Individuals using GLP-1 receptor agonists (RAs) are at increased risk for nutritional deficiencies and loss of lean muscle mass in the absence of dietary support, a systematic review of 12 studies has found.

Although GLP-1 RAs are increasingly prescribed for weight loss and type 2 diabetes, evidence-based nutritional strategies to support their safe and effective use are limited, wrote Marie Spreckley, PhD, a weight-management specialist and researcher at the University of Cambridge, United Kingdom, and colleagues.

GLP-1 RAs have “the potential to revolutionize obesity and type 2 diabetes care,” Spreckley told Medscape Medical News. However, because the drugs significantly suppress appetite, concerns have arisen about possible vitamin and mineral deficiencies and insufficient protein intake, as well as loss of lean muscle mass.

The study, published online in Obesity Reviews, showed the need for better integration of dietary strategies with use of GLP-1 RAs, she said.

Lean Muscle Loss Sparks Concern

The researchers searched five databases to identify peer-reviewed studies published between January 2015 and April 2025 that involved adults with obesity or type 2 diabetes who took either semaglutide or tirzepatide and that included an active dietary intervention or measured nutrition-related outcomes. Twelve studies met their criteria: 10 randomized trials, one nonrandomized comparative study, and one cross-sectional observational study.

Study interventions ranged from structured very low-energy or ketogenic diets to general lifestyle counseling and observational dietary assessments.

Across studies, patients’ energy intake decreased by 24%-39% overall, and lean tissue loss accounted for up to 40% of total weight loss. Five studies involved structured nutrition plans in addition to GLP-1 RAs. In these studies, use of nutritional programs (such as a keto diet in one study) were associated with greater preservation of fat-free muscle mass.

Only three studies involved dietitians, and systematic assessment of protein or micronutrient intake was rare, the researchers wrote. The cross-sectional observational study, in which patients completed 3-day food records to assess nutrient intake, showed widespread nutritional deficiencies, low protein intake, and inadequate vitamin and mineral intake, Spreckley told Medscape Medical News.

“This highlights a major disconnect between the introduction of these medications for the management of obesity and type 2 diabetes and nutritional care to support patients taking them,” she said. 

The researchers expected that the appetite-suppressing effects of GLP-1 RAs would significantly reduce energy intake and lead to lean mass loss, consistent with previous studies of obesity management medication and bariatric/metabolic surgery, said corresponding author Adrian Brown, PhD, a principal research fellow and associate professor in nutrition and dietetics at University College London.

“The findings underscore the need for routine dietitian involvement in obesity and type 2 diabetes care when prescribing obesity management medications,” Brown told Medscape Medical News. “Clinicians should aim to prioritize higher-protein (1.2-1.6 g per kilogram of adjusted body weight), nutrient-dense diets to preserve lean mass, and monitor for vitamin and mineral deficiencies such as vitamin D, iron, and B₁₂.”

Robust Trials Necessary

The studies included in the review were limited by several factors, including small sample sizes in several studies, short follow-up periods, and a lack of standardized nutrition protocols in studies of nutritional adequacy in patients using the weight-loss medications, Spreckley said. In addition, few studies monitored or assessed diet quality or micronutrient status, and high-risk groups such as older adults and those with sarcopenic obesity were underrepresented, she noted.

Future research should include large-scale randomized controlled trials comparing structured dietary interventions with usual care using validated diet quality measures, and should incorporate advanced body composition imaging, such as MRI, and biochemical monitoring, Spreckley said. Cost-effectiveness analyses of integrated nutrition support are also needed, she said.

Until high-quality studies are performed that can establish optimal dietary strategies, “clinicians should adopt a holistic multidisciplinary, collaborative, and patient-centered approach that includes nutritional expertise alongside medical and behavioral care,” the authors wrote. “Dietitians should be engaged from the outset to deliver individualized dietary advice to manage common gastrointestinal side effects and ensure adequate intake of key vitamins and minerals through dietary counseling and supplementation where needed.”

W. Timothy Garvey, MD, professor of medicine in the Department of Nutrition Sciences at the University of Alabama at Birmingham, agreed that more research is needed.

“Future research should address both the active phase of weight loss, when patients are hypocaloric, and the maintenance phase of weight loss, when patients are consuming adequate calories to maintain their new lower level of body weight,” Garvey, who was not involved in the study, told Medscape Medical News. “Intake of protein, iron, and calcium, for example, would be of particular concern.”

Studies tied to longer-term health outcomes, including mobility/functionality, falls, fractures, bone health, and cardiovascular disease risk factors, will be needed, he added.

“The clear majority of patients in phase 3 clinical trials of GLP-1-based medications and patients who have undergone bariatric surgery experience increased functionality and quality of life such that loss of muscle mass does not appear to be a clinical problem,” Garvey told Medscape Medical News.

Still, the current study’s emphasis on the need to address loss of lean mass is important, he said.

“More research in needed regarding direct measurements of muscle volume and fat-free muscle volume, and how this translates into muscle performance, particularly in select populations such as the elderly, those with sarcopenia, and postmenopausal women,” Garvey said.

The study was supported by the UK National Institute for Health and Care Research (NIHR), with additional support from the UK Medical Research Council (MRC) and the NIHR University College London Hospitals Biomedical Research Centre. Brown disclosed researcher-led grants from the NIHR, Rosetrees Trust, MRC, INNOVATE UK, British Dietetic Association, British Association for Parenteral and Enteral Nutrition, Biotechnology and Biological Sciences Research Council, the UK Office for Health Improvement and Disparities, and NovoNordisk. Brown also reported honoraria from Novo Nordisk, Lilly, Office for Health Improvement and Disparity, Johnson & Johnson, and Obesity UK unrelated to the current study, as well as serving on the Medical Advisory Board and being a shareholder of Reset Health Clinics Ltd. Garvey disclosed no financial conflicts of interest.