Among 224,510 new SGLT2 inhibitor users and 698,012 new DPP-4 inhibitor users with type 2 diabetes in Taiwan's national insurance database, SGLT2i were associated with lower all-cause mortality (HR 0.66), acute kidney injury (HR 0.55), bullous pemphigoid (HR 0.35), urinary tract infection (HR 0.86) and fractures or falls (HR 0.93). Genital infections were the exception, rising 44% (HR 1.44). Results held in per-protocol analysis and most frail subgroups.
The safety signals that make clinicians hesitate, particularly in older or frail patients, largely fail to materialise here. Even UTI risk fell, countering a common fear. The mortality gap is the headline, but it needs cautious reading: this is observational data, and target trial emulation with overlap weighting reduces, but cannot eliminate, confounding. DPP-4 inhibitors are a neutral comparator rather than a placebo, so some of the gap reflects SGLT2i benefit rather than DPP4i harm. The 34% mortality reduction likely overstates what a randomised trial would show, since cardiovascular outcome trials report more modest effects. Residual healthy-user bias is plausible, as sicker patients may be steered toward DPP-4 agents. Findings come from a single East Asian population, so generalisability is uncertain. Editorially, this is confirmatory rather than paradigm-shifting: it reinforces existing cardiorenal evidence and reassures on safety. Patients on SGLT2i should still be counselled on genital hygiene, since mycotic infections remain a real, if manageable, trade-off.