Comparative Efficacy of Glucosamine-Based Combination Therapies in Alleviating Knee Osteoarthritis Pain: A Systematic Review and Network Meta-Analysis

Background: The lack of definitive scientific evidence sustains uncertainty about the efficacy of glucosamine and its combination therapies for knee osteoarthritis (KOA), contributing to an ongoing debate among clinical practice guidelines and healthcare practitioners. This systematic review and network meta-analysis (NMA) aimed to identify the most effective glucosamine combination therapy for KOA patients. Methods: Frequentist random-effects models were employed for this NMA, with standardized mean differences (SMDs) and 95% confidence intervals (CIs) calculated for primary outcomes. We incorporated an SMD value of 0.40 as a minimum clinically important difference (MCID) to interpret the pain outcome. Confidence in evidence was evaluated using CINeMA. Results: Thirty randomized controlled trials (RCTs) covering 5265 patients were included. Glucosamine with omega-3 (G + omega-3, SMD -2.59 [95% CI -4.42 to -0.75], moderate quality) and glucosamine with ibuprofen (G + ibuprofen, SMD -2.27 [95% CI -3.73 to -0.82], moderate quality) significantly reduced overall pain compared to placebo. Similarly, glucosamine + chondroitin sulfate + methylsulfonylmethane showed effectiveness in pain reduction (SMD -2.25 [95% CI -3.84 to -0.67], low-quality). None of the other interventions met the MCID threshold for overall pain reduction. Moreover, clustered ranking results showed that glucosamine with omega-3 interventions was more effective than others in reducing overall pain and adverse events. Conclusions: For KOA, combining glucosamine with omega-3 and ibuprofen effectively reduces pain and may lower NSAID side effects, improving treatment guidelines and decision-making for better patient care.