Pediatric Research Update: Strategies to Minimize Muscle Loss When Using Anti-obesity Medications

Each month, the OMA Pediatric Committee reviews a pediatric-focused obesity research update to help keep you up to date about the latest findings. This month’s article explores strategies to prevent muscle loss during treatment with anti-obesity medications like Semaglutide or Tirzepatide, emphasizing the role of protein intake and resistance training in supporting long-term health.

Article Summary

Weight loss, in particular from medications such as Semaglutide or Tirzepatide, may lead to muscle loss which can in turn increase risk of weight regain, metabolic dysfunction, and reduced quality of life. While guidelines to mitigate this risk have not yet been developed, existing evidence suggests that adequate protein and micronutrient intake combined with resistance training may help to mitigate this risk.

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Article Review

Weight loss, whether it be due to bariatric surgery, lifestyle modifications, or anti-obesity medication, carries the risk of loss of skeletal muscle in addition to adipose tissue. In particular, there is concern that weight loss from glucagon like peptide-1 receptor agonists (also known as incretin-mimetic drugs (IMDs), including Semaglutide and Tirzepatide, due to the magnitude and speed of weight loss, can particularly place patients at risk for skeletal muscle loss, which can in turn slow metabolism, reduce strength and function, increase risk of weight regain, and impair quality of life. Indeed, in the pivotal trial that led to approval of Semaglutide for treatment of obesity in adults, 40% of the reduction in body weight was due to loss of lean mass, and while this includes all lean mass and not skeletal muscle, it is likely that skeletal muscle loss makes up a substantial portion of this. Similarly, in the pivotal trial that led to approval of Tirzepatide for treatment of obesity, the pooled treatment groups lost 10.9% of their lean mass, which overall is similar to the Semaglutide study when looking at overall percent of weight lost vs. lean mass. This is also comparable to prior studies evaluating lean mass loss following bariatric surgery or caloric restriction. However, there are several strategies that can help to mitigate this risk.

The authors of this review article acknowledge that there is a research gap regarding muscle loss from IMDs. But given the length of time necessary to complete long-term follow-up studies, the authors present recommendations that were discussed as part of a scientific roundtable meeting based on existing evidence.

It is well known that maintenance of muscle mass requires adequate macronutrient and micronutrient intake, and reduced caloric intake can lead to nutritional deficits and impair muscle maintenance and function. Thus, nutrition counseling plays a vital role in reducing the risk of muscle loss. Guidelines vary slightly for total protein intake recommendations, depending on age and other individual needs, but in general range from 0.8-1.5g/kg. Oral nutritional supplements are also suggested for patients who are not meeting protein and micronutrient intake goals. There are current studies evaluating the effect of oral nutritional supplements on muscle health in patients with obesity.

Resistance training has been found, through systematic reviews and meta-analyses, to help preserve muscle mass in patients with overweight or obesity who were undergoing caloric restriction, and thus can also be helpful in patients on anti-obesity medication. Indeed, there is evidence that IMD therapy plus exercise can reduce weight gain and return of cardiometabolic risk factors following discontinuation of IMD therapy. Current guidelines for physical activity for adults are 150-300 minutes per week of moderate- or 75-150 minutes of vigorous-intensity exercise with at least 2 sessions of muscle strengthening exercise including all of the major muscle groups.

Muscle mass can be estimated by various body composition methods, including MRI, CT, DXA, air displacement plethysmography, bioelectric impedance analysis, and anthropometric measurements. While imaging techniques are more accurate, their practicality in the clinical setting is more limited. Tests of muscle function (such as handgrip strength and sit-to-stand test) can also be used to assess muscle strength and physical function, which can be affected by muscle loss, particularly in older adults. More studies are needed regarding using body composition tests to guide IMD therapy.

It is widely recognized that obesity management should be undertaken with a multidisciplinary approach, incorporating nutrition and physical activity into each individualized plan. The importance of these lifestyle aspects in patients on IMDs is especially important, and can particularly be crucial to maintaining muscle mass, which can in turn help to increase the likelihood of long-term success.