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Abstract Background: In a previously-published study, adding sitagliptin or glipizide to ongoing metformin therapy provided similar HbA(1c) improvement (both groups, -0.7%) after 52 weeks in patients with type 2 diabetes (T2DM). Significantly fewer patients experienced symptomatic hypoglycemia with sitagliptin (5% of 588 patients) compared to glipizide (32% of 584 patients). Glycemic efficacy and patient characteristics may influence hypoglycemic events. The present analysis evaluated the risk of hypoglycemia with sitagliptin or glipizide after adjusting for the most recently measured HbA(1c) value. Methods: Data for this analysis were from the aforementioned 52-week, randomized, double-blind, active-controlled study. The primary endpoint was confirmed hypoglycemia (i.e., symptomatic hypoglycemia confirmed with a concurrent fingerstick glucose <=70 mg/dL [3.9 mmol/L]); the secondary endpoint was severe hypoglycemia (requiring medical or non-medical assistance or symptoms of neuroglycopenia). Complementary log-log regression random effects models with terms for treatment, most recently measured HbA(1c) value, time (i.e., days since randomization), gender, and age (< or >=65 years) were used to assess adjusted subject-specific treatment effects. Results: Over the full range of HbA(1c) levels and follow-up time, the risk of confirmed hypoglycemic events was lower with sitagliptin compared with glipizide (31 vs. 448 events; adjusted hazard ratio [HR] = 0.05 [95% CI: 0.03, 0.09], p < 0.001). The risk was also lower with sitagliptin in the younger (HR = 0.06 [95% CI: 0.03, 0.12], p < 0.001) and older (HR = 0.02 [0.01, 0.08], p < 0.001) age groups compared with glipizide. For severe hypoglycemia events (2 vs. 22), the risk was lower with sitagliptin (HR = 0.08 [95% CI: 0.01, 0.47]; p = 0.005). Limitations: The actual time between the HbA(1c) measurement and the hypoglycemic event was variable and not controlled for in the analysis. Conclusion: In pre-specified analyses adjusting for the most recently measured HbA(1c) value, there was a substantial reduction in risk for confirmed hypoglycemia with sitagliptin compared to glipizide when added to ongoing metformin therapy in patients with T2DM. The risk of confirmed hypoglycemia was very low in younger and older patients treated with sitagliptin. [ABSTRACT FROM AUTHOR]

Aim: The efficacy and safety of sitagliptin (SITA) monotherapy and SITA/metformin (MET) vs. pioglitazone (PIO) were assessed in patients with type 2 diabetes and moderate-to-severe hyperglycaemia (A1C = 7.5-12.0%). Methods: In an initial 12-week phase (Phase A), 492 patients were randomised 1 : 1 in a double-blind fashion to SITA (100 mg qd) or PIO (15 mg qd, up-titrated to 30 mg after 6 weeks). In Phase B (28 additional weeks), the SITA group was switched to SITA/MET (up-titrated to 50/1000 mg bid over 4 weeks) and the PIO group was up-titrated to 45 mg qd Results: At the end of Phase A, mean changes from baseline were -1.0% and -0.9% for A1C; -26.6 mg/dl and -28.0 mg/dl for fasting plasma glucose; and -52.8 mg/dl and -50.1 mg/dl for 2-h post-meal glucose for SITA and PIO, respectively. At the end of Phase B, improvements in glycaemic parameters were greater with SITA/MET vs. PIO: -1.7% vs. -1.4% for A1C (p = 0.002); -45.8 mg/dl vs. -37.6 mg/dl for fasting plasma glucose (p = 0.03); -90.3 mg/dl vs. -69.1 mg/dl for 2-h postmeal glucose (p = 0.001); and 55.0% vs. 40.5% for patients with A1C < 7% (p = 0.004). A numerically higher incidence of gastrointestinal adverse events and a significantly lower incidence of oedema were observed with SITA/MET vs. PIO. The incidence of hypoglycaemia was similarly low in both groups. Body weight decreased with SITA/MET and increased with PIO (-1.1 kg vs. 3.4 kg; p < 0.001). Conclusion: Improvements in glycaemic control were greater with SITA/MET vs. PIO, with weight loss vs. weight gain. Both treatments were generally well tolerated. [ABSTRACT FROM AUTHOR]

OBJECTIVE: In clinical trials, the degree of glucose lowering with sitagliptin has been correlated with the magnitude of dipeptidyl peptidase-4 (DPP-4) inhibition over 24 h. Previous studies evaluating sitagliptin doses ranging from 25 to 200 mg/day demonstrated that the daily dose of 100 mg provided maximal glucose-lowering efficacy for this compound in patients with type 2 diabetes. However, sitagliptin 200 mg once daily provided numerically greater percent plasma DPP-4 inhibition compared with 100 mg once daily. The purpose of this study was to evaluate whether sitagliptin 200 mg once daily provides greater improvement in glycemic efficacy as assessed by weighted mean glucose (WMG) over 24 h relative to sitagliptin 100 mg once daily and to relate the percent DPP-4 inhibition achieved with these doses to any between-treatment differences in glycemic efficacy. METHODS: In a double-blind crossover study, patients with type 2 diabetes (fasting plasma glucose [FPG] 130-250 mg/dL) were randomized to one of six treatment sequences over three treatment periods (placebo, sitagliptin 100 mg once daily, or sitagliptin 200 mg once daily). Each of the treatment periods was 7 days in duration, with 28-day washout periods between treatments. After each treatment period, patients underwent blood sampling at various time points over 24 h to determine 24-h WMG. Plasma DPP-4 activity was assessed at trough, 24 h following dosing on day 7; percent DPP-4 inhibition was corrected for sample assay dilution. RESULTS: The 103 randomized patients had a baseline mean FPG of 172 mg/dL. Following a planned interim analysis, the study was stopped because the 24-h WMG values were not different between the sitagliptin doses. Furthermore, a significant carryover effect across periods was observed for FPG; thus, efficacy results from period 1 are presented herein. The 24-h WMG values were significantly (p < 0.01) lower with sitagliptin relative to placebo, but the difference between sitagliptin doses was not significant (p = 0.365). Corrected percent plasma DPP-4 inhibition at trough was not significantly (p = 0.791) different with sitagliptin 200 mg (LS mean [95% CI] 96.9% [90.0, 100.0]) compared with sitagliptin 100 mg (95.6% [88.4, 100.0]). The early termination and the carryover effect described above are limitations to this study. CONCLUSION: Across sitagliptin doses in this study, the similarity of the 24-h WMG concentrations and the similarity of the corrected DPP-4 inhibition values support prior findings that the maximal glucose-lowering efficacy of sitagliptin is achieved with once-daily dosing of 100 mg. Clinicaltrials.gov: NCT00541229. [ABSTRACT FROM AUTHOR]

Sitagliptin and glipizide added to metformin provided similar degrees of glycemic efficacy in patients with type 2 diabetes with inadequate glycemic control on metformin monotherapy at 1 year; however, significantly more patients in the sitagliptin group achieved an A1C reduction of >0.5% without hypoglycemia and without an increase in body weight. [ABSTRACT FROM AUTHOR]