Comparative efficacy and safety of antidiabetic drugs for obese patients with knee osteoarthritis: a network meta-analysis of randomized controlled trials.

BACKGROUND: Obesity-related knee osteoarthritis (KOA) is a significant public health concern, affecting quality of life. Recent evidence suggests some antidiabetic drugs may help manage KOA in obese patients due to their anti-inflammatory and weight-reducing effects. OBJECTIVE: This study aimed to compare the efficacy and safety of antidiabetic drugs for managing pain and adverse events in obese KOA patients through a network meta-analysis of randomized controlled trials (RCTs). METHODS: A systematic search of multiple databases identified relevant RCTs on antidiabetic drugs for KOA. Treatment efficacy was assessed using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score improvement, and safety was evaluated based on the incidence of serious adverse events. The Surface Under the Cumulative Ranking Curve (SUCRA) scores were used to rank the treatments, and effect sizes were reported as mean differences (MD) with 95% confidence intervals (CI). RESULTS: A total of nine RCTs were included in the analysis. For pain relief, metformin demonstrated the largest effect size with a mean difference of - 1.13 (95% CI - 1.48, - 0.78) compared to usual care, followed by Metformin-Phosphatidylcholine (MFPH) (- 0.92, 95% CI - 1.70, - 0.13) and semaglutide (- 0.90, 95% CI - 1.48, - 0.32). In terms of safety, usual care exhibited the lowest risk of adverse events, with liraglutide (0.09, 95% CI - 0.74, 0.92) and semaglutide (0.21, 95% CI - 0.46, 0.88) also showing favorable safety profiles. The SUCRA rankings further supported these findings, with metformin ranking highest for efficacy (SUCRA: 86.8%) and usual care ranking highest for safety (SUCRA: 75.7%). However, these rankings should be interpreted alongside the effect sizes and clinical context to fully assess the trade-offs between efficacy and safety across interventions. CONCLUSIONS: Metformin and MFPH are promising for managing KOA pain in obese patients. Semaglutide offers a balanced efficacy and safety profile, while liraglutide may be a safe option for selected patients. Further research is needed to confirm these findings and assess long-term outcomes.