Three-pronged approach helps preserve muscle mass during weight loss with GLP-1 medications, study finds
New findings to be presented at the European Congress on Obesity (ECO 2025) offer encouraging news for individuals living with overweight or obesity who are prescribed GLP-1 or dual GLP-1/GIP receptor agonists as part of their weight management plan. The six-month study involving 200 adults indicates that with the right support—specifically medical supervision, resistance training, and adequate protein intake—substantial fat loss can be achieved with only minimal reductions in lean muscle mass.
The research, conducted by a team of obesity specialists based in New York, reinforces a growing body of evidence supporting the efficacy of GLP-1-based therapies for treating obesity and highlights key strategies for protecting muscle mass during weight loss.
Understanding GLP-1 Receptor Agonists
GLP-1 (glucagon-like peptide-1) receptor agonists—such as semaglutide and liraglutide—were initially developed to treat type 2 diabetes but have also demonstrated significant benefits in supporting weight loss and managing obesity.
GLP-1 is a type of incretin hormone, produced in the gut, that helps regulate blood glucose levels. Medications in this class work by mimicking or enhancing the effects of the body’s own GLP-1, thereby:
- Stimulating insulin secretion in response to food,
- Inhibiting glucagon release (a hormone that raises blood sugar),
- Slowing gastric emptying,
- Suppressing appetite by promoting satiety.
More recently, medications such as tirzepatide, which activate both GLP-1 and GIP (glucose-dependent insulinotropic polypeptide) receptors, have received approval for the treatment of type 2 diabetes and/or obesity. These dual agonists may offer even greater benefits by acting on multiple hormonal pathways involved in appetite and metabolism.
Why Body Composition Matters in Weight Management
While many treatments focus on reducing total body weight, experts stress the importance of maintaining lean muscle mass during weight loss. Muscle plays a vital role in metabolism, mobility, and long-term health. Excessive muscle loss during weight reduction can result in weakness, reduced physical function, and negative metabolic consequences.
To address this, the New York-based research team conducted a six-month prospective cohort study designed to monitor body composition changes in individuals prescribed GLP-1 or dual GLP-1/GIP receptor agonists.
Study Design and Methods
The study enrolled 200 adults aged 18 to 65 years, all of whom had a BMI of 25 kg/m² or higher—placing them in the overweight or obesity category. Participants were prescribed either semaglutide (a GLP-1 receptor agonist) or tirzepatide (a dual GLP-1/GIP receptor agonist). Sixty percent (n = 120) received tirzepatide, while the remaining 40% (n = 80) were given semaglutide.
All participants received care from a board-certified obesity medicine physician, who provided structured guidance on medication adherence, resistance training, and dietary protein intake. Body composition was assessed using the InBody 570—a medical-grade device employing multi-frequency bioelectrical impedance analysis (BIA)—at baseline, three months, and six months.
The InBody 570 measures a range of indicators including total body water, fat mass, skeletal muscle mass, visceral fat, and segmental muscle distribution. Researchers also collected data on medication adherence, physical activity, and dietary patterns throughout the study period.
Importantly, all 200 participants (99 men and 101 women) completed the full study duration.
Key Results: Fat Loss Outpaces Muscle Loss
The average participant age was 47 years, with a mean baseline BMI of 31.4 kg/m².
After six months:
- Women reduced their average body weight from 71 kg (156 pounds) to 62 kg (137 pounds)—a 12% decrease. On average, they lost 10.8 kg of fat mass while losing just 0.63 kg (1.4 pounds) of muscle.
- Men decreased their weight from 101 kg (223 pounds) to 88 kg (193 pounds)—a 13% reduction. Fat mass decreased by 12 kg (25 pounds), while muscle loss averaged just 1 kg (2.4 pounds).
Participants reported high adherence to medication protocols—95% at three months and 89% at six months. Qualitative feedback revealed that those who consistently followed resistance training and protein intake recommendations were more successful in retaining muscle mass and strength.
Comparing Semaglutide and Tirzepatide
While analysis is still underway to examine the comparative effects of semaglutide and tirzepatide on fat and muscle loss, early findings suggest both medications are highly effective in supporting body fat reduction in people living with obesity.
The researchers noted that although some muscle loss is expected during weight loss, targeted interventions—especially when supervised by a qualified obesity medicine specialist—can significantly reduce this loss.
Crucially, the combination of medication adherence, adequate dietary protein, and strength-based exercise emerged as a powerful trio for preserving muscle.
Expert Commentary: Insights and Cautions
Dr Dinabel Peralta-Reich and Dr Alexandra Filingeri, co-authors of the study, shared key insights with Medical News Today.
“This study measured body composition—specifically body fat mass (in pounds), muscle mass (in pounds), and total body weight (in pounds)—in patients at baseline, 3 months, and 6 months while taking GLP/GIP weight loss medications,” they explained.
“The results suggest that, with proper supervision, a protein-rich diet, regular resistance training, and guidance from a trained medical provider, patients can decrease fat mass while minimising muscle loss.”
Dr Peralta-Reich further emphasised:
“We found that, under close supervision and regular follow-up from an obesity medicine specialist, patients were able to lose fat mass with only a minimal decline in muscle mass.”
Commenting on the broader implications, Dr Mir Ali, a board-certified general and bariatric surgeon not involved in the study, added:
“This study was helpful to show that some muscle [loss] can occur with significant weight loss.”
“We see this in our surgical weight loss patients as well, and try to emphasise methods to minimise muscle loss.”
He continued:
“When patients are taking these weight loss medications, they should also implement measures to reduce muscle loss. Muscle loss can lead to weakness and other problems.”
“The main things patients can do is ensure adequate protein intake and exercise. Resistance-type exercises are helpful in maintaining and possibly even building muscle.”
Dr Filingeri noted that the research aimed to provide a clearer understanding of how incretin medications influence fat and muscle mass:
“We found that, under close supervision and regular follow-up from an obesity medicine specialist, patients were able to lose fat mass with only a minimal decline in muscle mass.”
However, she stressed the importance of context when interpreting the findings:
“These results cannot be generalised to patients receiving medication via telemedicine without routine body composition analysis, nor can they be generalised to in-person visits without utilising body composition analysis.”
She concluded by highlighting the need for further studies:
“Further research should explore the roles that diet and exercise play in the success of these medications.”
Conclusion: A Pathway to Safer, Healthier Weight Loss
This six-month investigation provides meaningful insights for clinicians and individuals living with obesity who are using GLP-1 or dual GLP-1/GIP receptor agonists as part of their weight loss journey. By incorporating medical supervision, resistance training, and adequate protein intake, it is possible to minimise the loss of lean muscle and support long-term health outcomes.
As the obesity epidemic continues and these medications become more widely used, tailored, evidence-based strategies like those outlined in this study will be essential to ensuring that weight loss is both effective and sustainable.
CCH Insight:
One of the concerns about AOMs is that large amounts of muscle mass may be lost when people shed weight rapidly, so the results of this study are re-assuring, demonstrating that with the right diet and exercise, lean muscle loss can be minimised. The study is also an excellent reminder that these medications should be taken as an adjunct to lifestyle changes, including a healthy diet and physical activity. With appetite being significantly restricted, it is important to eat a nutrient-dense diet to ensure adequate intake of all essential nutrients, including protein.
