Ozempic, Wegovy, Mounjaro, and other glucagon-like peptide-1 receptor agonists (GLP-1s) have quickly become household names in just a few short years. Between individuals with chronic conditions like type 2 diabetes and individuals with obesity, GLP-1s are now being used by over 12 percent of people in America—62 percent of which use GLP-1s to manage chronic conditions like diabetes or heart disease, and 40 percent use these medications to manage their weight (Montero, 2024). However, what many herald as a “miracle drug” is now increasingly associated with negative side effects—one of the latest of which is muscle loss, or sarcopenia.
GLP-1s and muscle loss: what the data shows
GLP-1s are relatively new to the weight loss space. While we know these medications are effective, we don’t have enough data to paint a clear picture of how GLP-1s can impact overall long-term health—especially for those with a variety of health conditions that may interact differently with these drugs. The evidence around GLP-1s and sarcopenia is often conflicting, with some studies finding no change to skeletal muscle mass, while others indicate accelerated muscle degradation due to rapid weight loss (Uchiyama, 2023; Hong, 2019). One literature review reported that up to 50 percent of weight loss from GLP-1s was not from fat loss, but a reduction in muscle mass and other vital body tissues (Sargeant, 2019).
Despite the inconsistent findings, what we do know is that rapid weight loss does not exclusively apply to fat. Other forms of expedited weight loss, such as highly restrictive dieting, are known to reduce both fat and fat-free mass (muscle, bone, organs, and other non-fat tissues) (Cava, 2017). In the context of GLP-1s, we can safely assume that the average 15 percent weight loss induced by the drug is likely to cause some muscle loss, potentially leading to poorer treatment outcomes—especially for older adults (Wilding, 2021).
“Falls cause 95 percent of hip fractures, so loss of muscle is a serious concern, because as muscle mass goes down, the risk of imbalance—and hence falls—goes up,” says Dr. Mary O’Connor (Wagar, 2010). ”We cannot overlook how devastating hip fractures can be to patients and families—over one in five hip fracture patients dies within the first year after fracture (Downey, 2019).”
“Falls cause 95 percent of hip fractures, so loss of muscle is a serious concern, because as muscle mass goes down, the risk of imbalance—and hence falls—goes up,” says Dr. Mary O’Connor, Chief Medical Officer at Vori Health.
The double-edged sword facing employers and payers
The employers and payers who cover GLP-1s face mounting pressures to manage treatment risks while also meeting the demands of their employees and plan members. While helping members achieve a healthier weight now can improve outcomes and prevent high-cost care down the road, many are left playing a game of whack-a-mole to mitigate the side effects of weight loss drugs—some of which can be just as serious as the risks associated with obesity.
Employees and members suffering from muscle loss due to GLP-1s may be more likely to experience:
- Fractures. Strong muscles, bones, and other non-fat tissues are essential to preventing musculoskeletal (MSK) injuries. Without a strong MSK network supporting healthy movement, individuals are at a higher risk for skeletal injuries which can drive up the cost of care.
- Frailty. On a higher level, a weak MSK system can make an individual feel frail and unstable, especially for older adults who are already at risk for osteoporosis. Muscle loss creates a compounding effect that multiplies an individual’s fall risk and discourages movement—which only further exacerbates muscle loss.
- Sarcopenic obesity. When an individual undergoes rapid weight loss, the ratio between fat and muscle can increase past what is considered healthy. Even with a lower overall weight, an individual with more fat than muscle, known as sarcopenic obesity, is at risk for insulin resistance, cardiovascular disease, immobility, and other serious—and costly—health conditions (Roh, 2020).
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Mitigating the risks of GLP-1s with whole-person care
There’s no question that GLP-1s are a powerful solution for weight loss. But what’s often missed is the fact that these medications are a tool, not the whole toolbox. This is especially when it comes to caring for individuals who are experiencing both obesity and muscle and joint pain. Because pain can inhibit mobility, people with MSK concerns are already at risk for muscle loss—particularly women, for whom many studies draw an underlying connection between female sex, low muscle mass, and knee osteoarthritis (Smith, 2020).
Given the risks of accelerated weight loss associated with GLP-1s, every individual who has an MSK condition and takes these medications should be supervised by a holistic physician-led team that specializes in MSK care. Behavior and lifestyle modifications–including healthy movement, targeted physical therapy exercises, nutrition counseling, and health coaching–are key to sustaining weight loss while also preventing the unwanted side effects of these medications.
Measuring the impact of exercise
One study comparing different maintenance strategies for weight loss (exercise, GLP-1s, or a combination of both) found that participants who were treated with a combination of GLP-1 and supervised exercise for one year maintained a lower weight compared to those who only took a GLP-1 (Jensen, 2024). Moreover, those treated with the exercise-only protocol maintained their weight loss more successfully (average 2.5 kg regained) than those with the GLP-1-only protocol (average 6.0 kg regained) (Jensen, 2024).
But not all exercises are created equally when it comes to combating the risk of muscle loss. At Vori Health, our physical therapists working with individuals taking GLP-1s prioritize resistance-training exercises. “So many patients are surprised by how quickly they can build muscle with the right kind of exercises. Weights and resistance bands are fantastic to incorporate, as well as exercises that use your body weight like squats,” says Tessy Oommen, PT, DPT a physical therapist at Vori. Building muscle mass is key for not only preventing other chronic conditions, but also keeping the weight off, as individuals with more muscle mass burn more calories at rest.
"So many patients are surprised by how quickly they can build muscle with the right kind of exercises. Weights and resistance bands are fantastic to incorporate, as well as exercises that use your body weight like squats,” says Tessy Oommen, PT, DPT a physical therapist at Vori.
Boosting results with nutrition counseling and health coaching
Evidence-based nutrition guidance is also critical to help GLP-1 patients prioritize diets that lower inflammation, promote muscle growth, and help individuals maintain a healthy weight. “As GLP-1s work their wonders, our dietitians and health coaches help patients rebuild better foundations,” says Rusti Quarles, lead health coach at Vori. “We’re there for every step to set smart nutrition goals, nurture new exercise habits, and combat the daily stressors in life that often cause setbacks.“
“As GLP-1s work their wonders, our dietitians and health coaches help patients rebuild better foundations,” says Rusti Quarles, lead health coach at Vori.
A one-stop shop for better GLP-1 and MSK care
At Vori Health, we know that GLP-1s are a key ingredient in many weight loss success stories. But we also know that navigating the risks of these drugs, and making and sustaining these lifestyle changes, can be overwhelming. That’s why Vori’s care team approach surrounds individuals with 360-degree support, providing the necessary doctor-led medical care, physical therapy, nutrition guidance, and health coaching to optimize every patient’s outcomes. Our personalized approach and convenient online and in-person appointments tailors every MSK program to the needs of the individual, providing the right care to encourage movement, enhance MSK strength, and help patients taking GLP-1s build healthier habits for life.
Want to learn more? Schedule a demo to discover how Vori Health’s doctor-led, whole-person MSK care can improve outcomes and lower health risks for your members taking GLP-1 medications.
REFERENCES
- Montero, 2024: Montero A, Sparks G, Presiado M, Hamel L. KFF Health Tracking Poll May 2024: The Public’s Use and Views of GLP-1 Drugs. KFF.
- Uchiyama, 2023: Uchiyama S, Sada Y, Mihara S, Sasaki Y, Sone M, Tanaka Y. Oral Semaglutide Induces Loss of Body Fat Mass Without Affecting Muscle Mass in Patients With Type 2 Diabetes. J Clin Med Res. 2023;15(7):377-383.
- Hong, 2019: Hong Y, Lee JH, Jeong KW, Choi CS, Jun HS. Amelioration of muscle wasting by glucagon-like peptide-1 receptor agonist in muscle atrophy. J Cachexia Sarcopenia Muscle. 2019;10(4):903-918.
- Sargeant, 2019: Sargeant JA, Henson J, King JA, Yates T, Khunti K, Davies MJ. A Review of the Effects of Glucagon-Like Peptide-1 Receptor Agonists and Sodium-Glucose Cotransporter 2 Inhibitors on Lean Body Mass in Humans. Endocrinol Metab (Seoul). 2019;34(3):247-262.
- Cava, 2017: Cava E, Yeat NC, Mittendorfer B. Preserving Healthy Muscle during Weight Loss. Adv Nutr. 2017;8(3):511-519.
- Wilding, 2021: Wilding JPH, Batterham RL, Calanna S, et al. Once-Weekly Semaglutide in Adults with Overweight or Obesity. N Engl J Med. 2021;384(11):989-1002.
- Roh, 2020: Roh E, Choi KM. Health Consequences of Sarcopenic Obesity: A Narrative Review. Front Endocrinol (Lausanne). 2020;11:332.
- Jensen, 2024: Jensen SBK, Blond MB, Sandsdal RM, Olsen LM, Juhl CR, Lundgren JR, Janus C, Stallknecht BM, Holst JJ, Madsbad S, Torekov SS. Healthy weight loss maintenance with exercise, GLP-1 receptor agonist, or both combined followed by one year without treatment: a post-treatment analysis of a randomised placebo-controlled trial. eClinicalMedicine. 2024;69:102475.
- Wagar, 2010: Scott V, Wagar L, Elliott S. In Victoria Scott Consulting ed. , ed. Falls and related injuries among older Canadians: fall‐related hospitalizations & intervention initiatives. Prepared on behalf of the Public Health Agency of Canada. Victoria, BC, Canada: Division of Aging and Seniors; 2010.
- Downey, 2019: Downey C, Kelly M, Quinlan JF. Changing trends in the mortality rate at 1-year post hip fracture - a systematic review. World J Orthop. 2019 Mar 18;10(3):166-175. doi: 10.5312/wjo.v10.i3.166. PMID: 30918799; PMCID: PMC6428998.
- Smith, 2020: Stephanie L. Smith, James Woodburn, Martijn P.M. Steultjens, Sex- and osteoarthritis-related differences in muscle co-activation during weight-bearing tasks, Gait & Posture, Volume 79, 2020.
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