Risk of Bias and Brand Explain the Observed Inconsistency in Trials on Glucosamine for Symptomatic Relief of Osteoarthritis: A Meta‐Analysis of Placebo‐Controlled Trials

Objective To determine whether study sponsor, chemical formulation, brand of glucosamine, and/or risk of bias explain observed inconsistencies in trials of glucosamine's efficacy for treating pain in osteoarthritis (OA). Methods A systematic review and stratified meta‐analysis of randomized placebo‐controlled trials was performed, and random‐effects models were applied with inconsistency (I 2 ) and heterogeneity (tau 2 ) estimated using Review Manager and SAS, respectively. The major outcome was reduction of pain; the standardized mean difference (SMD [95% confidence interval (95% CI)]) served as effect size. Results The inclusion criteria yielded 25 trials (3,458 patients). Glucosamine moderately reduced pain (SMD −0.51 [95% CI −0.72, −0.30]), although a high level of between‐trial inconsistency was observed (I 2 = 88%). The single most important explanation (i.e., covariate) was brand, reducing heterogeneity by 41% ( P = 0.00032). Twelve trials (1,437 patients) using the Rottapharm/Madaus product resulted in significant pain reduction (SMD −1.07 [95% CI −1.47, −0.67]), although a sensitivity analysis of 3 low risk of bias trials using the Rottapharm/Madaus product showed less promising results (SMD −0.27 [95% CI −0.43, −0.12]), which is only a small effect size. Thirteen trials (1,963 patients) using non–Rottapharm/Madaus products consistently failed to show a reduction in pain (SMD −0.11 [95% CI −0.46, 0.24]). The second most important explanation was overall risk of bias (reducing heterogeneity by 32%). Conclusion Most of the observed heterogeneity in glucosamine trials is explained by brand. Trials using the Rottapharm/Madaus glucosamine product had a superior outcome on pain in OA compared to other preparations of glucosamine. Large inconsistency was found, however. Low risk of bias trials, using the Rottapharm/Madaus product, revealed a small effect size.