A safety and tolerability profile comparison between dipeptidyl peptidase-4 inhibitors and sulfonylureas in diabetic patients: A systematic review and meta-analysis

Abstract Background The first treatment approach for type 2 diabetes mellitus is lifestyle change and metformin, but it is usually not sufficient. For some time, the anti-hyperglycemic classes of sulfonylureas and dipeptidyl peptidase-4 (DPP-4) inhibitors were considered second-line of treatment, since they show similar efficacy effect. However, the recent ADA-EASD consensus gives the preference to DPP-4 inhibitors compared to sulfonylureas, except if cost is a major problem. We performed a meta-analysis for safety and tolerability profile to comprehend which treatment has less adverse events. Methods PUBMED and EMBASE databases were searched from inception until July 2017 to retrieve RCT studies comparing DPP-4 inhibitors and sulfonylureas treatments in adult type 2 diabetes patients. There was no language restriction. We extracted and combined data from studies comparison that reported safety profile and weight change. A random effect, meta-analytic model was applied to all calculations. Cochrane collaboration tool was used to assess quality and bias of the included studies. Trial registered with PROSPERO (CRD42017075823). Findings Out of 1472 articles identified in our search and screened for eligibility, 36 studies comparing DPP-4 inhibitors and sulfonylureas were identified. DPP-4 inhibitors in combination with metformin had less overall adverse events (RR: 0·90; 95% CI, 0·86–0·94; p  2  = 83%; 17 studies), cardiovascular events (RR: 0·54; 95% CI, 0·37–0·79; p = 0·002; I 2  = 0%; 6 studies), hypoglycemia (RR: 0·17; 95% CI, 0·13–0·22; p  2  = 76%; 17 studies) and severe hypoglycemic events (RR: 0·10; 95% CI, 0·05–0·19; p  2  = 0%; 12 studies). The mean difference of the weight change was 1·92 kg in favor of DPP-4 inhibitors in combination with metformin in relation to sulfonylureas in combination with metformin. Monotherapy with DPP-4 inhibitors also had less rates of hypoglycemia (RR: 0·31; 95% CI, 0·24–0·41; p  2  = 0%; 8 studies) and severe hypoglycemic events (RR: 0·26; 95% CI, 0·10–0·66; p = 0·004; I 2  = 0%; 8 studies) and patients did not gain 1·19 kg. Interpretation These results suggest better safety profile for DPP-4 inhibitors than sulfonylureas for both comparisons, and it is more notable when the treatment regimen includes metformin. Funding This study was funded by Takeda Pharmaceuticals, Brazil.