Three GLP-1 drugs are best at helping obese and overweight people drop weight, including one that hasn’t yet been approved for that purpose.

A new evidence review published in the Annals of Internal Medicine shows that the widely-known drugs tirzepatide (Zepbound) and semaglutide (Wegovy) are both safe and effective at helping the obese shed pounds.

However, a third drug also FDA-approved for weight loss, liraglutide (Saxenda), didn’t work as well as the others, researchers found after reviewing data from dozens of clinical trials.

The review also found that a GLP-1 drug still in development, called retatrutide, might be more effective than either Zepbound or Wegovy.

“We found that, of the 12 GLP-1 (drugs) identified by our search, the greatest mean body weight reduction was reported in randomized controlled trials of retatrutide, tirzepatide, and semaglutide,” concluded the research team led by Dr. Mark Eisenberg, a professor of medicine at McGill University in Montreal, Canada.

GLP-1 drugs, initially developed to treat diabetes, help people lose weight by slowing digestion in the stomach and sending signals to the brain indicating that a person has eaten enough and feels full.

The drugs mimic a hormone secreted by the small intestine when people eat food.

For the new evidence review, researchers analyzed data from 26 previous clinical trials of the drugs, involving nearly 15,500 participants.

Compared to placebo, the data showed that:

• Tirzepatide resulted in weight loss of nearly 18% after 72 weeks.

• Semaglutide produced nearly 14% weight loss after 68 weeks.

• Retatrutide generated weight loss of more than 22% after 48 weeks.

Each of those drugs are taken once a week, by an injection.

By comparison, the FDA-approved drug liraglutide only resulted in just under 6% weight loss after 26 weeks, the researchers found.

Common adverse side effects from the drugs included nausea, vomiting, diarrhea and constipation, researchers noted. However, side effects so bad people had to stop taking the drugs were rare.

Retatrutide is currently being developed by Eli Lilly & Co., and is being tested in ongoing clinical trials.

Researchers noted that one downside of the drugs is that people have to keep taking them, lest they regain weight.

“In our systematic review, (clinical trials) with longer treatment durations demonstrate similar weight loss results to those with shorter follow-up, reinforcing the idea that continuous treatment may be required,” the team wrote.