HMN 2026: How Tirzepatide GLP-1 medication may be most effective for weight loss

GLP-1 medications are marketed to help you lose weight, but one may be better at it than the rest, according to a new meta-analysis from the University of Georgia.

Tirzepatide, better known as Zepbound for weight loss and Mounjaro for treatment of type 2 diabetes, helped patients lose more than 20% of their starting body weight across the reviewed studies.

Semaglutide (marketed under the brand name Wegovy) and liraglutide (Saxenda) did lead to weight loss, but it was significantly less, at 15% and 8%, respectively.

The review is the first to compare the efficacy of the three FDA-approved GLP-1 medications in nondiabetic patients using the drugs for weight loss.

“We were interested in finding which drug gives the most weight loss and doesn’t have higher rates of side effects like nausea and gastrointestinal problems. Tirzepatide seems to be the better option,” said Pooja Gokhale, corresponding author of the review and a doctoral student in the UGA College of Pharmacy.

Tirzepatide’s dual mechanism of action may help maximize weight loss

Chances are someone you know is taking a GLP-1 medication.

Short for glucagon-like peptide-1, GLP-1s are highly effective FDA-approved medications that treat type 2 diabetes. Increasingly, they’re being used by more people to lose weight.

About 1 in 8 Americans is currently taking a GLP-1, according to a recent poll from KFF, formerly known as the Kaiser Family Foundation. And 1 in 5 have taken the medication in the past.

“Some people call these ‘miracle drugs’ because the weight loss effect is real,” said Lorenzo Villa-Zapata, co-author of the paper and an assistant professor in the UGA College of Pharmacy. “But what some people don’t understand is that when they stop taking the medication, they may gain all that weight back.” (The current study did not evaluate weight gain after the discontinuation of GLP-1 medications.)

GLP-1 medications act as a pharmaceutical version of a natural hormone in the gut, lowering blood sugar, keeping people feeling fuller longer and slowing digestion.

But while brand names like Wegovy and Saxenda are solely focused on mimicking GLP-1 receptors, tirzepatide targets both GLP-1 receptors and another gut hormone known as GIP.

That may make all the difference for people looking to maximize weight loss, the researchers said.

Liraglutide least effective

The researchers analyzed the results of 15 randomized controlled phase 3 clinical trials, comprising more than 14,000 patients.

Participants saw the largest weight reduction when prescribed the maximum dose of tirzepatide (between 10 and 15 milligrams).

Liraglutide proved the least effective of the three drugs. It also requires daily injections, compared with the weekly dosing schedule of tirzepatide and semaglutide medications.

At the time of the review, the FDA had not yet approved the Wegovy pill, an oral version of the GLP-1 medication that is now available in 25 mg pills.

However, the researchers did a sensitivity analysis of a 50 mg version and found that it was not as effective as tirzepatide in nondiabetic patients looking to lose weight. It was “almost as good as the injectable semaglutide,” though, Gokhale said.

Published by Obesity, the analysis originated as part of the College of Pharmacy’s systematic reviews and meta-analysis course. Doctor of Pharmacy candidate Michael Lim was first author of the publication, and Akwasi Akosah, a doctoral candidate in UGA’s pharmaceutical health services outcomes and policy program, co-authored the paper.

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