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 (I2) and heterogeneity (tau2) 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 (I₂ = 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.