Key safety outcomes of SGLT2 inhibitors versus DPP-4 inhibitors in general and vulnerable participants with T2DM: A target trial emulation study.

Authors

Chieh-Li Yen, Pei-Ru Li, Chao-Yi Wu, Chung-Ying Tsai, Jia-Jin Chen, Chang-Chyi Jenq, Hsiang-Hao Hsu, Chang-Fu Kuo, Lai-Chu See, Huang-Yu Yang

Published in

Diabetic medicine : a journal of the British Diabetic Association. Pages e70504. Oct 19, 2026. Epub Oct 19, 2026.

Abstract

Sodium-glucose cotransporter-2 inhibitors (SGLT2i), a class of oral hypoglycaemic agents (OHAs), have demonstrated cardiovascular and renal benefits. However, safety concerns may hinder their broader adoption, particularly among frail populations. We evaluated key safety outcomes associated with SGLT2i compared with dipeptidyl peptidase-4 inhibitors (DPP4i), an OHA class with low risks of complications.
We conducted a target trial emulation (TTE) study using Taiwan's National Health Insurance Research Database (NHIRD) and enrolled participants with type 2 diabetes mellitus (T2DM). Eligible participants were categorized according to newly initiated SGLT2i (n = 224,510) or newly initiated DPP4i (n = 698,012) with continuous use for at least 30 days. Propensity score overlap weighting (PSOW) was used to balance baseline characteristics.
In the intention-to-treat analysis, the SGLT2i group showed significantly lower incidence rate (per person-years) of several safety outcomes than the DPP4i group, including urinary tract infection (UTI) (23.84‰ vs. 27.88‰; hazard ratio [HR], 0.86; 95% confidence interval [CI], 0.84-0.87), fractures or falls (16.55‰ vs. 17.79‰; HR, 0.93; 95% CI, 0.91-0.95), acute kidney injury (AKI) (1.06‰ vs. 1.91‰; HR, 0.55; 95% CI, 0.51-0.59), bullous pemphigoid (0.02‰ vs. 0.07‰; HR, 0.35; 95% CI, 0.23-0.54), and all-cause mortality (13.05‰ vs. 19.72‰; HR, 0.66; 95% CI, 0.65-0.67). Conversely, the risk of genital infection was higher in the SGLT2i group (2.96‰ vs. 2.05‰; HR, 1.44; 95% CI, 1.38-1.51). These findings remained consistent in the per-protocol analysis, across most vulnerable subgroups and individual SGLT2i and DPP4i agents.
SGLT2i, compared with DPP4i, demonstrated a favourable safety profile across most evaluated outcomes, except for genital infections.

PMID:
42896077
Bibliographic data and abstract were imported from PubMed on 20 Oct 2026.

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