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

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 < 0·0001; I = 83%; 17 studies), cardiovascular events (RR: 0·54; 95% CI, 0·37-0·79; p = 0·002; I = 0%; 6 studies), hypoglycemia (RR: 0·17; 95% CI, 0·13-0·22; p < 0·00001; I = 76%; 17 studies) and severe hypoglycemic events (RR: 0·10; 95% CI, 0·05-0·19; p < 0·00001; I = 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 < 0·00001; I = 0%; 8 studies) and severe hypoglycemic events (RR: 0·26; 95% CI, 0·10-0·66; p = 0·004; I = 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.