adding basal insulin to oral antidiabetic drugs (OADs). The main analysis included only patients who did not reach A1C ≤7.0% (53 mmol/mol) at week 24. The proof-of-concept analysis used pooled data from phase 3 trials in adults with T2DM adding insulin glargine and a single insulin glulisine injection to OADs. RESULTS: In patients undergoing basal insulin titration, BeAM value increased over 24 weeks (27.8-61.7 mg/dL, n=1188; 32.6-71.2 mg/dL, n=553; exploratory and main analyses, respectively). There were significant correlations between week 24 BeAM value and postprandial contribution to hyperglycemia (Pearson's correlation coefficient (r)=0.375, p<0.001; r=0.396, p<0.001; exploratory and main analyses, respectively). When PPG was targeted (proof-of-concept analysis), the BeAM value reduced from 77.0 to 40.4 mg/dL (n=299). CONCLUSIONS: The BeAM value described in this study is a simple, easy-to-calculate value that may identify patients with T2DM using basal insulin that need targeting of postprandial control rather than advancing basal insulin dose.

Safety and efficacy of insulin glargine 300 u/mL compared with other basal insulin therapies in patients with type 2 diabetes mellitus: a network meta-analysis.

OBJECTIVE: To compare the efficacy and safety of a concentrated formulation of insulin glargine (Gla-300) with other basal insulin therapies in patients with type 2 diabetes mellitus (T2DM). DESIGN: This was a network meta-analysis (NMA) of randomised clinical trials of basal insulin therapy in T2DM identified via a systematic literature review of Cochrane library databases, MEDLINE and MEDLINE In-Process, EMBASE and PsycINFO. OUTCOME MEASURES: Changes in HbA1c (%) and body weight, and rates of nocturnal and documented symptomatic hypoglycaemia were assessed. RESULTS: 41 studies were included; 25 studies comprised the main analysis population: patients on basal insulin-supported oral therapy (BOT). Change in glycated haemoglobin (HbA1c) was comparable between Gla-300 and detemir (difference: -0.08; 95% credible interval (CrI): -0.40 to 0.24), neutral protamine Hagedorn (NPH; 0.01; -0.28 to 0.32), degludec (-0.12; -0.42 to 0.20) and premixed insulin (0.26; -0.04 to 0.58). Change in body weight was comparable between Gla-300 and detemir (0.69; -0.31 to 1.71), NPH (-0.76; -1.75 to 0.21) and degludec (-0.63; -1.63 to 0.35), but significantly lower compared with premixed insulin (-1.83; -2.85 to -0.75). Gla-300 was associated with a significantly lower nocturnal hypoglycaemia rate versus NPH (risk ratio: 0.18; 95% CrI: 0.05 to 0.55) and premixed insulin (0.36; 0.14 to 0.94); no significant differences were noted in Gla-300 versus detemir (0.52; 0.19 to 1.36) and degludec (0.66; 0.28 to 1.50). Differences in documented symptomatic hypoglycaemia rates of Gla-300 versus detemir (0.63; 0.19 to 2.00), NPH (0.66; 0.27 to 1.49) and degludec (0.55; 0.23 to 1.34) were not significant. Extensive sensitivity analyses supported the robustness of these findings. CONCLUSIONS: NMA comparisons are useful in the absence of direct randomised controlled data. This NMA suggests that Gla-300 is also associated with a significantly lower risk of nocturnal hypoglycaemia compared with NPH and premixed insulin, with glycaemic control comparable to available basal insulin comparators.

FASTING VERSUS POSTPRANDIAL HYPERGLYCEMIA AS A TREATMENT TARGET TO LOWER ELEVATED HEMOGLOBIN A1C.

OBJECTIVE: Postprandial hyperglycemia (PPHG) may need addressing when glycemic control cannot be maintained in patients with type 2 diabetes mellitus. We investigated whether glycated hemoglobin A1c (A1c) levels ≥7.0% can indicate postprandial defects warranting prandial therapy after optimized basal insulin therapy. METHODS: From 6 clinical trials of insulin glargine treatment, data were pooled from 496 patients with A1c ≥7.0% after 24 weeks. Patient characteristics and clinical outcomes were summarized according to fasting plasma glucose (FPG) target achievement (<130 mg/dL), postprandial blood glucose (PPBG) levels, and PPBG increments (ΔPPBG). Basal and postprandial contributions to hyperglycemia were determined. RESULTS: After 24 weeks of insulin glargine titration, A1c change from baseline was greater in patients with FPG <130 mg/dL versus ≥130 mg/dL (-1.35% versus -1.11%, respectively; P = .0275), but with increased confirmed hypoglycemia rates (blood glucose <70 mg/dL; 4.06 events/patient-year versus 3.31 events/patient-year; P = .0170). However, increased severe hypoglycemia rates were observed in patients with FPG ≥130 mg/dL. At week 24, postprandial contributions to hyperglycemia increased (>60% regardless of PPBG). Patients with high FPG had lower, but substantial, relative postprandial contributions versus patients achieving FPG target. A similar pattern was observed according to whether patients had a ΔPPBG ≥50 mg/dL after any meal. CONCLUSION: After optimized basal insulin therapy, elevated A1c is the most effective indicator of residual PPHG, regardless of existent FPG or PPBG. When confronted with an uncontrolled A1c after reasonable titration of basal insulin, clinicians should be aware of probable postprandial contributions to hyperglycemia and consider prandial therapy.

Combination therapy with insulin glargine plus metformin but not insulin glargine plus sulfonylurea provides similar glycemic control to triple oral combination therapy in patients with type 2 diabetes uncontrolled with dual oral agent therapy.

AIMS: Evaluate substituting insulin glargine (GLAR) for a thiazolidinedione (TZD) versus adding a third oral antidiabetes drug (OAD) in patients with uncontrolled type 2 diabetes mellitus (T2DM) on TZD+metformin or TZD+sulfonylurea. METHODS: In this multicenter, open-label study, 337 T2DM patients with a glycated hemoglobin A1c (A1C) of 7.5-12.0% despite≥3months of treatment with a TZD plus metformin or a sulfonylurea were randomized to a third OAD (3OAD; metformin or glyburide) or GLAR+1 OAD (metformin or sulfonylurea) with TZD cessation, titrated to a fasting blood glucose≤94mg/dL. RESULTS: Substitution of GLAR for a TZD led to an adjusted mean A1C change from baseline of-1.66% versus-1.86% in the 3OAD arm (adjusted mean difference 0.20 [95% confidence interval, - 0.11, 0.51], not meeting the noninferiority criteria). This difference was driven by the GLAR+sulfonylurea stratum. GLAR+metformin was as effective as 3OAD in achieving glycemic control but with greater improvements in lipid parameters, less weight gain, and lower hypoglycemia rates. CONCLUSIONS: These findings favor substitution of GLAR for a TZD in T2DM patients not controlled on TZD+metformin. GLAR+sulfonylurea was less effective at lowering A1C than 3OAD and not associated with the benefits observed with GLAR+metformin.

Patterns of postprandial hyperglycemia after basal insulin therapy: individual and regional differences.

BACKGROUND: Treatment of postprandial hyperglycemia could be needed when basal insulin added to oral therapy does not maintain glycated haemoglobin (HbA1C ) targets in type 2 diabetes mellitus. Knowing individual and regional patterns of postprandial hyperglycemia in this setting might improve therapeutic decisions. METHODS: Patient-level self-monitored blood glucose data were pooled from six studies of insulin glargine for patients with HbA1C ≥ 7.0% after 24 weeks. Percentages of participants with highest daily postprandial blood glucose and greatest postprandial increments after each of the three daily meals were calculated and compared between four geographical regions; USA, Canada, Germany, and other European countries. RESULTS: For 494 participants (mean age 60.1 years, diabetes duration 9.6 years, and BMI 29.8 kg/m(2) ), mean endpoint HbA1C was 7.8%. On insulin glargine treatment, highest postprandial blood glucose most often occurred post-dinner (44% of participants) and greatest postprandial increments post-breakfast (46% of participants) in all regions. Participants with greatest postprandial increments post-breakfast were older and experienced less HbA1C improvement with insulin glargine than those with greatest postprandial increments after other meals. Post-breakfast and post-dinner postprandial blood glucose was higher in the USA and Canada versus Germany, and in the USA versus Other European countries (all p < 0.05). Postprandial increments after dinner were greater in the USA versus all other regions. CONCLUSIONS: Generally, highest postprandial blood glucose follows dinner and greatest postprandial increments follow breakfast. Variations in patient characteristics and eating patterns might underlie differences both within and between regions. Awareness of regional differences and evaluation of an individual's typical eating pattern might facilitate appropriate prandial therapy.

Weight change in patients with type 2 diabetes starting basal insulin therapy: correlates and impact on outcomes.

BACKGROUND: An increase in body weight is a commonly perceived effect of insulin therapy for type 2 diabetes mellitus, and this may serve as a barrier to insulin initiation and usage. OBJECTIVE: To investigate the baseline clinical and demographic factors associated with weight gain during insulin glargine therapy, and the implications of weight change on clinical outcomes. METHODS: This was a retrospective analysis of patient-level data from phase 3 or 4 randomized controlled, treat-to-target (fasting plasma glucose [FPG] ≤ 100 mg/dL) trials evaluating basal insulin glargine for ≥ 24 weeks. The Pearson correlation coefficient and Cochran-Armitage trend statistic were used to calculate the existence of a trend between absolute and relative weight change, and relative glycated hemoglobin (HbA1c) change from baseline; likelihood of achieving target HbA1c < 7.0%; change from baseline FPG; insulin dose requirements; incidence of hypoglycemia; and adverse events. RESULTS: Eleven studies were included, encompassing a total of 2140 patients. Patients starting insulin glargine treatment gained a mean ± standard deviation 1.8 ± 3.7 kg (4.0 ± 8.2 lb). Most patients had limited weight change (± 2.5 kg or 5.5 lb). Younger age, higher baseline HbA1c, and higher baseline FPG were predictive of greater weight gain (P < 0.0001). Those who gained more weight experienced the largest decrease from baseline in HbA1c and FPG. More weight gain was associated with higher insulin dose requirements, an increased risk of experiencing either symptomatic or glucose-confirmed (< 70 mg/dL) hypoglycemia, and more adverse events. Older patients (> 65 years) were less likely to gain weight or to experience glucose-confirmed hypoglycemia, but more likely to experience severe hypoglycemia. CONCLUSIONS: In this retrospective analysis of patient-level data, most patients had a stable weight (defined as ± 2.5 kg) after 24 weeks of insulin glargine, and weight gain varied with patient demographics. Therefore, insulin glargine can be used in these patient groups with type 2 diabetes without expectation of significant weight gain.

A Patient-level Analysis of Efficacy and Hypoglycaemia Outcomes Across Treat-to-target Trials with Insulin Glargine Added to Oral Antidiabetes Agents in People with Type 2 Diabetes.

Background: A better understanding of hypoglycaemia risk when insulin is used in combination with one or more oral antidiabetes agents may assist in the treatment decision-making process for the clinician and address concerns regarding hypoglycaemia when initiating or intensifying insulin therapy. The objective of this study was to analyse efficacy and hypoglycaemia outcomes in people with type 2 diabetes receiving insulin glargine (IG) with metformin (MET), sulphonylurea (SU) or MET+SU. Methods: Patient-level data were pooled from 15 randomised, treat-to-target trials (fasting plasma glucose [FPG] targets <5.6 mmol/l) with a duration >24 weeks. Efficacy outcomes included glycated haemoglobin (HbA1c), FPG and HbA1c target achievement. Overall hypoglycaemia events were assessed by a confirmed PG value of <3.9, <3.1 and <2.8 mmol/l or assistance required; daytime, nocturnal (00:01-05:59 AM); and severe (assistance required or with confirmed PG <2.0 mmol/l). Results: Overall, 2,837 IG patients were analysed, with either MET (634), SU (906) or MET+SU (1,297) as background oral antidiabetes agents. Endpoint HbA1c in IG+MET and IG+MET+SU-treated patients was significantly lower than in IG+SU-treated patients (adjusted difference -0.32 %; p=0.0001 and -0.33 %; p=0.0002, respectively). Fewer patients achieved endpoint HbA1c <7.0 % with IG+SU (32 %) versus IG+MET (57 %) or IG+MET+SU (49 %). IG+SU and IG+MET+SU led to significant increases in overall, daytime and nocturnal hypoglycaemia versus IG+MET; severe hypoglycaemia was rare. Weight gain was lowest in IG+MET patients (adjusted difference -1.51 kg versus IG+SU; p<0.0001; -0.78 kg versus IG+MET+SU; p=0.0037) despite higher insulin doses (0.51 U/kg versus 0.43 and 0.42 U/kg, respectively). Conclusions: Better glycaemic goal achievement and reduced risk of hypoglycaemia and weight gain were observed with IG+MET versus IG+SU and IG+MET+SU, albeit with an increased insulin dose requirement.

A practice-based research network focused on comparative effectiveness research in type 2 diabetes management.

PURPOSE: To establish a real-world research platform focused on comparative effectiveness research and health care decision making in diabetes care in order to obtain a detailed understanding of individualized patient management in primary care. METHODS: Diabetes FORWARD (Foundation of Real-World Assessment and Research in Diabetes) is a North American research platform being organized to conduct longitudinal, noninterventional investigations of an anticipated 10,000 patients with type 2 diabetes mellitus (T2DM). Recruitment will be stratified to reflect typical (primarily primary care) clinical T2DM populations. Streamlined data collection relying on electronic medical records (retrospective) and periodic surveys (prospective) will reduce the burden of study participation and, therefore, enhance enrollment by busy primary care and endocrinology practices. Physician data will include baseline demographic and practice information. Patient data will include demographics, T2DM characteristics and treatment, resource utilization information, and patient-reported outcomes. Responses can be tracked within the observation window in near-real time, allowing immediate, noninterventional reaction at the point of nonresponse. EXPECTED OUTCOMES: Diabetes FORWARD is expected to provide important real-world data describing how actual clinical T2DM management differs across sites, settings, and clinicians, and its impact on glycemic control, treatment adherence and persistence, and clinical outcomes. These data will also help to identify the effect of diabetes management on the onset and progression of retinopathy, neuropathy, nephropathy, and cardiovascular disease at 6-month intervals. CONCLUSION: To our knowledge, Diabetes FORWARD is the first diabetes-focused, practice-based research network in the United States and Canada. The current study will provide robust data that should reflect typical management of T2DM in clinical practice in North America.

Comparison of safety and efficacy of insulin glargine and neutral protamine hagedorn insulin in older adults with type 2 diabetes mellitus: results from a pooled analysis.

OBJECTIVES: To compare the safety and efficacy of adding insulin glargine or neutral protamine Hagedorn (NPH) insulin to existing oral antidiabetic drug (OAD) regimens in adults with type 2 diabetes mellitus. DESIGN: Pooled analysis of data from five randomized controlled trials with similar designs. SETTING: Three hundred forty-two centers in more than 30 countries worldwide. PARTICIPANTS: Randomly selected individuals aged ≤ 80 with a body mass index ≤ 40 kg/m(2) and a glycosylated hemoglobin (HbA1c) level of 7.5% to 12.0%. MEASUREMENTS: Fixed- and random-effects models were used to compare outcomes after 24 or 28 weeks of treatment (insulin glargine, n = 1,441; NPH insulin, n = 1,254) according to age (≥65, n = 604 vs < 65, n = 2,091) and age based on treatment (e.g., ≥65 receiving insulin glargine vs NPH insulin). Outcomes included change in HbA1c, fasting blood glucose (FBG), insulin dose, and hypoglycemia incidence and event rates. RESULTS: At end point, participants aged 65 and older receiving insulin glargine had greater reductions in HbA1c and FBG than those receiving similar doses of NPH insulin. In contrast, for participants younger than 65, there were no statistically significant differences in reductions in HbA1c or FBG between insulin glargine and NPH insulin. Daytime hypoglycemia rates were similar in all groups, although the rates of nocturnal symptomatic and severe hypoglycemia were lower with insulin glargine than NPH insulin. CONCLUSION: Addition of insulin glargine to oral antidiabetic drugs in older adults with poor glycemic control may have modestly better glycemic benefits than adding NPH insulin, with low risk of hypoglycemia.

A stepwise approach to insulin therapy in patients with type 2 diabetes mellitus and basal insulin treatment failure.

OBJECTIVE: To determine whether 1 or 2 preprandial injections before the meals of greatest glycemic impact can be as effective as 3 preprandial injections in patients with type 2 diabetes mellitus and basal insulin treatment failure. METHODS: This was an open-label, parallel-group, 1:1:1 randomized study of adults with type 2 diabetes mellitus on oral antidiabetic drugs with glycated hemoglobin (A1C) levels of 8.0% or greater. After a 14-week run-in with insulin glargine, patients with an A1C level greater than 7.0% were randomly assigned to 1, 2, or 3 time(s) daily insulin glulisine for 24 weeks. Changes in A1C from randomization to study end; percentage of patients achieving an A1C level less than 7.0%; changes in A1C, fasting glucose concentrations, and weight at individual study points; and safety (adverse events and hypoglycemia) were assessed throughout the study. RESULTS: Three hundred forty-three of 631 patients (54%) completing the run-in phase with insulin glargine were randomly assigned to treatment arms. During the randomization phase, A1C reductions with insulin glulisine once or twice daily were noninferior to insulin glulisine 3 times daily (confidence intervals: -0.39 to 0.36 and -0.30 to 0.43; P>.5 for both). However, more patients met the target A1C with 3 preprandial injections (46 [46%]) than with 2 injections (34 [33%]) or 1 injection (30 [30%]). Severe hypoglycemia occurred in twice as many patients receiving 3 preprandial injections (16%) compared with those receiving 2 injections (8%) and 1 injection (7%), but these differences did not reach significance. CONCLUSION: This study provides evidence that initiation of prandial insulin in a simplified stepwise approach is an effective alternative to the current routine 3 preprandial injection basal-bolus approach.

Validation of the SoloSTAR insulin pen.

BACKGROUND: This study was designed to validate the use of SoloSTAR (sanofi-aventis Deutschland GmbH, Frankfurt, Germany), a new disposable pen developed for use with insulin glargine by patients with type 1 or type 2 diabetes. METHODS: This single-center, open-label, single-arm, sequential trial enrolled subjects with type 1 or type 2 diabetes, 21-78 years old. After face-to-face training (Part 1) or self-training (Part 2), subjects performed three dose-delivery repetitions into an injection pad using separate pens; pens were weighed before and after each dose delivery. The primary outcome was the proportion of subjects delivering successful doses (target dose, 40 units) with all three repetitions. Secondary outcomes included pen accuracy and precision. RESULTS: Validation population included 50 (Part 1) and 54 (Part 2) subjects. In Part 1, 100% of the subjects delivered a successful dose on all three repetitions. In Part 2, 98% of subjects delivered a successful dose on all three repetitions, with five cases of dose-delivery failures reported in the study population. The mean dose delivered was 40.2 units (95% confidence interval [CI], 40.1-40.3 units) in Part 1 and 38.0 units (95% CI, 36.7-39.3 units) in Part 2; 99% and 88% of dose repetitions in Parts 1 and 2, respectively, were within 38-42 units. The safety test was successfully performed by 80% (95% CI, 70.2-88.0%) of subjects in Part 1 and 68% (95% CI, 58.1-77.6%) in Part 2. CONCLUSIONS: This study successfully validated the SoloSTAR pen for use by subjects with or without face-to-face training. SoloSTAR was shown to be easy to use, accurate, and precise.

Adjust to target in type 2 diabetes: comparison of a simple algorithm with carbohydrate counting for adjustment of mealtime insulin glulisine.

OBJECTIVE: Carbohydrate counting is an effective approach to mealtime insulin adjustment in type 1 diabetes but has not been rigorously assessed in type 2 diabetes. We sought to compare an insulin-to-carbohydrate ratio with a simple algorithm for adjusting the dose of prandial insulin glusiline. RESEARCH AND DESIGN METHODS: This 24-week, multicenter, randomized, controlled study compared two algorithms for adjusting mealtime (glulisine) insulin along with a standard algorithm for adjusting background (glargine) insulin in 273 intent-to-treat patients with type 2 diabetes. Glulisine and glargine were adjusted weekly in both groups based on self-monitored blood glucose (SMBG) results from the previous week. The simple algorithm group was provided set doses of glulisine to take before each meal. The carbohydrate counting (carb count) group was provided an insulin-to-carbohydrate ratio to use for each meal and adjusted their glulisine dose based on the amount of carbohydrate consumed. RESULTS: A1C levels at week 24 were 6.70% (simple algorithm) and 6.54% (carb count). The respective mean A1C changes from baseline to 24 weeks were -1.46 and -1.59% (P = 0.24). A1C <7.0% was achieved by 73.2% (simple algorithm) and 69.2% (carb count) (P = 0.70) of subjects; respective values for A1C <6.5% were 44.3 and 49.5% (P = 0.28). The total daily dose of insulin was lower, and there was a trend toward less weight gain in carb count group patients. Severe hypoglycemia rates were low and equal in the two groups. CONCLUSIONS: Weekly basal-bolus insulin adjustments based on premeal and bedtime glucose patterns resulted in significant reductions in A1C. Having two effective approaches to delivering and adjusting rapid-acting mealtime insulin may increase physicians' and patients' willingness to advance therapy to a basal-bolus insulin regimen.

Glimepiride versus metformin as monotherapy in pediatric patients with type 2 diabetes: a randomized, single-blind comparative study.

OBJECTIVE: To compare the efficacy and safety of glimepiride versus metformin in pediatric subjects with type 2 diabetes inadequately controlled with diet and exercise alone or oral monotherapy. RESEARCH DESIGN AND METHODS: This 26-week, single-blind, active-controlled, multinational study randomized 285 subjects to receive glimepiride (1-8 mg once daily) or metformin (500-1000 mg twice daily) for 24 weeks. The primary end point was mean change in A1C from baseline to week 24. Safety was assessed by incidence of hypoglycemia and other adverse events. RESULTS: Significant reductions from baseline A1C were seen in both the glimepiride (-0.54%, P = 0.001) and metformin (-0.71%, P = 0.0002) groups. A total of 42.4% (56 of 132) and 48.1% (63 of 131) of subjects in the glimepiride and metformin groups, respectively, in the intent-to-treat population achieved A1C <7.0% at week 24. No significant differences were observed between groups in reductions in A1C and self-monitored blood glucose levels, changes in serum lipid concentrations, or hypoglycemia incidence. Significant differences were observed in mean changes from baseline in BMI between groups (0.26 kg/m(2) for glimepiride and -0.33 kg/m(2) for metformin; P = 0.003). The adjusted mean body weight increase was 1.97 kg for glimepiride and 0.55 kg for metformin (P = 0.005). A hypoglycemic episode with blood glucose <50 mg/dl (<2.8 mmol/l) was experienced by 4.9 and 4.2% of glimepiride- and metformin-treated subjects, respectively. A single severe hypoglycemic event occurred in each group. CONCLUSIONS: Glimepiride reduced A1C similarly to metformin with greater weight gain, and there was comparable safety over 24 weeks in the treatment of pediatric subjects with type 2 diabetes.

Glimepiride versus pioglitazone combination therapy in subjects with type 2 diabetes inadequately controlled on metformin monotherapy: results of a randomized clinical trial.

OBJECTIVE: To compare the effect of add-on glimepiride or pioglitazone in subjects with type 2 diabetes inadequately controlled on metformin monotherapy. RESEARCH DESIGN AND METHODS: Multicenter, randomized, parallel-group, open-label, forcedtitration study involving 203 adults with poorly controlled type 2 diabetes (A1C 7.5-10%) on metformin monotherapy. Subjects were randomized to receive glimepiride or pioglitazone, titrated to the maximum dose for 26 weeks. Subjects were evaluated for A1C changes, fasting plasma glucose (FPG), insulin, C-peptide, and lipid levels. Safety outcomes and diabetes-related healthcare resource utilization were also evaluated. RESULTS: Both treatment groups achieved similar and significant mean decreases from baseline to endpoint (week 26) in A1C (p = 0.0001) and FPG (p < 0.05). Glimepiride therapy, however, resulted in a more rapid decline in A1C levels at weeks 6, 12, and 20 vs. pioglitazone (p < 0.05). A mean A1C < or = 7% was reached faster in the glimepiride group (median, 80-90 days vs. 140-150 days [p = 0.024]). Total and LDL cholesterol were significantly higher with pioglitazone treatment than with glimepiride at endpoint (p < 0.05). Glimepiride treatment was associated with an increased risk of hypoglycemia and pioglitazone with higher rate of peripheral edema. Healthcare resource utilization was similar between groups, but total healthcare costs were significantly lower for glimepiride versus pioglitazone over the course of the study, driven largely by drug costs. The use of fasting C-peptide concentration > or = 0.27 nmol/L in the inclusion criteria was a potential limitation as it may have included those patients with an improved probability for glimepiride or pioglitazone response. In addition, a larger patient population would have provided a greater degree of data applicability. CONCLUSIONS: In patients with type 2 diabetes inadequately controlled on metformin monotherapy, add-on glimepiride or pioglitazone results in similar overall improvements in glycemic control. Compared with pioglitazone, glimepiride is associated with faster glycemic control, lower total and LDL cholesterol levels and reduced short-term healthcare costs.