Exploring FDA-approved anti-obesity medications

Clinical guidelines for anti-obesity medications

According to clinical guidelines, anti-obesity medications are indicated for the following individuals:

• Adults. Body mass index (BMI) ≥ 30, or BMI ≥ 27 with weight-related conditions (diabetes, hypertension, high cholesterol).
• Adolescents (12+). BMI at or above the 95th percentile for age and sex.

For individuals of South Asian descent, obesity-related complications develop at a lower BMI. As a result, treatment might begin at a BMI of 27 or greater or 25 if weight-related health conditions are present.

FDA-approved anti-obesity medications

The FDA has approved several medications for chronic weight management, categorized into three primary mechanisms:

1. Intragastrointestinal medications.
2. Centrally acting medications that suppress appetite.
3. Nutrient-stimulated hormone-based medications.

Intragastrointestinal medications

As of January 2025, orlistat (Xenical and Alli) remains the only FDA-approved medication that aids weight loss by inhibiting fat absorption in the gastrointestinal tract. The FDA first approved prescription orlistat, manufactured by Roche under the brand name Xenical, in April 1999 for adults with obesity. The approval of the oral tablet was later expanded to include adolescents aged 12 and older. In 2007, the FDA authorized an over-the-counter (OTC) version of orlistat under the brand name Alli, making it the first weight-loss drug available without a prescription in the U.S.

By reducing dietary fat absorption, orlistat lowers overall calorie intake, contributing to weight loss and potential improvements in waist circumference, systolic blood pressure, and low-density lipoprotein (LDL) cholesterol. Clinical studies have demonstrated an average total body weight reduction of approximately 10%.

Centrally acting medications that suppress appetite

The FDA has approved two oral medications -- phentermine-topiramate and naltrexone-bupropion -- which act on the brain to reduce appetite and food cravings.

Phentermine-topiramate (Qsymia)

Phentermine-topiramate (Qsymia), developed by Vivus, was approved by the FDA in July 2012. This once daily oral tablet is a long-term weight management medication that combines a stimulant (phentermine) and an anticonvulsant (topiramate) to aid in chronic weight management. This helps patients achieve and maintain an 11% reduction in total body weight.

Naltrexone-bupropion (Contrave)

The FDA approved naltrexone-bupropion (Contrave) in September 2014. It is a combination weight-loss medication marketed by Takeda in the U.S. under license from Orexigen Therapeutics. The oral tablet combines an opioid antagonist (naltrexone) and an aminoketone antidepressant (bupropion) to support chronic weight management when used alongside diet, physical activity and behavioral therapy. Clinical studies indicate an average weight loss of 6%.

Nutrient-stimulated hormone-based medications (GLP-1 agonists)

Originally developed for type 2 diabetes, glucagon-like peptide-1 (GLP-1) receptor agonists have become leading treatments for obesity. These medications mimic gut hormones to regulate appetite and food intake, offering substantial weight-loss benefits.

Liraglutide (Saxenda)

In December 2014, the FDA approved liraglutide for chronic weight management in adults and adolescents. The once-daily injection has demonstrated weight-loss benefits but has been largely overtaken by newer, more effective weekly injections.

Semaglutide (Wegovy)

In June 2021, the FDA approved Wegovy, manufactured by Novo Nordisk, for chronic weight management in adults with obesity or overweight. This once-weekly injection of semaglutide is linked to weight loss ranging from 8% to 21% of total body weight, making it one of the most effective obesity treatments available.

Tirzepatide (Zepbound)

In November 2023, the FDA approved Zepbound for chronic weight management, followed by an expanded indication in December 2024 for moderate-to-severe obstructive sleep apnea. Developed by Eli Lilly, this once-weekly injection targets both GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) receptors, potentially offering greater efficacy than semaglutide.

Clinical data underscores Zepbound's effectiveness, with patients experiencing an average 20.2% weight loss over 72 weeks, compared to 13.7% with Wegovy, translating to a 47% greater relative weight reduction.

Barriers to access and affordability

Despite the effectiveness of these treatments, insurance coverage remains a major barrier. Medicare does not cover anti-obesity medications unless prescribed for patients with cardiovascular disease or diabetes. Medicaid coverage varies by state, with only 14 state Medicaid programs covering GLP-1 drugs for obesity. Many private insurance plans exclude obesity treatments, leaving patients to pay out of pocket for medications that can cost between $900 and $1,400 per month.

Emerging trends

Pharmaceutical companies are investing in next-generation obesity therapies, focusing on improving efficacy, extending dosing intervals and minimizing side effects. Combination therapies targeting multiple metabolic pathways are also under development, potentially revolutionizing weight management.

On the policy front, advocacy groups and legislators are pushing for expanded insurance coverage. The Treat and Reduce Obesity Act, for instance, aims to include anti-obesity medications under Medicare Part D, which could significantly improve access for older adults.

As obesity rates continue to rise, the pharmaceutical industry is driving a critical shift in treatment from lifestyle modifications alone to evidence-based pharmacotherapy. With advancements in drug development and growing clinical evidence, GLP-1 medications help patients better manage obesity. However, achieving widespread access will require a concerted effort to address affordability and coverage barriers.

Alivia Kaylor is a scientist and the senior site editor of Pharma Life Sciences.