How Weight Loss Pills Have Changed — and What That Means for Safety

“[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.”

“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.

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 a professor at the New York University Grossman School of Medicine in New York City.

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.”

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

Tirzepatide (Zepbound)

Common side effects: Nausea, diarrhea, vomiting, and constipation.

Interactions and risks: Rare but potentially dangerous reactions include severe gastrointestinal disease and acute injury to the pancreas, kidneys, or gallbladder.

Semaglutide (Wegovy)

How it works: It’s another GLP-1 receptor agonist that mimics a hormone in the brain that regulates appetite.

Common side effects: Nausea, diarrhea, vomiting, constipation, stomach pain, headache, and fatigue.

Interactions and risks: 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)

How it works: 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: Constipation, dizziness, diarrhea, dry mouth, headache, increased blood pressure, elevated heart rate, insomnia, liver damage, nausea, and vomiting.

Interactions and risks: 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)

How it works: 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: 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.

Interactions and risks: 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)

How it works: This combination pill suppresses appetite and makes people feel full sooner.

Common side effects: Constipation, dizziness, dry mouth, tingling in hands and feet, brain fog or cognitive impairment, and difficulty sleeping.

Interactions and risks: 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)

How it works: It works in the gut to limit the amount of fat absorbed from foods you eat.

Common side effects: Diarrhea, gas, stomach pain, and oily stool leakage.

• 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 starting weight loss medication, discuss your options with a healthcare provider to learn about potential risks and side effects.