Evidence Hub

Comparison of safety profile of DPP4 inhibitors with SGLT2 inhibitors in type 2 diabetes mellitus: systematic review

Z. R. Nimavat, Ankit N. Patel, Alpa Gor, Barna Ganguly

International Journal of Basic & Clinical Pharmacology, 2025

1,903 participants

Abstract

In type 2 diabetes mellitus (T2DM), add-on therapy to metformin is often required. Both sodium-glucose cotransporter-2 (SGLT2) inhibitors and dipeptidyl peptidase-4 (DPP-4) inhibitors are widely used, but differ in their safety profiles due to distinct mechanisms of action. This study aimed to systematically review and compare the safety outcomes of SGLT2 versus DPP-4 inhibitors in patients receiving background metformin therapy. A systematic literature search was conducted in PubMed for studies published from 2006 onward. Randomized controlled trials and observational studies evaluating safety outcomes of SGLT2 inhibitors (empagliflozin, dapagliflozin, canagliflozin) and DPP-4 inhibitors (sitagliptin, teneligliptin, vildagliptin) as add-on to metformin were included. Data on adverse events (AEs), serious adverse events (SAEs), and drug-related adverse events (DRAEs) were extracted and analyzed. Twenty studies met the inclusion criteria: 8 studies on SGLT2 inhibitors (n=946) and 12 on DPP-4 inhibitors (n=1903). The overall incidence of AEs was higher with DPP-4 inhibitors (66%) compared to SGLT2 inhibitors (34%), while DRAEs were comparable (12% vs. 11%). SGLT2 inhibitors were more often associated with genital and urinary tract infections, whereas DPP-4 inhibitors had higher rates of gastrointestinal disturbances and hypoglycemia. Rare events included dehydration and atrial flutter (SGLT2) and dyspepsia and hypertension (DPP-4). Notably, adverse events varied across…

How strong is the evidence?

Evidence Hub reads this as a systematic review, done in people. Its evidence level is 1 of 5 (Highest · pooled evidence). Pooled evidence from several studies sits at the top of the evidence pyramid. Reported size: 1,903 participants or records.

How the five levels of evidence work. The level is assigned automatically from the abstract and can be wrong, so check the paper.

Read the paper

Related studies

Go deeper in Evidence Hub

Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.

Open this study Sign up free