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Although decreasing food intake and increasing exercise can help people with obesity lose weight, it often isn’t enough to help them keep the weight off long-term. Drugs may be the answer for maintaining weight loss and minimizing the risk for complications such as type II diabetes and cardiovascular disease.

Now, scientists are developing a slew of anti-obesity drugs not only targeting the gut, but the brain. These drugs target enzymes that process fats in the gut to increase metabolic rates. They also modulate the levels of hormones in the brain such as dopamine and epinephrine to curb hunger and cravings. The most recently approved drug to hit the scene, WeGovy, looks and acts like a hormone that regulates levels of insulin and appetite through it’s effects on the brain and the gut.

Central nervous system (CNS) stimulants

CNS stimulants increase chemicals in the brain such as epinephrine to suppress appetite. Stimulants are only approved for short-term use in people with obesity (1).

FDA approved CNS stimulant anti-obesity drugs:

• Phentermine (Lomaira and Adipex-P)
• Diethylpropion (Tenuate and Tepanil)
• Phendimetrazine (Bontril)
• Benzphetamine (Didrex and Recede)

Phentermine can be combined with topiramate, a drug commonly used to treat seizures and migraines, to reduce negative side effects such as dry mouth. These drugs are combined in an extended-release pill dubbed Qsymia which is approved for long-term use. Exactly how topiramate promotes weight loss is unknown (1).

Neurological Agents

Bupropion/Naltrexone (Contrave and Mysimba) is an FDA-approved anti-obesity drug that suppresses hunger (1).

Bupropion increases the amount of dopamine and norepinephrine in the brain.

1. Speeds up metabolism
2. Reduces hunger and cravings
3. Also prescribed for smoking cessation and depression

Naltrexone blocks opioid receptors.

1. Inhibits endorphins, an opioid that increases hunger
2. Also prescribed for opioid and alcohol addiction

Gastrointestinal Agents

Orlistat prevents the absorption of fats by inhibiting lipases in the stomach, small intestine, and pancreas. Patients can acquire orlistat via a prescription (Xenical) or over the counter in a lower dose (Alli).

Glucagon-like Peptide-1 (GLP-1) Receptor Agonists (GLP1-RAs)

Produced by cells in the intestine, GLP-1 is a 30 amino acid hormone that regulates a variety of processes involved in diabetes and obesity including insulin secretion and hunger via its effects on the gut and the brain (2).

The GLP1-RAs, liraglutide and semaglutide, are greater than 90% similar to GLP-1. Several clinical studies have shown that both GLP1-RA drugs help sustain long-term weight loss (3-4).

Liraglutide is FDA approved for long-term use in adults and adolescents with obesity and requires a weekly injection (3-4). A monthly injection of semaglutide (Wegovy) was approved in 2021 for adults with obesity (5).

Check out this profile on Fatima Stanford, obesity medicine clinician, and her compassionate view on obesity.

References

1. Won Son, J. and Kim, S. Comprehensive Review of Current and Upcoming Anti-Obesity Drugs. Diabetes Metab J 44, 802-818 (2020).
2. Knudsen, L.B. and Lau, J. The Discovery and Development of Liraglutide and Semaglutide. Front Endocrinol 10, 1664-2392 (2019).
3. Pi-Sunyer, X., et al. A Randomized, Controlled Trial of 3.0 mg of Liraglutide in Weight Management. N Engl J Med 373, 11-22 (2015).
4. Kelly, S.A. et al. A Randomized, Controlled Trial of Liraglutide for Adolescents with Obesity. N Engl J Med 382, 2117-2128 (2020).
5. Wilding, J.P.H, et al. Once-Weekly Semaglutide in Adults with Overweight or Obesity N Engl J Med 383, 989-1002 (2021).