Even so, he says, “I remain cautious about immediate widespread adoption of semaglutide for knee OA, given the absence of long-term data on structural joint outcomes and the risk of weight regain after treatment cessation.”
Anita Wluka, PhD, FRACP, MBBS, a professor of public health and preventive medicine at Monash University, Melbourne, Australia, agrees that the trial helps fill some gaps in understanding how to achieve enough weight loss to yield a significant impact on pain in patients with knee OA. She questions, though, whether rapid weight gain after stopping semaglutide may affect joint pain more than gradual weight gain, given the reduced time available for a remodeling of the knees’ biomechanics. In other words, weight regained too rapidly may outpace the ability of the knee joints to adjust, exacerbating the pain. The rapid weight gain also may hurt patients’ morale, she cautions.
Given those limitations and the unknown long-term effects, Dr. Wluka says, “I may consider conservative therapy with exercise and dietary change in the first instance, despite their limited efficacy.”
Although the trial’s self-reported measures of pain and function didn’t allow for an investigation of semaglutide’s underlying mechanism of action, Dr. Bliddal maintains the results clearly point to weight loss as a key factor in alleviating patients’ knee pain. “We know that it makes a world of difference for the actual symptoms,” he says.
If used to achieve and maintain significant weight loss over a longer period, Dr. Bliddal says the drug may even help slow degradation of the knee joint. “By this, you would either avoid or postpone a possible replacement of the joint, which is a very important matter,” he says. Total knee replacements don’t last indefinitely and especially for younger patients with knee OA, delaying the replacement could prevent more complicated revisions in the future. Whether semaglutide can forestall that surgery, however, will require further research.
Bryn Nelson, PhD, is a medical journalist based in Seattle.
References
- Lim YZ, Wong J, Hussain SM, et al. Recommendations for weight management in osteoarthritis: A systematic review of clinical practice guidelines. Osteoarthr Cartil Open. 2022 Dec 1;4(4):100298.
- Bliddal H, Bays H, Czernichow S, et al. Once-weekly semaglutide in persons with obesity and knee osteoarthritis. N Engl J Med. 2024 Oct 31;391(17):1573–1583.
