Evaluation of efficacy and safety of Glucosamine sulfate, Chondroitin sulfate, and their combination regimen in the management of Knee Osteoarthritis: A systematic review and meta-analysis
Authors: Rabade Anvita , Viswanatha Gollapalle Lakshminarayanashastry , Nandakumar Krishnadas , Kishore Anoop 
Published: September 2023

Aim: This study was aimed to assess the efficacy and safety of oral Symptomatic Slow Acting Drugs for Osteoarthritis (SYSADOAs) such as Glucosamine Sulfate, Chondroitin Sulfate, and their combination regimen in the management of knee osteoarthritis (KOA).
Methods: This systematic review was conducted according to PRISMA 2020 guidelines. A detailed literature search was performed from 03/1994 to 31/12/2022 using various electronic databases including PubMed, Embase, Cochrane Library, and Google Scholar using the search terms- Glucosamine sulfate, Chondroitin sulfate, Knee osteoarthritis, Joint pain, Joint disease, and Joint structure for literature concerning glucosamine, chondroitin, and their combination in knee osteoarthritis treatment. Cochrane Collaboration’s Risk assessment tool (version 5.4.1) was used for assessing the risk of bias and the quality of the literature. The data was extracted from the included studies and subjected to statistical analysis to determine the beneficial effect of Glucosamine Sulfate, Chondroitin Sulfate, and their combination.
Results: Twenty-five randomized controlled trials (RCTs) were included [9 RCTs are exclusively for Glucosamine sulfate, 13 RCTs are exclusively for Chondroitin sulfate, and only 3 RCTs can be considered for assessing the possible benefits of the combination of Glucosamine sulfate (GS) and Chondroitin sulfate (CS) versus Placebo]. The results of this meta-analysis revealed the following: (1) Pain intensity: Chondroitin sulfate showed a significant reduction in pain intensity, (2) Physical function: Chondroitin sulphate showed a significant improvement in physical function; (3) Joint space narrowing: Glucosamine sulfate showed a significant reduction in tibiofemoral joint space narrowing. Their combination did not reduce pain intensity and showed no improvement in the physical function, whereas it showed a non-significant reduction in joint space narrowing. In the safety aspect, both compounds have a good safety profile and are well tolerated.
Conclusion: When the overall effect of these SYSADOAs was evaluated, it was seen that they reduced pain intensity and improved physical function showing their symptom-modifying action and decreased the joint space narrowing significantly showing their disease-modifying action. In the safety aspect, both compounds have a good safety profile and are well tolerated. This meta-analysis revealed that as individual drugs glucosamine sulfate showed a significant reduction in the joint space narrowing while chondroitin sulfate showed a significant reduction in pain intensity and improvement in the physical function. This meta-analysis also showed that the combination did not significantly improve the symptoms or modify the disease. This may be because of the availability of limited trials on the combination of the sulfate forms of the intervention. Thus, further trials on the effect of glucosamine sulfate and chondroitin sulfate are required to establish accurate evidence regarding their use in KOA.