Obesity and Diabetes — 11

And that’s not all. There is consternation about GLP-1-induced loss of muscle mass and the potential development of “sarcopenic obesity” (meaning general loss of muscle mass and strength). Reports are mixed, with some suggesting the incidence is as high as 40 percent and others using magnetic resonance imaging claiming it’s a nonissue. It is confounded by the fact that significant weight loss without medication also leads to reduction in skeletal muscle mass. No matter, loss of muscle mass does occur in many people, and some have advocated an increased dietary ingestion of protein and strength training to counter these possible side effects. Nevertheless, this remains an important issue. The companies that make these drugs are acquiring or partnering with companies that have drugs in clinical trials with GLP-1 drugs to preserve or increase muscle mass, such as bimagrumab, apitegromab, or azelaprag, and many others are in development. In the meantime, those considering starting a GLP-1 drug may want to get a baseline DEXA scan in order to track their muscle mass.

While there have been concerns about loss of bone density with GLP-1 drugs, a randomized trial in people with increased risk of fracture reported the changes in bone turnover and mass was due to the loss of weight and mechanical loading, not the drug. Results from another randomized trial reinforced the benefit of exercise while taking GLP-1 drugs for achieving optimal bone health metrics.

In my mind, the biggest drawback of GLP-1 drugs—“forever drugs”—is the potential need for a lifetime commitment. For whatever reason, it is difficult to follow through on that commitment. Most people taking GLP-1 drugs stop them in the first year. Randomized trials have shown that stopping the drugs leads to regaining the weight, and we have not seen any commitment from the manufacturers to identify or test an exit strategy. While the current dependence on once-a-week injections will be replaced by pills that simulate the GLP-1 effect in the near term, that still means lifelong therapy. Colleagues of mine who specialize in bariatric medicine say that’s fine—it’s just like giving insulin to a diabetic or blood pressure medicine to a person with high blood pressure. While the analogy is easy to understand, there are still unknowns about GLP-1 drug side effects at high doses in the long term—the longest follow-up we have for obesity is four years. If the risk of sarcopenic obesity is real, then the number of frail people with increased risk of falling would substantially increase. What’s even more disconcerting is that much of the obesity pandemic is in children: an indeterminate, and perhaps lifelong, commitment to taking a drug from a young age is troubling, to say the least.