Four major medical organizations have released comprehensive nutritional guidance for clinicians prescribing glucagon-like peptide-1 receptor agonists for obesity treatment. These guidelines address growing concerns about medication adherence, side effects, and long-term efficacy. The American College of Lifestyle Medicine, American Society for Nutrition, Obesity Medicine Association, and The Obesity Society published the joint advisory, which establishes evidence-based nutritional priorities to support GLP-1 therapy for obesity management.

Key Clinical Challenges Identified

Glucagon-like peptide-1 receptor agonists (GLP-1s) reduced body weight by 5% to 18% in clinical trials and have demonstrated multiple clinical benefits, though effects in real-world analyses have been lower. Challenges include gastrointestinal side effects; nutritional deficiencies due to caloric reduction; loss of muscle and bone mass; low long-term adherence with subsequent weight regain; and high costs with resulting low cost-effectiveness.

Adherence in real-world settings is substantially lower than in trials. In manufacturer-sponsored trials, adherence has ranged from 83% to 88% at 66 to 68 weeks. In practice, adherence rates range from 33% to 50% at 1 year and approximately 15% at 2 years.

Weight regain following discontinuation is common. As much as two-thirds of the weight lost may be regained within 1 year, even when conventional nutritional counseling and behavioral therapy accompany treatment.

Nutritional and Metabolic Complications

Patients using GLP-1s to treat obesity experience significant reductions in appetite and energy intake, with observed caloric reductions of 16% to 39%. This rapid reduction may result in inadequate intake of essential micronutrients, particularly when energy intake is less than 1200 kcal/d for females and less than 1800 kcal/d for males.

In the STEP 1 trial, participants lost an average of 13.6 kg, of which 8.3 kg (62%) was fat mass and 5.3 kg (38%) was lean body mass. Because muscle accounts for approximately half of lean body mass, these results correspond to a muscle loss equivalent to approximately 20% of the total weight lost.

Substantial and rapid weight loss—defined as at least 14% over 3 to 4 months—has been associated with loss of bone mineral density. More moderate and gradual weight reduction may better preserve bone health. The advisory recommends dual-energy x-ray absorptiometry scanning every 1 to 2 years when feasible to monitor lean mass and bone health.

Comprehensive Assessment Framework

Before initiating GLP-1 therapy, a complete medical and nutritional assessment—including documentation of weight history, goals, and medical conditions that may affect nutritional status—is recommended.

All patients should be screened for current or prior eating disorders, including binge eating disorder, anorexia nervosa, bulimia nervosa, and night eating syndrome. Because the effects of GLP-1s on eating disorders are not well established and may vary, a history of restrictive eating disorder is a general contraindication. Those who screen positive should be referred to both an obesity medicine specialist and an eating disorder specialist before initiating therapy.

Evidence-Based Nutritional Interventions

The recommended dietary allowance of protein for adults is 0.8 g/kg/d; however, higher intake targets of 1.2 to 1.6 g/kg/d have been proposed during periods of weight reduction.

The advisory emphasizes that increased protein intake alone is unlikely to preserve muscle mass without concurrent resistance training. Patients should be encouraged to engage in at least three weekly sessions of strength training, along with 150 minutes per week of moderate-intensity aerobic activity. Excess protein beyond tissue repair or growth needs may be converted to fat and stored as visceral adipose tissue.

Management of Gastrointestinal Side Effects

Nausea, vomiting, constipation, and diarrhea are common adverse effects during dose titration and may interfere with continued use. To support adherence, clinicians should recommend prevention and management strategies.

Smaller, more frequent meals and temporary avoidance of high-fat or high-fiber foods may alleviate symptoms. Patients who reduce food intake due to nausea may exacerbate symptoms and further reduce nutritional intake. Structured eating—such as a small breakfast followed by meals every 3 to 4 hours, accompanied by adequate fluid intake—is advised.

Health Equity Considerations

Disparities in access to GLP-1s have been documented by race, ethnicity, and socioeconomic status. In a study of 1.2 million commercially insured US patients with diabetes (2015 to 2019), lower rates of GLP-1 use were observed among Asian, Black, and Hispanic patients, and among those in lower-income households, compared with White patients and higher-income groups.

Nationally representative data indicate that approximately 51% of U.S. adults meet FDA eligibility criteria for semaglutide.  The data also show that Black (57%) and Hispanic (55%) adults have higher eligibility, but barriers such as lack of insurance, regular providers, income, or education may limit access in these groups.

Food as Medicine Integration

Food is Medicine (FIM) programs are nutrition interventions delivered within health care settings. They are prescribed by clinicians, tailored by registered dietitian nutritionists (RDNs), and may be covered by insurance.

FIM programs may address barriers to healthful eating such as cost, time, access, and knowledge. While most studies have not targeted weight loss as a primary outcome, modest reductions in BMI (0.4 to 0.6 kg/m²) have been observed. These programs may support improved outcomes with GLP-1 therapy and are identified as an important area for further research.

Cost-Effectiveness Implications

The U.S. list price of GLP-1s for obesity treatment ranges from $12 000 to $16 000 annually. Patients without insurance coverage may bear the full cost, though manufacturer discounts may lower prices to $7000 to $8000 per year.

Multiple analyses indicate that GLP-1s do not meet accepted thresholds for cost-effective therapy (e.g., less than $150 000 per quality-adjusted life-year [QALY] gained), even at discounted rates. Nonindustry-sponsored studies estimate costs per QALY gained from $237 000 to $483 000.

Implementation Recommendations

Despite the effectiveness of GLP-1s for weight reduction, long-term success is limited by gastrointestinal side effects, risks of nutrient inadequacy and musculoskeletal loss, costs, low adherence, and weight regain.

Clinicians should establish a comprehensive care plan that includes multidisciplinary nutritional and lifestyle counseling before, during, and after treatment with RDNs, physical activity support, and ongoing behavioral interventions.

This guidance represents the first major multisociety effort to establish evidence-based nutritional protocols to accompany GLP-1 therapy for obesity, and addresses both clinical efficacy and health equity in this expanding area of treatment.

Disclosures can be found the published article.

Source: Obesity Journal