Sitagliptin compared with the Sulfonylurea Glimepiride provides similar efficacy with less Hypoglycemia and no weight gain when added to ongoing Metformin therapy in patients with Type 2 Diabetes Mellitus (T2DM)

• Published in: Diabetologie und Stoffwechsel
• Main Authors: Seck, T, Williams-Herman, DE, Chen, Y, Duran, L, Johnson-Levonas, AO, Kaufman, KD, Goldstein, BJ
• Format: Conference Proceeding
• Language: English; German
• Published: 21.04.2010
• ISSN: 1861-9002; 1861-9010
• DOI: 10.1055/s-0030-1253887

Question: Current guidelines recommend the addition of another antihyperglycemic agent when glycemic control is not achieved with metformin monotherapy. Sulfonylureas are the most common antihyperglycemic agents used in combination with metformin among patients who do not achieve or maintain glycemic control on metformin alone. In previous studies, the DPP-4 inhibitor sitagliptin (SITA) significantly improved glycemic control and was well tolerated when added to ongoing metformin monotherapy. The current study compared the efficacy and safety of SITA with the commonly-used sulfonylurea glimepiride (GLIM). Methods: A randomized, double-blind study was conducted in patients with T2DM who had inadequate glycemic control (A1C of 6,5%-9,0%) while on a stable dose of metformin (>1500mg/day for >12 weeks). After a 2-week placebo run-in period, 1035 patients were randomized to the addition of SITA 100mg/day (N=516) or GLIM 1mg/day (uptitrated to a potential maximum 6mg/day) (N=519) to ongoing metformin therapy for 30 weeks. The primary analysis evaluated whether SITA was non-inferior to GLIM in reducing A1C from baseline at Week 30. Results: From a mean baseline A1C of 7,49%, LS mean changes at Week 30 were –0,47% for the SITA group and –0,54% for the GLIM group (between-group difference=0,07% [95% CI: –0,03, 0,16]). The upper limit of the 95% CI for the between-group difference in change from baseline in A1C was less than the predefined non-inferiority margin of 0,4%, confirming non-inferiority of SITA versus GLIM. The proportions of patients with A1C <7% at Week 30 were 52,4% (SITA) and 59,6% (GLIM). LS mean changes from baseline in fasting plasma glucose were –14,6mg/dL and –17,5mg/dL for SITA and GLIM, respectively. The proportion of patients for whom the adverse event of hypoglycemia was reported was significantly (p<0,001) lower with SITA (7%; 73 events) than with GLIM (22%; 460 events). Treatment with SITA led to weight loss (–0,8kg) while treatment with GLIM led to weight gain (1,2kg), with a significant (p<0,001) between-group difference of –2,0kg (95% CI: –2,3, –1,6). Conclusions: In this study, the addition of SITA, compared with GLIM, to ongoing metformin therapy in patients with T2DM provided similar A1C-lowering efficacy after 30 weeks. Sitagliptin was generally well tolerated, with a lower risk of hypoglycemia and with weight loss compared with weight gain with glimepiride.