Trying to parse the never-ending deluge of GLP-1 studies can feel like trying to navigate a book-length diner menu. Some are pills, others are injectables, and all promise miraculous weight loss results. Now, new research published in the journal Obesity is cutting through the noise to offer answers on which GLP-1 drug is the most effective for weight loss in non-diabetic patients.  

Pharmacologists from the University of Georgia recently conducted a meta-review of research into three leading GLP-1 medications: semaglutide, liraglutide, and tirzepatide (which you may know better as their brand names Wegovy, Saxenda, and Zepbound, respectively). Because these drugs were originally prescribed for people with diabetes, most long-term studies investigating their efficacy have focused on those individuals. This is the first meta-review to specifically focus on weight loss in patients without diabetes.

After analyzing 15 randomly controlled clinical trials that included more than 14,000 patients, the researchers found a clear winner: Zepbound. Patients taking trispeptide lost over 20 percent of their starting body weight, compared to 15 percent for semaglutide and 8 percent for liraglutide. The rates of patients who experienced side effects for the drugs were comparable across all three, with a slight decline in incidences of diarrhea among liraglutide takers.  

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​​“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,” study author Pooja Gokhale said in a statement. “Tirzepatide seems to be the better option.” 

Why did tirzepatide win out over the others? 

All three drugs bind to GLP-1 receptors. By mimicking the gut hormones, they reduce blood sugar, slow digestion, and curb appetites. But unlike semaglutide and liraglutide, tirzepatide also binds to receptors for another gut hormone, gastric inhibitory polypeptide. It’s this dual action that likely gives it an edge over competitors. 

Of course, just like the ever-proliferating blades from razor companies, pharmaceutical companies are keen to target more and more receptors. Eli Lilly’s retatrutide, currently in trials, binds to the same receptors as trispeptide and adds another receptor to the list. The latest GLP-1 drug was outside the purview of the current study, but preliminary data suggests low doses are comparable to trispeptide with 19 percent body weight loss, but higher doses lead to more side effects.

Even so-called “miracle drugs” have trade-offs.

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