It may not just be fat you are losing...
Some of the weight lost from GLP-1 RAs may come from muscle- a reminder that quality, not quantity of weight-loss is what's important.
Not all weight-loss is the same, and a recent article published in The Atlantic helps point out some of the issues regarding the use of GLP-1 RAs to the extent that some patients may lose weight derived from muscle along with fat.
As these GLP-1 RAs become more popular and more prescribed there should be growing concerns over possible side effects related to taking these medications.
However, in this case it’s not necessarily a side effect of the drug, but instead it’s possible that the appetite-suppressing nature of GLP-1s and changes in dietary intake may unfortunately lead to muscle loss as the body scours for whatever source of calories it can find when in a deficit. As people begin to eat less they may source fewer protein-rich foods, which may also contribute to loss in muscle.1
This effect may not be severe in average adults, but in people who may be more susceptible to muscle loss or may already be weak (such as the elderly) the effects can be rather detrimental.
The Atlantic provides the following remarks:
The newest and much-hyped obesity drugs are, at their core, powerful appetite suppressants. When you eat fewer calories than you burn, the body starts scavenging itself, breaking down fat, of course, but also muscle. About a quarter to a third of the weight shed is lean body mass, and most of that is muscle.
Muscle loss is not inherently bad. As people lose fat, they need less muscle to support the weight of their body. And the muscle that goes first tends to be low quality and streaked with fat. Doctors grow concerned when people start to feel weak in everyday life—while picking up the grandkids, for example, or shoveling the driveway. Taken further, the progressive loss of muscle can make patients, especially elderly ones who already have less muscle to spare, frail and vulnerable to falls. People trying to slim down from an already healthy weight, who have less fat to spare, may also be prone to losing muscle. “You have to pull calories from somewhere,” says Robert Kushner, an obesity-medicine doctor at Northwestern University, who was also an investigator in a key trial for one of these drugs.
In this case, there’s a concern that the rapid muscle loss, a phenomenon named sarcopenia, may lead to fatigue and difficulty engaging in strenuous activity. For instance, a survey conducted with Japanese elderly2 who were on GLP-1 RAs noted a higher risk of falling as compared to those who weren’t on these medications, suggesting a possible heightened risk of harm in the elderly and more feeble.
In one article cited by The Atlantic3 they also make the following remarks:
Weight loss with semaglutide and tirzepatide is accompanied by favorable reductions in body fat [1••, 2••]. However, it is also accompanied by reduced lean body mass [1••, 2••, 45, 69, 70], which may influence factors that contribute to body weight regulation and other health outcomes. Lean body mass (LBM) is considered a significant driver of metabolic rate, with a reduction in lean tissue partially contributing to reduced daily energy expenditure [34]. The reduction in LBM may also influence the tonic drive to eat, which may further contribute to influences on body weight regulation [71]. Reduced LBM may be of additional clinical importance given its association with decreased bone mineral density and increased risk of fractures, as well as its relation to metabolic function (e.g., insulin sensitivity) and aerobic capacity [72, 73]. Adults 65 years and older are at increased risk of sarcopenia, characterized by an age-related decrease in skeletal muscle mass, with accompanying losses of strength and physical function [74, 75].
Again, muscle loss may be a typical consequence of various weight-loss processes. It’s also worth noting that the role of GLP-1 RAs and lean mass loss is not clear, as some evidence suggests a protective role against muscle wasting and sarcopenia in select mouse models and human studies.4
However, what may surprise readers is that doctors appear to be offering a solution in case of muscle loss- eat more protein and engage in resistance training:
Doctors currently offer two pieces of standard and unsurprising advice to protect people taking obesity drugs against muscle loss: Eat a high-protein diet, and do resistance training. These recommendations are perfectly logical, but their effectiveness against these drugs specifically is unclear, John Jakicic, a professor of physical activity and weight management at the University of Kansas Medical Center, told me. He is now surveying patients to understand their real-world behavior on these drugs.
This comment is extremely bizarre since, for all intents and purposes, wouldn’t a better diet and resistance training already help with weight management? As in, if you were to make these changes wouldn’t you also lose weight anyways? It’s quite strange how often recommendations for GLP-1 RAs tend to come with factors that would already be critical in weight management.
For now, the mixed evidence should suggest that we should be more on the lookout for clear evidence of muscle wasting and sarcopenia related to GLP-1 RAs, but raise concerns that those who are more affected by GLP-1 RAs may be more at risk of detrimental effects after taking these drugs.
And of course, it seems as if there is already a possible solution in the making to help with some of these side effects- by pairing GLP-1 RAs with other treatments that can help protect from muscle wasting:
Meanwhile, drug companies are already thinking about the next generation of weight-loss therapies. “Wouldn’t it be great to have another mechanism that's moving away from just appetite regulation?” Haines said. Companies are testing ways to preserve—perhaps even enhance—muscle during weight loss by combining Wegovy or Zepbound with a second muscle-boosting drug. Such a combination could, in theory, allow patients to lose fat and gain muscle at the same time.
[…]
Pairing bimagrumab with an existing obesity drug could potentially maximize the weight loss from both. Losing weight tends to get harder over time; as you lose muscle, your body burns fewer calories. A drug that minimizes that muscle loss—or even flips it into muscle gain—could help patients boost the amount of energy their body expends, while Wegovy or Zepbound suppresses calories consumed. The mechanisms of how this might actually work in the body still need to be understood, though. Previous studies of bimagrumab found that patients grew more muscle, but they didn’t necessarily become faster or stronger. Haines, who is planning a small study of her own with bimagrumab, is most interested in how the combination affects not the structural but the metabolic functions of muscle.
The solution to a possible pharma side effect is, of course, more drugs!
I’m not sure how well this will map our as it seems that this is a mere hypothesis, but it speaks greatly to how pharmaceutical companies perceive the common people and how willing they are to take as many medications as possible.
Consider that comments were made at the end of 2023 that obese patients should be provided both GLP-1 RAs as well as bariatric surgery for even better weight-loss possibilities:
Remember that weight-loss is not something that should happen by an “any means necessary” approach. How and what weight is being loss are just as important than the mere act of weight-loss.
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As an aside, when researching the twin vegan study it was reported that one twin who was on a vegan diet lost a greater deal of muscle mass as compared to the omnivore twin. There were also instances in which one of the vegan twins lost so much weight that the researchers encouraged him to eat more.
SHIN IKEJIMA, SEIYA KONDO, TAKENORI SAKAI, HISANORI TANIAI, TOMOMI TAKAHASHI, JUNKO UMEZU, MAMI ISEKA, MAYA INOUE, HARUMI NISHIHARA, KAZUYA MURATA, AIZAN HIRAI; Novel Approach to Sarcopenia in Diabetic Patients Treated with GLP-1 Receptor Agonists (GLP-1RA). Diabetes 1 July 2018; 67 (Supplement_1): 673–P.
Wadden, T.A., Chao, A.M., Moore, M. et al. The Role of Lifestyle Modification with Second-Generation Anti-obesity Medications: Comparisons, Questions, and Clinical Opportunities. Curr Obes Rep 12, 453–473 (2023). https://doi.org/10.1007/s13679-023-00534-z
Mellen, R. H., Girotto, O. S., Marques, E. B., Laurindo, L. F., Grippa, P. C., Mendes, C. G., Garcia, L. N. H., Bechara, M. D., Barbalho, S. M., Sinatora, R. V., Haber, J. F. D. S., Flato, U. A. P., Bueno, P. C. D. S., Detregiachi, C. R. P., & Quesada, K. (2023). Insights into Pathogenesis, Nutritional and Drug Approach in Sarcopenia: A Systematic Review. Biomedicines, 11(1), 136. https://doi.org/10.3390/biomedicines11010136
I lost 23 lbs since August and lost some muscle also - need to start resistance training - thanks for reminding. (no ozempic used)
Wow, that's important to know.