Key safety outcomes of
SGLT2
inhibitors versus
DPP
‐4 inhibitors in general and vulnerable participants with
T2DM
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 Abstract
Aims
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.
Methods
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.
Results
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.
Conclusions
SGLT2i, compared with DPP4i, demonstrated a favourable safety profile across most evaluated outcomes, except for genital infections.