Semaglutide and fat lean mass
Do These Popular Weight Loss Shots Cause Lean Body Mass Loss?
This concern is dominating some of the discussions on using GLP-1 agonist receptor medications such as Wegovy® and Ozempic®. These drugs are FDA-approved forms of semaglutide, a peptide that helps improve diabetes and leads to substantial weight loss.
This new drug class is the most effective weight loss drug to date. It has the highest weight loss to the safety profile of any FDA-approved drug.
But the rumor is "these shots lead to a loss of muscle mass," so, therefore, maybe not that helpful. A popular podcaster who is also a doctor, has stated that in his practice these GLP-1 drugs are leading to mainly muscle loss and, therefore, not that helpful.
I call BS.
Let's talk about body composition briefly. A scale tells you a weight which is only helpful when we consider other things such as body height, muscle mass, and fat mass. Tools to tell us fat vs. lean mass (nonfat mass) or fat vs. lean mass (muscle or muscle and bones) are used to determine if fat is lost or gained, muscle is lost or gained.
There are various tools such as ultrasound, electrical impedance, water displacement, calipers, and a form of X-ray. They each have pros and cons but they are all much more accurate than a scale.
Let's look at the peer-reviewed, published clinical studies:
178 participants with type 2 diabetes underwent DXA scanning (a type of x-ray that is considered the gold standard for measuring fat vs. lean muscle mass/weight) and were treated with metformin and either semaglutide, canagliflozin or placebo for one year. At the end of the trial, those in the active treatment groups lost weight, but both fat mass and muscle mass declined.
That may sound concerning, and it is the fodder for rumors that these drugs lead to loss of muscle mass. But in reality, this was very favorable toward muscle and lean mass preservation. When someone is heavy and loses weight, their muscle mass generally drops because it takes less muscle mass to carry a lighter body (in the absence of deliberate exercise).
In this study, the % of lean mass increased because they lost significantly more fat than lean mass. This was a favorable outcome, even though there was a small amount of lean mass lost.
Another study included 1,961 adults without diabetes and with a BMI > 27 and one co-morbidity or a BMI of greater than 30 (BMI=Body mass index. BMI > 27= Overweight. BMI > 30 = Obese. Comorbidity= weight-related disease such as hypertension).
To restate, when someone loses weight, if they lose more fat than lean mass, this improves their body composition favorably. This study was for 68 weeks, and a subgroup was followed with DXA scanning to assess fat vs muscle loss. They found substantial losses of fat mass, and an increase in the percentage of lean muscle mass, even though they did lose some muscle mass.
A third study evaluated the use of semaglutide on weight loss and measured strength, fat mass, waist circumference, and fat-free (lean) mass. This study was for 26 weeks.
They found the fat mass declined, waist circumference declined, strength remained the same, and the percentage of fat-free mass improved.
I can find no study supporting the claim by podcasters, bloggers, and internet experts that support the claim that semaglutide has an unfavorable effect on lean body mass as a percentage of total body weight.
So why is this claim popular?
There can be a few reasons.
First, follow the money. There is about to be a new drug released that causes a gain in muscle mass while reducing fat mass. It is not out yet (bimagrumab), but it leads to weight loss and slight increases in lean mass in a 48-week clinical trial.
Second, follow the bias. If you are a doctor with a strong opinion on a particular diet pattern or the best way for weight loss, a drug that disrupts that belief is a problem. It takes a while for biases to be dropped in favor of something that may upend your views (which were right in the first place). This may lead to "finding cracks in the armor" of something new.
Third, controversy sells. Semaglutide for weight loss has been an enormous hit; very safe and effective and tough to get at first. If a story leaks that it isn't all it is cracked up to be, this is the story that sells, over reinforcement of the status quo.
In summary, weight loss, whether from dieting, bariatric surgery, semaglutide, or fasting, can lead to insignificant lean mass loss, but the lean mass ratio generally improves in a favorable fashion. There may be drugs down the road that paradoxically improve lean mass in actual lbs while causing fat loss, and we will address those when they are available.
The clinical outcomes of semaglutide on weight loss go beyond the improved body composition. In addition to weight loss (mostly fat), this drug also has cardiovascular benefits, and in individuals with cardiovascular risk, it appears to extend the healthy life span by 1.7 years (over conventional treatments).
Effects of once-weekly semaglutide vs. once-daily canagliflozin on body composition in type 2 diabetes: a substudy of the SUSTAIN 8 randomized controlled clinical trial. Diabetologia (2020) 63:473–485. Rory J. McCrimmon et al.
Adipose Tissue, Appetite, and Obesity INTEGRATED PHYSIOLOGY OF OBESITY AND METABOLIC DISEASE. Journal of the Endocrine Society. Volume 5, Issue Supplement 1, April-May 202 A17. J Wilding et al.
Once-Weekly Semaglutide Induces an Early Improvement in Body Composition in Patients with Type 2 Diabetes: A 26-Week Prospective Real-Life Study. Nutrients 2022, 14, 2414. Sara Volpe et al.
Effect of Bimagrumab vs Placebo on Body Fat Mass Among Adults With Type 2 Diabetes and Obesity A Phase 2 Randomized Clinical Trial. JAMA Network Open. 2021;4(1):e2033457
Estimated Life-Years Gained Free of New or Recurrent Major Cardiovascular Events With the Addition of Semaglutide to Standard of Care in People With Type 2 Diabetes and High Cardiovascular Risk Diabetes Care 2022;45:1211–1218 | https://doi.org/10.2337/dc21-1138. Jan Westerink