Weight Loss Pills, Past and Present
Health ConditionsWeight ManagementWeight Loss

Weight Loss Pills, Past and Present: How They Work, Safety, and More

Can prescription drugs help you lose weight? Here’s what to know.
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Updated on January 15, 2025
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The U.S. Food and Drug Administration has had to pull several weight loss drugs from the market because of safety concerns.Aurelija Diliute/Shutterstock
The need for obesity treatments is urgent — more than two-thirds of U.S. adults are overweight, and more than 40 percent have obesity.

 Obesity is a leading cause of preventable premature deaths as well as health problems like heart disease, stroke, type 2 diabetes, and certain cancers.
Roughly half of U.S. adults try to lose weight, most often by exercising more, eating less, and adding more fruits and vegetables to their diets.

 Many people can lose weight with those approaches, but multiple factors in addition to lifestyle changes play a part in managing obesity.

“[Obesity] is a lifelong disease that requires lifelong intervention, and even when people make lifestyle changes, they still have to fight against weight gain,” says Timothy Garvey, MD, a professor in the department of nutrition sciences and the director of the Diabetes Research Center at the University of Alabama in Birmingham. “Medications can stop the processes that cause this weight gain.”

Early Weight Loss Drugs

The weight loss medications on the market today are generally approved for adults with obesity who have a body mass index (BMI) of 30 or higher, or adults with a BMI of 27 or greater who have at least one weight-related health problem such as high blood pressure, type 2 diabetes, or high cholesterol.

But until recently, very few patients who met those criteria took drugs to lose weight. One study collected prescription data from more than 2.2 million adults eligible for treatment with weight loss medications from 2009 to 2015.
Part of the problem came down to safety concerns, particularly because so many of the first drugs used for weight loss decades ago had potentially life-threatening side effects.

As far back as the 1940s, cocktails of appetite suppressants known as “rainbow pills” were heavily marketed to American women.

 The brightly colored capsules often contained amphetamines, diuretics, laxatives, and thyroid hormones to maximize weight loss. They were typically mixed with drugs like benzodiazepines, barbiturates, and antidepressants. By the 1960s, after those potent cocktails of drugs had caused dozens of deaths, the U.S. Food and Drug Administration (FDA) removed them from the market.

“None of these medications were tested in long-term trials prior to repurposing them for the treatment of obesity. This raises the risk that they will have side effects not recognized in short-term therapy,” says Frank Greenway, MD, the chief medical officer and a professor at the Pennington Biomedical Research Center at Louisiana State University in Baton Rouge.

In the 1990s, another untested weight loss cocktail nicknamed fen-phen started taking off.

 This cocktail mixed the psychiatric drug fenfluramine, which boosts levels of the brain chemical serotonin and induces feelings of satiety, with the appetite suppressant phentermine. An older version of fenfluramine, marketed as Pondimin, was on the market for more than two decades, and a newer version called dexfenfluramine, marketed as Redux, was sold for about a year, before both were recalled in 1997 because of concerns that the products caused heart valve defects.
An appetite suppressant called sibutramine, marketed as Meridia, was recalled by the FDA in 2010 after more than a decade on the market, because of an increased risk of cardiovascular events and strokes.

 Next up, the prescription weight loss drug lorcaserin (Belviq) was recalled by the FDA over cancer concerns in 2020, after more than a decade on the market.

Tougher Drug Testing Requirements

After so many weight loss drugs were recalled because of dangerous side effects, in the late 1990s the FDA recommended that new medications to treat obesity undergo yearlong clinical trials before approval.

All the medications approved in the last decade have a good track record of safety so far, says Adam Gilden, MD, an associate professor and obesity researcher at the University of Colorado School of Medicine in Aurora. These newer drugs either combine medicines that have good safety records when used individually or those that have been used for a long time to manage type 2 diabetes before gaining traction as obesity treatments.

“So, we can feel good that these medicines are safe,” Dr. Gilden says. “Also, every one of these medicines will be subjected to large post-marketing trials, which will further assess safety and longer-term efficacy.”

“I think it is a very exciting time for obesity medicine because we now have several effective treatments to choose from,” says Melanie Jay, MD, an obesity researcher and an associate professor at the New York University Grossman School of Medicine in New York City.

Weight Loss Drug Options

For many patients today, a decision about which weight loss medication to try may come down to several factors, including what other medications they take, which drugs are covered by insurance or are most affordable, and whether people prefer pills or injected medicines, Dr. Jay says.

“I advise people to speak to their physician to choose an initial medication and see how they respond,” Jay says. “It’s not uncommon to switch medications or have to add a second or third medication.”

Weight loss medications should not be used during pregnancy or conception.

 Those with kidney impairment and those at risk for kidney stones should discuss the risks and benefits of weight loss medication with a medical provider.

 So should those who have an eating disorder or are at risk.

 Though it can sometimes be expensive or difficult to access support with lifestyle interventions, the most recent guidelines on treating obesity state that those taking weight loss medications should do their best to combine them with lifestyle changes.

 This preferably includes intensive and comprehensive lifestyle interventions including diet, exercise, and behavioral counseling in which the patient or client is seen one to two times a week for several weeks to a year.

Here’s what you need to know about the prescription weight loss drugs that are currently approved.

  • Tirzepatide (Zepbound) This weekly injected medicine was approved by the FDA in 2023 to treat adults with obesity and overweight adults with at least one weight-related chronic health problem.

     Tirzepatide mimics two hormones that regulate insulin secretion and digestion: glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). It is widely believed to be the most potent weight loss drug ever approved for sale: In the SURMOUNT-1 trial, participants using the highest dose lost an average of 22.5 percent of their body weight.

     Common side effects include nausea, diarrhea, vomiting, and constipation; rare but potentially dangerous reactions include severe gastrointestinal disease and acute injury to the pancreas, kidneys, or gallbladder.
  • Semaglutide (Wegovy) This weekly injected medicine was approved by the FDA in 2021 to treat adults with obesity and overweight adults with at least one weight-related chronic health problem.

     It’s another GLP-1 receptor agonist that mimics a hormone in the brain that regulates appetite. Common side effects include nausea, diarrhea, vomiting, constipation, stomach pain, headache, and fatigue. It can’t be used in combination with liraglutide or other GLP-1 receptor agonists that are prescribed for type 2 diabetes. Like other drugs in this family of medicines, including tirzepatide and liraglutide, it carries an increased risk of pancreatitis and has been linked to thyroid tumors in animals.
  • Naltrexone-Bupropion (Contrave) This oral drug was approved by the FDA in 2014.

     It’s a combination of two drugs that are used to treat addiction and depression, and it suppresses appetite and makes people feel full sooner. Common side effects include constipation, dizziness, diarrhea, dry mouth, headache, increased blood pressure, elevated heart rate, insomnia, liver damage, nausea, and vomiting. It shouldn’t be used by people with uncontrolled blood pressure, seizures, a history of anorexia or bulimia, people taking psychiatric drugs containing bupropion (Wellbutrin, Zyban), or individuals dependent on opioids or in withdrawal from drugs or alcohol. It can increase suicidal thoughts or actions.
  • Liraglutide (Saxenda) This daily injected drug was approved by the FDA in 2014 for adults and in 2020 for children ages 12 and older with obesity.

     It’s in a family of medicines known as glucagon-like peptide-1 (GLP-1) receptor agonists, which work by mimicking a hormone in the brain that regulates appetite and food consumption. Common side effects include nausea, diarrhea, constipation, abdominal pain, headache, and increased heart rate. Rare side effects include an increased risk of pancreatitis, and it’s been linked to thyroid tumors in animals. In a smaller dose, liraglutide is used as a diabetes medication called Victoza, which should not be used in conjunction with Saxenda.
  • Phentermine-Topiramate (Qsymia) This pill was approved by the FDA in 2012 for adults who are overweight or obese, and in 2022 for patients ages 12 and older with obesity.

     This combination pill works to suppress appetite and make people feel full sooner. Common side effects include constipation, dizziness, dry mouth, tingling in hands and feet, brain fog or cognitive impairment, and difficulty sleeping. It shouldn’t be used by people with glaucoma or hyperthyroidism, by women who are pregnant or breastfeeding, or by some individuals with a history of heart attack, stroke, heart rhythm disorders, kidney disease, or mood problems.
  • Orlistat (Xenical, Alli) This pill was approved by the FDA in 1999 as a prescription weight loss drug (Xenical) and in 2007 at a lower dose for nonprescription use (Alli).

     It works in the gut to limit the amount of fat absorbed from foods you eat. Common side effects include diarrhea, gas, stomach pain, and leakage of oily stools. It’s also linked to rare cases of severe liver injury; dangerous interactions with cyclosporine, a drug to prevent organ transplant rejections; and the potential for malnutrition if patients don’t take a multivitamin.

     Orlistat has been shown to decrease absorption of fat-soluble vitamins as well as some prescription medications, including Amiodarone, which is used to treat irregular heartbeats, and ciclosporin, which is used to treat inflammatory diseases like rheumatoid arthritis. Orlistat may also affect the dosage of warfarin, an anticoagulant.

The Takeaway 

  • For many people with obesity who struggle to shed excess pounds, prescription weight loss drugs can help when lifestyle changes like calorie restriction and exercise aren’t enough.
  • So far, drugs approved within the past decade have proved safer than earlier weight loss drugs.
  • Before you start weight loss medication, discuss your options with a healthcare provider to learn the potential risks and side effects.

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Deepa Sannidhi, MD

Medical Reviewer

Deepa Sannidhi, MD, is board-certified in family medicine, obesity medicine, and lifestyle medicine. She is an associate clinical professor in the department of family medicine at UC San Diego and serves as assistant program director for the UCSD-SDSU general preventive medicine residency. She serves as a concentration lead for the UCSD Herbert Wertheim School of Public Health. She teaches students and trainees at all levels of training.

Clinically, she partners with the UCSD Center for Integrative Medicine and Center for Advanced Weight management to offer the UCSD Supervised Lifestyle and Integrative Medicine (SLIM) program, which is an innovative medical weight loss program integrating lifestyle and integrative medicine approaches with medical weight loss using anti-obesity medications in a shared medical appointment setting. 

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Lisa Rapaport

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Lisa Rapaport is a journalist with more than 20 years of experience on the health beat as a writer and editor. She holds a master’s degree from the UC Berkeley Graduate School of Journalism and spent a year as a Knight-Wallace journalism fellow at the University of Michigan. Her work has appeared in dozens of local and national media outlets, including Reuters, Bloomberg, WNYC, The Washington Post, Los Angeles Times, Scientific American, San Jose Mercury News, Oakland Tribune, Huffington Post, Yahoo! News, The Sacramento Bee, and The Buffalo News.
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Resources
  1. Obesity and Overweight. Centers for Disease Control and Prevention. October 25, 2024.
  2. Martin C et al. Attempts to Lose Weight Among Adults in the United States, 2013–2016. Centers for Disease Control and Prevention. July 2018.
  3. Masood B et al. Causes of obesity: A review. Clinical Medicine. July 2023.
  4. Prescription Medications to Treat Overweight & Obesity. National Institute of Diabetes and Digestive and Kidney Diseases. June 2024.
  5. Saxon DR et al. Anti-Obesity Medication Use in 2.2 Million Adults Across 8 Large Healthcare Organizations: 2009–2015. Obesity. October 11, 2019.
  6. Ingelfinger JR et al. STEP 1 for Effective Weight Control — Another First Step? New England Journal of Medicine. March 18, 2021.
  7. Cohen PA et al. The Return of Rainbow Diet Pills. American Journal of Public Health. September 2012.
  8. Wellman PJ et al. Synergistic interactions between fenfluramine and phentermine. American Journal of Public Health. July 1999.
  9. FDA Drug Safety Communication: FDA Recommends Against the Continued Use of Meridia (sibutramine). U.S. Food and Drug Administration. February 6, 2018.
  10. FDA requests the withdrawal of the weight-loss drug Belviq, Belviq XR (lorcaserin) from the market. U.S. Food and Drug Administration. January 14, 2022.
  11. Colman E. Food and Drug Administration's Obesity Drug Guidance Document: A Short History. American Heart Association Journals. May 2012.
  12. Munoz-Mantilla D. Top Weight Loss Medications. Obesity Medicine Association. January 26, 2024.
  13. Poore W et al. Obesity and Its Impact on Kidney Stone Formation. Reviews in Urology. 2020.
  14. Chiappini S et al. Is There a Risk for Semaglutide Misuse? Focus on the Food and Drug Administration’s FDA Adverse Events Reporting System (FAERS) Pharmacovigilance Dataset. Reviews in Urology. July 11, 2023.
  15. Golovaty I et al. Lifestyle Intervention Requirements for Novel Antiobesity Medications — Necessary Adjunct or Harmful Gatekeeper? JAMA Internal Medicine. November 25, 2024.
  16. Jensen MD et al. 2013 AHA/ACC/TOS Guideline for the Management of Overweight and Obesity in Adults: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and The Obesity Society. Circulation. June 24, 2014.
  17. FDA Approves New Medication for Chronic Weight Management. U.S. Food and Drug Administration. November 8, 2023.
  18. Jastreboff AM et al. Tirzepatide Once Weekly for the Treatment of Obesity. New England Journal of Medicine. July 21, 2022.
  19. FDA Approves New Drug Treatment for Chronic Weight Management, First Since 2014. U.S. Food and Drug Administration. June 4, 2021.
  20. CENTER FOR DRUG EVALUATION AND RESEARCH Approval Package for APPLICATION NUMBER:200063Orig1s000. U.S. Food and Drug Administration. September 10, 2014.
  21. SAXENDA (liraglutide [rDNA origin] injection). U.S. Food and Drug Administration.
  22. FDA approves weight management drug for patients aged 12 and older. U.S. Food and Drug Administration. June 15, 2021.
  23. FDA approves treatment for chronic weight management in pediatric patients aged 12 years and older. U.S. Food and Drug Administration. June 27, 2022.
  24. Orlistat (marketed as Alli and Xenical) Information. U.S. Food and Drug Administration. July 8, 2015.
  25. Prescription Medications to Treat Overweight & Obesity.  National Institute of Diabetes and Digestive and Kidney Diseases. June 2024.