I heard that GLP-1 agonists are only effective as long as you are taking them. I believe this means weight lost is regained? Recently, I’ve also heard that part of the weight loss is muscle. In the situation of aging women (muscle loss overall, osteoporosis risk) and now with PCOS and insulin resistance, I’m curious about muscle wasting. GLP-1 agonists really seem like a short-term solution that capitalize on the obsession with weight loss in our culture but have a real risk for women longer-term.
—Anonymous
Nearly everyone who loses a significant amount of weight will lose muscle. This makes sense if you think about it. Carrying around more weight during your daily activities will result in more muscle. Imagine if you wore a 20-pound vest everywhere you went for several months. Then one day you stopped wearing the vest. Even if you made no other changes, some of the muscle you had built wearing the vest would be lost in the weeks after you stopped wearing it.
Does losing weight using GLP-1 agonists result in more muscle loss than in people who lose weight using other methods? Probably not. A meta-analysis of several studies of semaglutide (the active ingredient in Ozempic) found that loss of muscle mass varied greatly, from 0% to 40%, and that most of the weight loss seen in the trials that were included was fat and not muscle. In my practice, I have found that patients engaged in a strength-training program are less likely to lose muscle.
The data regarding what happens when people stop GLP-1 agonists is limited. There is a single clinical trial in which participants were randomized to either continue the highest dose of semaglutide or to stop semaglutide completely. In that trial — sponsored by Novo Nordisk, the company that holds the patent on, manufactures, and markets the drug — the participants regained weight.
We don’t have any clinical trials looking at a gradual reduction in dose or increased spacing of doses. Anecdotally, I do have patients who titrated off GLP-1 agonists and maintained their weight loss.
All that said, I would still say that GLP-1 agonists are not the right choice for everyone. However, in patients who have overweight or obesity and weight-related comorbidities such as prediabetes, high blood pressure, or high cholesterol, GLP-1 agonists are an important tool in an arsenal that until 2014 only included weight loss surgery.
The takeaway: While GLP-1 agonists are not for everyone, they are an important tool for people struggling with weight-related chronic illness. The concerns about muscle loss are not borne out in the literature.
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