Should You Try Medication to Lose Weight?

Edward Abramson, PhD

If you're thinking about Ozempic, Wegovy (semaglutide), or Mounjaro and newly approved Zepbound (tirzepatide), it's easy to overlook older medications and programs to treat obesity.

In addition to semaglutide and tirzepatide, four older medications are approved by the Food and Drug Administration (FDA) for weight loss. Although they don't produce as much weight loss, you might consider them since they're less expensive and don't require weekly injections.

I'll briefly describe all of the medications and the average weight loss they produce. I'll compare the results to behavioral programs like Weight Watchers and Noom.

The medication that produces the most weight loss is Zepbound. One study found that after 72 weeks, the average weight loss was 21 percent of body weight. That approaches the results from bariatric surgeries, which typically result in 25 to 30 percent weight loss after one year. Wegovy is almost as effective as Zepbound, with a 14.9 percent weight loss at 68 weeks. I've discussed some of the pros and cons of these medications in an earlier post.

Older medications that are administered orally may produce significant but less dramatic weight loss.¹

• Qsymia is a combination of phentermine, an appetite suppressant, and topiramate, an antiepileptic that reduces appetite. A 56-week follow-up found a 10.9 percent weight loss.
• Contrave, a combination of naltrexone, an opiate antagonist, and bupropion, an antidepressant, was found to produce a 6 percent weight loss after 56 weeks.
• Xenical (orlistat) decreases the absorption of fats but frequently has negative gastrointestinal effects (flatulence, diarrhea). The mean weight loss is between 2.8 to 4.8 percent of body weight. Alli is an over-the-counter medication that is a lower dose of orlistat.
• Phentermine (Adipex-P, Lomaira) is a stimulant that suppresses appetite. It's FDA-approved for short-term (12 weeks) use. It is the least expensive and most widely used anti-obesity medication. Despite the FDA caution, phentermine is often prescribed for more than 12 weeks. It shouldn't be used by patients with a history of hypertension, glaucoma, heart disease, or substance abuse. After 28 weeks, the average weight loss is 4.4 percent of body weight.

Compared to these medications, a typical behavioral intervention lasting six months, which includes self-monitoring, dietary counseling, and physical activity recommendations, typically results in a 5 to 10 percent weight loss. For example, Weight Watchers participants average 5.9 percent weight loss after 12 months. Noom, an online behavioral lifestyle intervention program, averages a 5.2 percent weight loss.

Keep in mind that for all medications, surgeries, and behavioral or online programs, you'll probably regain some weight after going off the medication or program. Unfortunately, there's no long-term magic, but increasing physical activity can help minimize regaining weight.