Does Ozempic cause muscle loss and how to prevent it?

Clinical trials have shown GLP-1 agonist drugs like semaglutide (Ozempic) can lead to a 13.9% loss of lean muscle mass (equal to a 6.9 kg or 15 lb) during treatment. Strategies to help prevent muscle loss include regular strength (resistance) training, aerobic exercise and adequate dietary protein, fluid and nutrient intake.

Do studies show muscle loss with Ozempic?

Yes, obesity trials have shown that participants using incretin mimetic agents like semaglutide (Ozempic, Wegovy) or tirzepatide (Mounjaro, Zepbound) lost 10% or more of their muscle mass in 68- to 72-week long clinical studies, which equates to roughly 20 years of muscle loss due aging, according to experts.

Studies have shown that patients who lose weight (fat mass) in clinical trials may also lose lean body mass, which includes muscle mass. Muscle makes up about 50% of lean body mass.

In the 68 week STEP-1 trial of semaglutide for the treatment of obesity, patients saw a 17.3 kg (38 lb) reduction in body weight with semaglutide, vs. a 2.7 kg (6 lbs) weight loss in the placebo group.

• Based on a Dual-Energy X-ray Absorptiometry (DXA) scan, patients also had a 6.9 kg (15.1 lb) mean reduction in total lean mass, vs. a 1.5 kg (3.3 lb) loss in the placebo group.
• Overall, 40% of the total weight loss in the semaglutide group was due to a reduction in lean body mass.

In a systemic review, the effects of semaglutide on lean body mass in obesity management were evaluated in 6 studies with 1,541 overweight or obese adults.

• Lean mass reductions were found to range from 0% to 40% of total weight reductions, and especially evident in larger studies.
• Even though lean mass was reduced in these studies, the amount of lean mass lost when compared to total body mass increased, suggesting a positive overall effect.
• The authors conclude that semaglutide affects weight loss primarily through fat mass reduction, but loss in lean mass leads to concerns, especially from larger clinical studies.

A small, retrospective review evaluated the clinical effectiveness of semaglutide (Ozempic) on weight loss, body composition and muscle strength in a Chinese population with obesity.

• Participants were prescribed semaglutide and results were compared to values from baseline after the patients had completed 24 weeks of treatment.
• Overall, weight was significantly reduced by 9.9 kg (21.8 lb) at 24 weeks. The proportion of patients with at least a 5% weight loss was 93% and with at least a 10% weight loss was 54%.
• However, a significant amount of skeletal muscle mass was also lost (1.4 kg or 3 lb), but this was found to be significantly less than the loss of fat mass at 5.6 kg (12.3 lb). By percentage, the fat mass loss was 15.6 ± 10.1%, and the muscle mass loss was 4.8 ± 4.4%, which was statistically significant.
• Muscle strength (measured by grip strength) did not change significantly, nor did calf circumference.

The manufacturer does not list muscle loss as a side effect in the FDA product labeling for Ozempic, made by Novo Nordisk. However, if you are starting treatment with a GLP-1 agonist such as semaglutide (Ozempic Wegovy), speak with your healthcare provider about preventing muscle loss with a resistance (strength) training program.

Also, consider meeting with a registered dietician (RD) who can provide information on how much protein you should eat per day and types of protein, your need for supplemental vitamins, and other nutritional strategies to help retain muscle mass and function.

Age-related loss of muscle mass can lead to reduced strength and physical function, a term often called sarcopenia. Sarcopenia may be associated with injury, falls, bone fractures and higher rates of death.

The long-term risks due to muscle loss when using incretin mimetic treatments like Ozempic are not fully known at this time. Clinicians and patients should work together to assess the benefits of blood sugar control, weight loss and heart protection against any risks associated with loss of muscle.

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How to prevent muscle loss with Ozempic?

The good news is that there are proven way to help maintain muscle strength if you are at risk of muscle loss.

• Engaging in strength (resistance) training and maintaining optimal levels of protein in your diet may help with muscle loss during Ozempic treatment.
• Studies have shown that resistance training can be effective to maintain muscle mass during weight loss in people with obesity or overweight.

Adequate nutrition and protein intake is also important to maintain muscle. The loss of skeletal muscle mass has been associated with calorie-restricted diets and rapid weight loss in general, as well as with use of incretin mimetic agents such as semaglutide (Wegovy, Ozempic) and tirzepatide (Zepbound, Mounjaro).

Factors that may contribute to muscle loss during weight loss in general, or with Ozempic treatment include:

• Appetite loss
• Loss of interest in eating
• Calorie restriction
• Low protein intake
• Pre-existing low muscle mass
• Low physical activity
• History of “yoyo dieting” (weight cycling)
• Older age
• Frailty
• Type 2 diabetes

Obesity occurring with type 2 diabetes or prediabetes may also be associated with lower muscle mass, and can lead to a more rapid decline in muscle mass in the older person.

To help maintain your muscle mass while taking Ozempic or other incretin mimetic agents like Wegovy, Mounjaro or Zepbound, you can:

• Do ongoing strength training (resistance training): Examples include lifting weights or using resistance bands, doing leg squats, push ups, or calf raises and use of gym machines.
• Eat adequate amounts of protein: Protein can be found in foods like eggs, lean meats (chicken, fish), low-fat dairy like cheese, cottage cheese, milk, or greek yogurt, tofu, and beans and legumes. The Institute of Medicine recommends 0.8 g/kg of body weight per day for healthy adults, with higher amounts suggested for people over 65 years of age. Protein needs are individual and should be recommended by your healthcare professional.
• Engage in aerobic and weight-bearing exercises: May include walking, jogging or running, stair climbing, gardening, hiking or dancing, depending upon your fitness level, age and health risk factors like arthritis, heart or lung disease. Check with your doctor before you start any exercise routine.
• Stay hydrated: The Institute of Medicine recommends adults drink 2 to 3 liters of water per day (about 8 to 12 cups). Your needs may be different, so ask your doctor or dietician.
• Education: Engage with your doctor, nurse and dietician to learn about the optimal nutrition plan for your weight-loss goals during Ozempic treatment.

Speak with your healthcare provider before you engage in a modified diet or exercise program and follow your medication dosing instructions exactly as prescribed by your doctor.

Do any medicines stop muscle loss with Ozempic?

Obesity treatments that work a new way may help to address muscle loss associated with incretin mimetic agents. Clinical studies on these agents are in early phases of investigation.

Eli Lilly, the manufacturer of the GLP-1 / GIP agonist tirzepatide (Mounjaro, Zepbound) has announced the development of bimagrumab (LY3985863), a monoclonal antibody that binds the activin/myostatin type II receptors ActRIIA and ActRIIB and blocks ligand binding.

In the BELIEVE Phase 2b study, bimagrumab is being studied alone and in combination with semaglutide in adults who are overweight or obese. The company states that combining these agents may further reduce fat mass while preserving muscle mass and lead to improved outcomes in obesity treatment.

This is not all the information you need to know about Ozempic (semaglutide) for safe and effective use and does not take the place of your doctor’s directions. Review the full product information and discuss this information and any questions you have with your doctor or other health care provider.

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