A target trial emulation compared adults with type 2 diabetes starting GLP-1 receptor agonists, sulfonylureas, SGLT2 or DPP-4 inhibitors. Records from five University of California centres, 2012 to 2025, gave 70,982 propensity-matched adults followed up to five years. Of 181 outcomes screened, 118 associations met robustness criteria, including false discovery rate control and E-values of at least 1.5. Of these, 65 showed lower risk, including acute myocardial infarction (HR 0.53) and nephritis/nephrosis (HR 0.73). Higher risks included osteoarthritis (HR 1.48), stress fractures (HR 1.68), diverticular disease (HR 1.18 to 1.33) and sleep-wake disorders. The design is observational, so these are associations, drawn from academic medical centres only.
Why it is interesting: The study sets lower cardiovascular and renal risks against higher musculoskeletal and gastrointestinal risks in one population. It compares new users of each drug class with one another, rather than with people taking no diabetes drug.
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