FDA prioritizes fat loss over muscle loss in new obesity drug guidelines

USA – As competition heats up in the obesity treatment market, the U.S. Food and Drug Administration (FDA) has released draft guidance aimed at establishing study standards that prioritize fat loss over general weight loss, which may also involve muscle mass reduction.

This comes as numerous clinical obesity programs are expected to release results in 2025, adding to the already intense rivalry among pharmaceutical companies, including market leaders Eli Lilly and Novo Nordisk, and their emerging competitors.

The FDA’s guidelines stipulate that a weight-loss drug for obesity or overweight patients with related health conditions is considered effective if, after one year on the maintenance dose, it achieves a statistically significant average weight reduction of at least 5% compared to a control group.

For safety evaluations, the agency recommends trials involving at least 3,000 randomized participants to the drug within its proposed dosage range and at least 1,500 participants assigned to a placebo, all followed for at least one year.

Shifting the focus to fat loss

A major highlight of the draft guidance addresses the need for body composition assessments. Historically, 60–90% of weight reduction in drug trials has been attributed to fat mass loss, while accompanying lean muscle mass loss has largely been overlooked.

However, the FDA now emphasizes the importance of ensuring that weight loss induced by drugs or biologics is primarily due to fat reduction rather than muscle loss.

To achieve this, the FDA recommends that a representative sample of trial participants undergo body composition evaluations using Dual-Energy X-ray Absorptiometry (DXA) or similar technologies at baseline and follow-up stages.

For companies seeking to claim efficacy based on changes in body composition, the FDA advises early consultation to align with the targeted clinical condition.

In addition, the FDA underscores the need for diverse patient populations in clinical trials. This includes individuals with severe obesity and those with weight-related comorbidities such as type 2 diabetes or hypertension.

It also calls for the inclusion of patients from racial and ethnic groups with higher obesity prevalence, ensuring that study results reflect a wide range of populations.

Key clinical readouts expected

Several highly anticipated Phase III trial results are set to emerge in 2025. Among them is Eli Lilly’s oral GLP-1 agonist, orforglipron, with data expected by mid-year.

Analysts predict the drug could generate up to US $10 billion in annual sales by the end of the decade.

Lilly is also slated to release cardiovascular outcomes data for its GIP/GLP-1 agonist tirzepatide, marketed as Zepbound for weight loss, through its Phase III SURPASS CVOT study.

Positive results from this trial could improve insurance coverage for the drug, further expanding its market reach.

Broader implications for the industry and consumers

The FDA’s updated guidance has significant implications for both the pharmaceutical industry and consumers.

For manufacturers, the requirement to focus on fat loss over general weight reduction adds a layer of complexity, necessitating more rigorous research and longer clinical trials.

While this may increase development costs and timelines, it is also likely to drive innovation, pushing companies to develop more effective treatments that meet these higher standards.

On the consumer side, these changes ensure that weight-loss drugs will be held to stricter efficacy benchmarks, providing individuals with access to medications that have demonstrated meaningful results.