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Unraveling the Truth Behind GLP-1 Medications and Muscle Loss

Updated: Jan 15


I recently spoke with a concerned patient who told me that their primary care provider told them to “immediately stop taking semaglutide” because they were going to disproportionately lose muscle if they continued with the prescribed treatment, and even went as far as to assert that 50% of the weight lost would be muscle mass. While this bold assertion suggests an obvious lack of knowledge regarding the mechanism of action for these medications, I couldn’t help but wonder if this provider gives this same warning to their patients with Type 2 Diabetes who they undoubtedly prescribe these medications for on a daily basis (GLP1 medications being one of the most effective pharmacological tools for lowering Hemoglobin A1c values). Still, there have been many recent discussions surrounding GLP-1 medications, and concerns have arisen about their potential association with muscle loss. 

GLP-1 medications work by activating Glucagon-like-peptide (GLP1) receptors in our bodies, which leads to a more sensitive and amplified release of our own naturally-occurring GLP1 hormone. This release leads to a myriad of metabolic benefits, a prominent benefit being that of weight loss, and has no direct effect on our muscle mass. While some data may suggest a link between GLP-1 drugs and muscle reduction, a closer examination reveals a more nuanced perspective. Many studies which show some reduction in lean mass do not take into account the effects of dietary restriction, which is more likely to be associated with a loss of both lean and fat mass. In this blog post, I delve into various studies to uncover the complex relationship between GLP-1 medications and changes in muscle mass.

Positive Trends in Body Composition:

In studies like STEP 1 and SUSTAIN 8, the overall proportion of lean mass to total body mass increased, indicating an improvement in body composition. Despite initial concerns, these findings suggest that the use of GLP-1 drugs might contribute to positive changes in lean mass.

Insights from the SURMOUNT-1 Tirzepatide Study:

Data from the SURMOUNT-1 tirzepatide study provided more optimistic conclusions. It reported a significant drop in fat mass (33% to 36%) and lean mass (10% to 11%) among participants, depending on their age group. While acknowledging a portion of the weight loss was lean mass, these results underscore the complexity of the relationship between GLP-1 medications and muscle changes.

Semaglutide-Specific Studies:

Semaglutide-related studies present mixed findings. The STEP study revealed that placebo recipients experienced minimal changes in body composition, while those receiving semaglutide showed reductions in both fat and muscle. However, the proportion of lean body mass improved in the drug arm. SUSTAIN 8 further compared semaglutide with canagliflozin, a sodium-glucose cotransporter type 2 diabetes drug, finding similar changes in fat mass, lean mass, and visceral fat mass. This suggests that it’s not the GLP1 drug class alone but also the SGLT2-i drug class which can cause a reduction in body mass including both fat and muscle.

Conflicting Data on Muscle Mass:

The discussion intensifies with conflicting data on GLP-1 and muscle loss. A 2020 network meta-analysis suggested marked decreases in fat-free mass with semaglutide and other GLP-1 receptor agonists compared to a placebo. On the contrary, a 2023 Chinese study found that semaglutide maintained muscle mass. Earlier data even hinted at a potential protective effect of GLP-1 receptor agonists against muscle wasting.

The Bottom Line:

In summary, GLP-1 drugs effectively aid weight loss, particularly in reducing fat, and may have protective benefits for muscle mass.  Notably, studies like STEP 1 and SUSTAIN 8 reveal a significant portion of weight loss as lean mass, but a broader examination of various studies suggests an overall enhancement in body composition and potential protective effects against muscle wasting for many patients. In our own clinical experience, we have seen great benefits to body composition when patients heed proper clinical guidance such as consuming adequate amounts of protein, exercising regularly, and promoting muscle preservation with supplements such as Coenzyme Q10 and others. 

Additionally, GLP-1 drugs may contribute to a reduced risk of cardiovascular-related death, heart attack, and stroke. They also help to lower blood pressure, improve cholesterol levels, reverse fatty liver disease, and prevent Type  2 Diabetes. An additional  literature review highlights variations in the proportion of lean body mass reductions (ranging from 20% to 50% of total weight lost), aligning with patterns observed in diet-induced weight loss and bariatric surgery. GLP1 medications have many benefits that may outweigh the risks, especially as a safer alternative to bariatric surgery. 


In conclusion, some degree of lean muscle mass loss is normal in most weight loss scenarios, as the body tends to shed both fat and some lean tissue when losing weight. It is important to weigh the risks and benefits with an experienced provider before beginning any treatment regimen for weight loss. 

Madeline Haws, FNP-C


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