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 Diabetes mellitus is an independent risk factor for complications following orthopedic shoulder procedures. Dipeptidyl peptidase-4 (DPP-4) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists are effective agents that manage type 2 diabetes, but their differential effects on perioperative and long-term shoulder outcomes remain unclear.

 We conducted a retrospective cohort study using the TriNetX Research Network, identifying adults (≥18 years) with type 2 diabetes who underwent orthopedic shoulder procedures and were prescribed either a DPP-4 inhibitor or a GLP-1 receptor agonist. Propensity score matching was performed (1:1), adjusting for demographics, comorbidities, and procedure type, yielding 632 patients per cohort. Outcomes included rates of reoperation at one and two years postoperatively and postoperative opioid use.

 At one- and two-year follow-up, rates of reoperation were similar between cohorts. DPP-4 users had significantly higher early postoperative opioid use compared with GLP-1 users (RR: 1.754; 95% CI: 1.440-2.137; p < 0.001), whereas prolonged and chronic postoperative opioid use were similar between cohorts.

 In patients with type 2 diabetes undergoing orthopedic shoulder procedures, DPP-4 inhibitors and GLP-1 receptor agonists demonstrated comparable long-term surgical outcomes, including reoperation rates at one and two years postoperatively. However, early postoperative opioid use was significantly higher among DPP-4 users, while prolonged and chronic opioid utilization were similar between cohorts. These findings support the perioperative safety of both incretin-based therapies and suggest that GLP-1 receptor agonists may confer additional benefit through potential central pain-modulating effects that reduce early postoperative opioid requirements.