The benefits and risks of DPP4-inhibitors vs. sulfonylureas for patients with type 2 diabetes: accumulated evidence from randomised controlled trial.

AIM: To assess the efficacy and safety of dipeptidyl peptidase 4-inhibitors (DPP4-I) compared with sulphonylureas in adults with type 2 diabetes (T2D) mellitus.

METHOD: Randomised controlled trials were collected from PubMed, EMBASE, Google Scholar and conference. The primary outcome was the change in HbA1c. Secondary outcomes included weight gain, the change in postprandial plasma glucose (PPG), insulin resistance and fasting plasma glucose (FPG), adverse event (AE) and incidence of hypoglycaemia.

RESULTS: Fourteen studies including 5480 patients randomised to DPP4-I and 5214 patients randomised to sulphonylureas were eligible for the meta-analysis. Compared with sulphonylureas, DPP4-I were associated with a smaller decline in HbA1c (WMD, weighted mean differences 0.08%, 95% CI: 0.03-0.14, p = 0.001), and resulted in weight loss of 1.945 kg (95% CI: -2.237 to -1.653, p < 0.0001). The effect of DPP4-I lowering FPG was inferior to that of sulfonylureas (WMD, 0.268 mmol/l, 95% CI, 0.151-0.385, p < 0.0001), and similar in reducing PPG (WMD, 0.084, 95% CI, -0.701 to 0.869, p = 0.833). According to the follow-up period, the included trials were separated into three groups (group 1: less than half one year, group 2: from half one year to 1 year, group 3: more than 1 year). Subgroup analysis showed that the difference in HbA1c between DPP4-I and sulphonylureas presented a decline curve (group 1: 0.50, 95% CI: 0.15-0.84, group 2: 0.05, 95% CI: -0.05 to 0.15, group 3: 0.09, 95% CI: 0.03-0.15). DPP4-I had a favourable insulin resistance compared with sulfonylureas (WMD, -0.673, 95% CI, -1.248 to -0.097, p = 0.022). In addition, compared with sulfonylureas, DPP4-I was associated with a decrease in overall risk for AE (RR, 0.93, 95% CI, 0.91-0.96, p < 0.0001). The incidence of hypoglycaemia was lower with DPP4-I (RR, 0.24, 95% CI, 0.21-0.27, p < 0.001).

CONCLUSION: Patients with T2D who receive DPP4-I could achieve almost similar glycaemic targets with sulphonylureas, with favourable effects on body weight and lower incidence of hypoglycaemia.