Evidence to support the efficacy of glucosamine for osteoarthritis is mixed, and any benefits are small. A Cochrane systematic review performed a meta-analysis of data from 20 RCTs: 17 trials compared glucosamine with placebo, and four trials compared glucosamine with a nonsteroidal anti-inflammatory drug (NSAID; ibuprofen in three trials and piroxicam in one trial). Sixteen RCTs evaluated the knee exclusively, two evaluated osteoarthritis at multiple sites, and two did not specify the location. When data from all studies were pooled, glucosamine was found to be more effective than placebo with respect to pain and function. However, subgroup analyses of the 10 RCTs in which allocation was adequately concealed, found that glucosamine was not more effective than placebo for relieving pain, stiffness, or function. Another subgroup analysis found that the glucosamine sulfate product made by the Rotta Pharmaceutical Company was more effective than placebo, while other glucosamine preparations (glucosamine sulfate and glucosamine hydrochloride) failed to show a benefit. The reasons for the differences in results are unknown, but may include differences in the products (there is no common standard for their manufacture), differences in the trial methods (e.g. different outcome measures), and differences in the methodological quality of the studies, including susceptibility to bias (most of the positive, and few of the negative, trials were funded by manufacturers of glucosamine). The health economics analysis conducted by the National Institute for Health and Clinical Excellence (NICE) concluded that glucosamine is not currently cost-effective for the NHS.

• Sources of evidence:
• NICE looked at studies that investigated the efficacy and safety of glucosamine with respect to symptoms, function, and quality of life in adults with osteoarthritis. Due to the large volume of evidence found, trials with a sample size of less than 40 were excluded.
• A Cochrane review and two additional RCTs published subsequently were appraised.
• The Cochrane review (20 RCTs, n = 2596) investigated the effectiveness and safety of glucosamine in people with osteoarthritis [Towheed et al, 2005]. Literature searches were performed up to January 2005 and included osteoarthritis of different sites (16 RCTs used knee, two RCTs used multiple sites, and for two RCTs the site was not specified). All the trials included were of glucosamine sulfate, except one which was of glucosamine hydrochloride.
• Glucosamine compared with placebo:
• Analyses including all the studies found that glucosamine reduced pain compared with placebo. However, analyses restricted to the RCTs with adequate allocation concealment found no significant difference between glucosamine and placebo in pain and WOMAC function scores. In two RCTs (n = 414), there was a statistically significant difference in minimum joint space width favouring glucosamine; but in one RCT (n = 212) there was no difference in mean joint space width.
• In terms of safety, no significant difference in adverse events was found between glucosamine and placebo:
• Number of participants reporting adverse events in 14 RCTs: RR 0.97 (95% CI 0.88 to 1.08).
• Glucosamine compared with oral NSAIDs:
• Glucosamine was found to significantly reduce pain (measured on a visual analogue scale; VAS) compared with NSAIDs in people with osteoarthritis of the knee:
• Summary pooled standardized mean difference (SMD) in three RCTs: –0.40 (95% CI –0.60 to –0.19).
• Regarding harms, glucosamine was less likely than NSAIDs to produce adverse reactions:
• Number of participants reporting adverse events in four RCTs: RR 0.29 (95% CI 0.19 to 0.44).
• One RCT published subsequently compared four interventions (glucosamine hydrochloride [1500 mg/day], chondroitin sulfate [1200 mg/day], combined chondroitin sulfate with glucosamine hydrochloride, and placebo) over 24 weeks in people (n = 1583) with osteoarthritis of the knee [Clegg et al, 2006].
• No significant difference was found between glucosamine and placebo in the proportion of people with a 20% decrease in WOMAC pain score at 24 weeks.
• A second RCT in people (n = 325) with osteoarthritis of the knee compared glucosamine sulfate (1500 mg/day), paracetamol, and placebo in a 6-month treatment phase [Herrero-Beaumont et al, 2007].
• Significant changes were found in favour of glucosamine sulfate compared with placebo in terms of the Lequesne Index and WOMAC function scores.
• When economically evaluating the role of glucosamine, the NICE Guideline Development Group concluded that:
• For glucosamine sulfate, evidence to support its efficacy was not strong enough to warrant recommending that it should be prescribed on the NHS.
• For glucosamine hydrochloride, evidence to support its efficacy as a symptom modifier was poor and, because only one product is licensed, it would not be cost effective to prescribe glucosamine on the NHS — NICE regarded measurement of joint-space narrowing as of questionable value.

[National Collaborating Centre for Chronic Conditions, 2008]