Developing Drugs and Biologics for Weight Reduction – Examining FDA’s New Guidance

Since 1990, the prevalence of obesity has more than doubled and is now considered to be a global epidemic.¹ In response, the drug market has seen a recent surge in the popularity of new weight reduction drugs including blockbusters such as Wegovy and Zepbound. The explosive growth of the anti-obesity market is expected to continue for at least the next decade,² and so the number of new weight reduction drugs under development will also continue to grow.

In line with the increased development of new weight reduction drugs, the Food and Drug Administration (FDA) released an update to its previous draft guidance for industry “Developing Products for Weight Management,” released in 2007. The 2025 draft guidance for industry, “Obesity and Overweight: Developing Drugs and Biological Products for Weight Reduction,” uses the same framework as the previous guidance, but with additional recommendations based on newly identified risks and the findings from recently completed clinical studies of weight reduction drugs.

Body Mass Index (BMI)

In the new guidance, FDA again recognizes the importance of Body Mass Index (BMI) in identifying both pediatric and adult patients who are either obese or overweight. While FDA acknowledges its limitations, it still considers BMI to be “inexpensive, easy to calculate, reproducible, and correlates strongly with total body fat in nonelderly adults.”

Furthermore, FDA still considers baseline adjusted, mean percentage change in BMI to be an effective method to assess a change in adiposity in obese or overweight individuals. However, as BMI does not inform the distribution of excess body fat, FDA states that it can be supplemented (but not replaced) in certain individuals with other anthropometric measures such as waist circumference.

For all adults, obesity should be classified by BMI in accordance with the guidelines established by the World Health Organization (WHO) and the National Institutes of Health (NIH), ³ Pediatric obesity should be classified by BMI in accordance with US Center for Disease Control and Prevention (CDC) growth charts,⁴ which include additional stratifications for age and sex.

Clinical Assessments of Weight Reduction

Overall, FDA’s recommendations for clinical trial designs are consistent with those provided in the 2007 guidance. In general, early phase studies should evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of new weight reduction therapeutics, across a range of doses and BMIs, to account for the potential effects of excess adiposity. Phase 3 studies should be randomized, double-blind, and placebo-controlled with mean percentage change in body weight, instead of a control, as the primary efficacy endpoint. In all studies, participants should be overweight or obese individuals with BMIs ≥30 kg/m² or ≥27 kg/m² if accompanied by at least one comorbidity.

The efficacy benchmark for weight reduction drugs remains unchanged from the 2007 guidance: the percentage weight reduction between the investigational drug and control should be at least 5% and statistically significant. Importantly, the new guidance cautions against the use of the “responder analyses” that were secondary endpoints in many of the clinical studies for recently approved weight reduction drugs such as Wegovy (i.e., the proportion of subjects achieving ≥5%, 10%, or 15% weight reduction), as they may exaggerate treatment effects.

The recommended safety database size remains unchanged from the previous guidance (3,000 investigational drug/1,500 placebo for ≥1 year at the maintenance dosage).

In Halloran’s experience, the FDA has been very unwilling to deviate from these core recommendations, and so sponsors will likely need significant justification to do so.

Pediatrics

A key update from the previous guidance is the recommendation that pediatric studies include younger subjects (aged 6 years and older); the previous guidance limited initial pediatric studies to adolescents only (aged 12 years and older). The new guidance also recommends separate trials or cohorts for adolescents and younger subjects. Based on Halloran’s own experiences, and the precedent set by previously approved products, FDA is generally in agreement with delaying pediatric studies of weight reduction drugs until after product approval. However, that could change as the childhood obesity epidemic worsens and increasing numbers of weight reduction drugs are demonstrated to be safe and effective in children.

Patients with Type 2 Diabetes

FDA’s viewpoint on additional indications for the delay or prevention of Type 2 Diabetes has evolved since the previous guidance. In the previous guidance, FDA stated that a stand-alone indication for Type 2 Diabetes would require evidence of effectiveness through a mechanism that is independent of weight reduction. The current guidance takes this a step further by stating that sponsors will also be required to demonstrate evidence of clinical benefit to receive the stand-alone indication. This is an important difference as FDA has never approved a drug for the prevention or to delay the onset of Type 2 Diabetes and so sponsors seeking such an indication will not be able to rely on precedent when designing future studies.

Suicide Risk Assessment

The reported association of weight reduction drugs and an increased risk of depression or suicide led to the rejection or removal of several weight reduction drugs from US and European markets.⁵ FDA also received reports of suicidal ideation associated with semaglutide, although the reports have yet to be verified, and no direct link has been established. FDA clearly considers the risk to be worthy of consideration as latest guidance recommends that sponsors include an assessment of suicide risk in the development plans for all centrally acting weight reduction drugs; suicide risk was not mentioned in the 2007 guidance.

In summary, the 2025 FDA guidance for sponsors developing drugs or biological products for weight reduction keeps most of the core recommendations from the 2007 guidance, but with additional specificities based on newly identified risks and the results of recently completed clinical trials. The release of this guidance appears to be in response to the recent boom in the weight-reduction drug market that is expected to continue through the next decade.

If you are developing a weight reduction product, and/or have questions about the impact of this guidance, contact our team.

References

1. WHO. Obesity and overweight [Internet]. 2025 [cited 2025 May 30]. Available from: https://www.who.int/news-room/fact-sheets/detail/obesity-and-overweight
2. Research and Markets. GlobeNewswire News Room. 2025 [cited 2025 May 30]. Anti-Obesity Drugs Market Industry Trends, Sales Forecast, Key Players and Global Forecasts to 2035: Semaglutide & Tirzepatide Lead the Global Anti-Obesity Drug Market Boom. Available from: https://www.globenewswire.com/news-release/2025/03/17/3043491/28124/en/Anti-Obesity-Drugs-Market-Industry-Trends-Sales-Forecast-Key-Players-and-Global-Forecasts-to-2035-Semaglutide-Tirzepatide-Lead-the-Global-Anti-Obesity-Drug-Market-Boom.html
3. NIH. Clinical Guidelines on the Identification, Evaluation, and Treatment of Overweight and Obesity in Adults. National Heart, Lung, and Blood Institute; 1998.
4. CDC. 2000 CDC growth charts for the United States: methods and development. Vital Health Stat. 2002;11:1.
5. Wang W, Volkow ND, Berger NA, Davis PB, Kaelber DC, Xu R. Association of semaglutide with risk of suicidal ideation in a real-world cohort. Nat Med. 2024 Jan;30(1):168–76.