Effectiveness of Combined Glucosamine and Chondroitin Sulfate Therapy in Knee Osteoarthritis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Background. Glucosamine and chondroitin sulfate are widely used symptomatic slow-acting drugs for osteoarthritis; however, their efficacy remains controversial.
Objective: to evaluate the efficacy of combined glucosamine and chondroitin sulfate therapy in knee osteoarthritis through a systematic review and meta-analysis of randomized controlled trials.
Materials and methods. A systematic search of Medline, EMBASE, Cochrane Library, and PubMed databases was conducted covering 2000–2024. Eligible studies were randomized controlled trials of duration ≥8 weeks comparing glucosamine and/or chondroitin sulfate with placebo in symptomatic knee osteoarthritis. Quality was assessed with Cochrane RoB 2.0 and Newcastle–Ottawa tools. Random-effects meta-analysis (DerSimonian–Laird method) was used to calculate pooled standardized mean differences (SMD) with 95% confidence intervals.
Results. Seventeen studies (n = 6,198) were included. The mean age of participants was 60.5 ± 10.1 years; 68.6% were women. The mean treatment duration was 34.7 ± 33.3 weeks. Combined therapy was associated with statistically significant improvements versus placebo in visual analogue scale pain (SMD -0.180; 95% CI: from -0.271 to -0.089; p < 0.001; I² = 81.7%) and WOMAC function (SMD -0.170; 95% CI: from -0.254 to -0.086; p < 0.001; I² = 78.1%). The safety profile was similar to placebo. Egger’s test did not detect publication bias (p >0.10).
Conclusion. Combined glucosamine and chondroitin sulfate therapy provides statistically significant but clinically small improvements in pain and function for knee osteoarthritis. The effect size is small (SMD <0.2) but may be clinically relevant for selected patients given the favorable safety profile.

For citation: Budko AA, Akulkina LA, Fedorinova EE, Berzegova TK, Matysik VB. Effectiveness of combined glucosamine and chondroitin sulfate therapy in knee osteoarthritis: A systematic review and meta-analysis of randomized controlled trials. Therapy (Moscow). 2026;12(5S):94–103.
https://doi.org/10.18565/therapy.2026.5-s5.94-103

INTRODUCTION

Knee osteoarthritis (OA) is one of the most common degenerative musculoskeletal disorders, affecting approximately 250 million people worldwide [1]. It is characterized by low-grade synovial inflammation, progressive degradation of articular cartilage, subchondral sclerosis, and osteophyte formation, resulting in pain, functional limitations, and impaired quality of life [2].

Symptomatic slow-acting drugs for osteoarthritis (SYSADOAs), including glucosamine and chondroitin sulfate, have an important place in OA treatment guidelines. Glucosamine is an amino sugar and a precursor of glycosaminoglycans that stimulates proteoglycan synthesis by chondrocytes [3]. Chondroitin sulfate is a major structural component of the cartilage extracellular matrix and has anti-inflammatory properties [4]. Glucosamine contributes to the synthesis of glycosaminoglycans and proteoglycans in the cartilage matrix and may also exert anti-inflammatory effects through inhibition of NF-κB [5]. As a structural component of cartilage, chondroitin sulfate may stimulate type II collagen and aggrecan synthesis while inhibiting degradative enzymes [6]. Their combined use may produce a synergistic effect by targeting different mechanisms involved in OA pathogenesis.

Despite the widespread clinical use of glucosamine and chondroitin sulfate, evidence regarding their efficacy remains conflicting. A large meta-analysis by Wandel S. et al. (2010) concluded that these agents did not provide a clinically meaningful benefit [7], whereas Cochrane systematic reviews by Singh J.A. et al. (2015) reported statistically and clinically significant improvements with their use [8, 9]. These discrepancies may reflect methodological differences across studies, including differences in product quality, patient selection criteria, and follow-up duration [10]. Given the limited number of treatments with established efficacy for chronic OA pain and the adverse effects associated with their long-term use, the search for safe pharmacologic options remains important.

The aim of this study was to conduct a systematic review and meta-analysis of randomized controlled trials (RCTs) evaluating the efficacy of combination therapy with glucosamine and chondroitin sulfate for knee OA using rigorous methodological criteria and current reporting standards.

MATERIALS AND METHODS

Study design and protocol registration

This systematic review and meta-analysis was conducted in accordance with the PRISMA 2020 guidelines [11].

Search strategy

A systematic search of MEDLINE (via PubMed), Embase, the Cochrane Central Register of Controlled Trials (CENTRAL), and the Cochrane Database of Systematic Reviews was performed for the period from January 2000 through December 2024. The search strategy included terms related to knee OA, glucosamine, chondroitin sulfate, and RCTs. The reference lists of the included studies and relevant systematic reviews were also examined.

Eligibility criteria

Inclusion criteria:

• • RCTs;
• • participants with knee OA diagnosed according to the American College of Rheumatology criteria;
• • use of glucosamine and/or chondroitin sulfate as the intervention;
• • comparison of glucosamine and/or chondroitin sulfate with placebo or another active control;
• • follow-up of at least 8 weeks;
• • use of validated outcome measures: the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), the Visual Analog Scale (VAS) for pain, the Lequesne index, or the Knee injury and Osteoarthritis Outcome Score (KOOS);
• • publication in English or Russian.

Exclusion criteria:

• • uncontrolled studies;
• • use of other structure-modifying agents;
• • incomplete data for the primary outcomes;
• • duplicate patient populations;
• • studies at high risk of bias.

Study selection and data extraction

Two reviewers independently screened titles and abstracts and assessed the full texts of potentially eligible articles. Disagreements were resolved by consens...

A.A. Budko, L.A. Akulkina, E.E. Fedorinova, T.K. Berzegova, V.B. Matysik