ArticleCureus2026
Dipeptidyl Peptidase-4 (DPP-4) Inhibitors Are Associated With Reduced Early but Increased Chronic Postoperative Opioid Use After Shoulder Surgery.
Article in Cureus, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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7 authors.
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Abstract
Background Diabetes mellitus increases the risk of postoperative complications following orthopedic shoulder surgery. Dipeptidyl peptidase-4 (DPP-4) inhibitors are widely prescribed for glycemic control in type 2 diabetes mellitus, yet their influence on perioperative and long-term postoperative outcomes remains unclear. Methods A retrospective cohort study was conducted using the TriNetX Research Network to identify adults (≥18 years) with type 2 diabetes who underwent orthopedic shoulder procedures and were either prescribed or not prescribed a DPP-4 inhibitor. After 1:1 propensity score matching for demographics, comorbidities, and procedure type, 834 patients were included in each cohort. Outcomes included 30-day emergency department (ED) visits, one- and two-year reoperation rates, and postoperative opioid use. Results ED visits and reoperation rates at one and two years were similar between cohorts. DPP-4 inhibitor users demonstrated significantly lower rates of early postoperative opioid use compared with non-users (33.6% vs. 45.3%; RR: 0.741; 95% CI: 0.656-0.836; p < 0.001). No significant difference was observed in prolonged opioid use (21.5% vs. 21.2%; RR: 1.011; 95% CI: 0.841-1.216; p = 0.952). However, DPP-4 users had significantly higher rates of chronic postoperative opioid use (21.2% vs. 13.7%; RR: 1.553; 95% CI: 1.252-1.925; p < 0.001). Conclusion DPP-4 inhibitor exposure within six months prior to shoulder surgery was not associated with differences in long-term surgical outcomes or early emergency medical utilization among patients with type 2 diabetes. However, DPP-4 users demonstrated lower early but higher chronic postoperative opioid use, suggesting that incretin pathway modulation may have time-dependent effects on postoperative pain physiology. These findings suggest a potential link between metabolic therapy and postoperative pain adaptation and warrant further investigation into the underlying mechanisms.
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