A Meta-Analysis of Placebo-Controlled Clinical Trials Assessing the Efficacy and Safety of Incretin-Based Medications in Patients with Type 2 Diabetes

Abstract

Aims: A systematic review of the literature, in combination with a meta-analysis of randomized controlled trials comparing treatments with placebo, was conducted to provide an update on the clinical efficacy and safety of incretin-based medications in adult patients with type 2 diabetes. Methods: A literature search (2000–2009) identified 38 placebo-controlled trials (phase II or later – parallel design) comparing exenatide (n = 8), liraglutide (n = 7), vildagliptin (n = 11) and sitagliptin (n = 12) with placebo. Outcomes were change from baseline in HbA_1c and in weight, and the number of patient-reported hypoglycemic episodes. HbA_1c and weight outcomes were analyzed as weighted mean differences (WMD), and the number of hypoglycemic episodes as relative risks (RR). Results: Patients receiving liraglutide showed greater reduction in HbA_1c in comparison to placebo (WMD = –1.03, 95% confidence interval, CI = –1.16 to –0.90, p < 0.001) than those on sitagliptin (WMD = –0.79, 95% CI = –0.93 to –0.65, p < 0.001), exenatide (WMD = –0.75, 95% CI = –0.83 to –0.67, p < 0.001) or vildagliptin (WMD = –0.67, 95% CI = –0.83 to –0.52, p < 0.001). Weight was statistically significantly negatively associated with exenatide (WMD = –1.10, 95% CI = –1.32 to –0.87, p < 0.001) and positively associated with sitagliptin (WMD = 0.60, 95% CI = 0.33–0.87, p < 0.001) and vildagliptin (WMD = 0.56, 95% CI = 0.27–0.84, p < 0.001). The number of patient-reported hypoglycemic episodes was statistically significantly associated with the use of sitagliptin (RR = 2.56, 95% CI = 1.23–5.33, p = 0.01) and exenatide (RR = 2.40, 95% CI = 1.30–4.11, p = 0.002). Conclusion: Incretin-based therapies are effective in glycemic control and also offer other advantages such as weight loss (exenatide and liraglutide). This may have an important impact on patient adherence to medication.