Introduction & Objective: The safety profile of the newer diabetes medications in patients with type 2 diabetes (T2D) at low-to-moderate cardiovascular (CV) risk, who represent most people with T2D, remains unexplored. We investigated the association between the use of sodium glucose cotransporter 2 inhibitors (SGLT2i), glucagon-like peptide-1 receptor agonists (GLP1RA), or dipeptidyl peptidase-4 inhibitors (DPP4i) and the risk of several previously reported drug-related harms: diabetic ketoacidosis (DKA), non-vertebral fracture (NVF), lower limb amputation (LLA), urinary tract infection (UTI), and mycotic genital infection (MGI), in this population.
Methods: Using claims data from 2 private health plans and Medicare (2013-2023), we identified pairs of 1:1 propensity score (PS)-matched adults initiating an SGLT2i versus a GLP1RA or a DPP4i. We estimated hazard ratios (HRs) and 95% confidence intervals (CI), adjusting for baseline covariates in the PS model.
Results: Over a mean follow-up of ~11 months, SGLT2i were associated with an over 2-fold increase in risk of DKA and MGI, a slightly higher risk of LLA, a lower risk of UTI, and no difference in NVF risk, vs. GLP1RA or DPP4i (Table).
Conclusion: Compared with GLP1RA or DPP4i, SGLT2i were associated with a higher risk of DKA and MGI, a numerical increase in LLA risk, a lower risk of UTI, and a similar risk of NVF in adults with T2D and low-to-moderate CV risk.
J.M. Paik: None. H. Tesfaye: None. S. Cromer: Other Relationship; Johnson & Johnson Medical Devices Companies. Advisory Panel; Alexion Pharmaceuticals, Inc. Other Relationship; Wolters Kluwer Health. E.O. DiCesare: None. C. Alix: None. D.J. Wexler: Other Relationship; Novo Nordisk. E. Patorno: Research Support; Boehringer-Ingelheim, Food and Drug Administration (FDA), National Institutes of Health, Patient-Centered Outcomes Research Institute.
Patient Centered Outcomes Research Institute (DB-2020C2-20326)
