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A study published in Nature Medicine looks at a drug to preserve lean body mass during weight loss with tirzepatide.
Dr Brendan Gabriel, Senior Lecturer at the Rowett Institute of Nutrition and Health, University of Aberdeen, said:
“Skeletal muscle is a critical tissue for long term health. Not only is it necessary for enabling movement and preventing frailty as we age, but it also stores the majority of sugar after we eat, meaning it is a key tissue in preventing diabetes and cardiovascular disease. As we age, many people lose muscle mass which can lead to poorer health outcomes. Recent advances in obesity therapies are extremely effective at reducing fat mass. But a substantial portion of weight loss during treatment comes from lean mass, including skeletal muscle. This is normal during weight loss, and there is no clear evidence that obesity drugs reduce muscle more than dieting, however strategies which can achieve fat loss while preserving lean mass and muscle mass should be beneficial for long term health outcomes.
“This current study is a robust randomised control trial, generally considered the gold standard for this type of therapeutic intervention. The biology behind this current therapeutic has been studied by muscle biologists for almost 3 decades, so it is a logical therapeutic target, but recent advances have made it possible to develop more effective and specific therapies. It is quite exciting in this trial that Apitegromab was able to preserve lean mass. Lean mass is often used as a proxy for muscle mass, however it’s important to note that is does not measure muscle directly, and the authors do acknowledge this in the study. Muscle strength is an important functional outcome of potentially preserved muscle mass, and very important for preventing frailty and falls during ageing.
“The authors found no significant differences in grip strength or sit-to-stand tests in this trial, which may be due to the relatively short trial, or it could be because lean mass is not accurately capturing muscle mass in this study. Muscle contributes to insulin sensitivity due to its ability to store sugar, however, in this study the authors did not see any improvements in insulin sensitivity. This may be due to the relatively short-term nature of the study.
“Additionally, the type of therapeutic here – a monoclonal antibody – can be effective is some but not all clinical situations and may not be as widely suitable for as many people as other obesity therapeutics have been. However, for people living with sarcopenic obesity – a condition in which muscle mass is being lost faster than normal – this could be a promising treatment.”
Dr Marie Spreckley, Prevention of Diabetes and Related Metabolic Disorders in High Risk Groups, University of Cambridge, said:
“These are promising phase 2 findings from a randomised, double-blind, placebo-controlled trial evaluating whether lean mass can be preserved during tirzepatide-induced weight loss. The study enrolled 102 adults with overweight or obesity and found that participants receiving apitegromab alongside tirzepatide lost significantly less lean mass than those receiving tirzepatide plus placebo, despite achieving similar overall weight loss.
“At 24 weeks, participants receiving apitegromab lost approximately 1.9 kg less lean mass than those receiving placebo. Lean mass accounted for 14.6% of total weight loss in the apitegromab group compared with 30.2% in the placebo group, while fat mass accounted for 85.3% and 69.5% of total weight loss, respectively. These findings suggest that apitegromab may improve the composition of weight loss by preserving lean mass while maintaining similar overall weight reduction.
“This is an important area of research because substantial weight loss, whether achieved through medication, dietary interventions or bariatric surgery, is often accompanied by some loss of lean mass. Strategies that help preserve lean mass while maintaining the benefits of weight reduction are of considerable interest, but whether they improve longer-term health outcomes remains to be established.
“The study was generally well designed, and the authors appropriately acknowledge its limitations. The trial was relatively small, predominantly female, and excluded people with diabetes and clinically significant cardiometabolic disease. Physical activity was not objectively measured, which could potentially influence body composition outcomes, and the study was not designed to assess longer-term effects.
“Importantly, although apitegromab preserved lean mass, the study did not demonstrate clear improvements in physical function or cardiometabolic outcomes over the 24-week treatment period. Preserving lean mass is biologically plausible and potentially beneficial, but larger and longer studies will be needed to determine whether these changes translate into meaningful improvements in strength, physical function, quality of life, or long-term health outcomes.
“Overall, this study provides important proof-of-concept evidence that selective myostatin inhibition may help improve the composition of weight loss during tirzepatide treatment. However, these findings should be viewed as encouraging early evidence rather than definitive proof of clinical benefit, and confirmation in larger phase 3 trials will be important.”
‘Apitegromab for lean mass preservation during tirzepatide-induced weight loss: a randomized, double-blind, placebo-controlled phase 2 trial’ by Richard E. Pratley et al. was published in Nature Medicine at 16:00 UK time on Monday 8 June 2026.
DOI: 10.1038/s41591-026-04440-4
Declared interests
Dr Brendan Gabriel: “Senior Lecturer at the Rowett Institute of Nutrition & Health, University of Aberdeen. My research on skeletal muscle metabolism, obesity, and type 2 diabetes is funded by the British Heart Foundation, BBSRC, EASTBIO, EFSD, the Novo Nordisk Foundation, and NHS Grampian Charities. The Novo Nordisk Foundation is an independent charitable foundation with no involvement in or influence over my research.”
Dr Marie Spreckley: “Dr Marie Spreckley is a postdoctoral researcher at the University of Cambridge specialising in obesity, nutrition and weight management research. She declares no personal financial interests, consultancy agreements, advisory roles, speaker fees, stock ownership, honoraria, or pharmaceutical industry employment related to incretin-based therapies.”