Glucosamine, chondroitin sulfate, and the two in combination for painful knee osteoarthritis

Clegg DO, Reda DJ, Harris CL, et al. · The New England Journal of Medicine

Neither glucosamine, chondroitin, nor the combination beat placebo on the primary endpoint (20% WOMAC pain reduction). Against a 60.1% placebo response, glucosamine was 3.9 percentage points higher (p=0.30), chondroitin 5.3 (p=0.17) and the combination 6.5 (p=0.09). The trial could detect an effect when there was one: celecoxib, the active comparator, responded 10.0 percentage points above placebo (p=0.008). In the prestratified moderate-to-severe pain subgroup — 70 to 72 patients an arm — the combination responded 79.2% against 54.3% on placebo (p=0.002), and celecoxib did not separate there (69.4%, p=0.06).

Population

US adults with symptomatic knee osteoarthritis (GAIT trial)

Intervention

Glucosamine HCl 1500 mg/day, chondroitin sulfate 1200 mg/day, or both, for 24 weeks; celecoxib 200 mg/day as active comparator

Comparator

Placebo

Limitations

Overall null. The often-quoted combination benefit is one exploratory subgroup of 72 patients against 70 on placebo, and the authors present it as exploratory rather than as a finding. Used glucosamine hydrochloride, not the sulfate salt used in positive European trials. High placebo response (60.1%), which the paper's own assay sensitivity argues is a real placebo effect rather than an insensitive instrument, since celecoxib cleared it.