Eureka! Institutional Repository

Introduction/Objective: Omarigliptin and trelagliptin are two novel DPP-4 inhibitors administered once weekly. A systematic review and meta-analysis was performed in order to assess the efficacy and safety of once-weekly DPP-4 inhibitors (DPP-4i qw) in adults with type 2 diabetes mellitus (T2DM). Methods: Medline, Embase, the Cochrane Library and grey literature sources were searched for randomized controlled trials comparing DPP-4i qw with placebo or other antidiabetic agents through February 2016. Primary outcome was change in HbA1c. Secondary outcomes included change in body weight, incidence of hypoglycaemia and other adverse events. Results: 13 primaries studies with 5177 participants, including 9 studies with omarigliptin and 4 studies with trelagliptin, were used for the meta-analysis. We also identified 4 additional completed trials with undisclosed results and 2 ongoing trials. Compared to placebo, DPP-4i qw were superior in HbA1c reduction either as monotherapy or as add-on treatment (WMD –0.73%; 95% CI –0.87 to –0.60; I2 = 73%). Compared with active comparators, DPP-4i qw were equally effective in HbA1c lowering (WMD 0.09%; 95% CI –0.03 to 0.21%; I2 = 66%). Omarigliptin compared to placebo was neutral in body weight change (WMD 0.60 kg; 95% Cl 0.25 to 0.96; I2 = 0%). Incidence of any hypoglycaemia did not differ between DPP4i qw and placebo (OR 1.32; 95% CI 0.78 to 2.22; I2 = 0%) but was lower compared to active comparators (OR 0.27; Cl 0.18 to 0.38; I2 = 74%). Incidence of severe hypoglyaemia was similar between DPP-4i qw and placebo or active comparators. The incidence of all the other analyzed adverse events, including a post-hoc analysis for coronary artery events, prostate cancer and hepatobiliary disorders did not differ from that observed with any comparators. Conclusion: Given the convenient dosing scheme and overall efficacy and safety profile, DPP-4i qw may represent an alternative therapeutic option for T2DM, especially where medication adherence is a concern. However, their long-term effect on hard clinical outcomes and comparative effectiveness against injectable therapies remain to be clarified.