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June 11, 2022 - Tirzepatide (Mounjaro®) is a new diabetes drug from Lilly that is a first-in-class dual GLP-1/GIP receptor agonist. GLP-1 and GIP are hormones secreted by the small intestine, whose actions include stimulating insulin release and suppressing hunger. GLP-1 receptor agonists have been available since 2005, and tirzepatide is the first drug to target both GLP-1 and GIP receptors (see GLP-1 and GIP illustration). In trials, tirzepatide has had some eye-opening effects on blood sugars and weight loss. Highlights from these studies are reviewed below.

A trial (N=1879) that compared three doses of tirzepatide (5 mg, 10 mg, 15 mg) to semaglutide 1mg (Ozempic®) in diabetics who were uncontrolled on metformin (average baseline A1C 8.28%) found that tirzepatide lowered the average A1C by 2 - 2.3% over 40 weeks compared to 1.86% with semaglutide. All three doses of tirzepatide were statistically superior to semaglutide. Tirzepatide also caused greater weight loss, with the 15-mg group losing 12% of their body weight compared to 6% with semaglutide. [SH review] In a second trial (N=2539) that was designed to evaluate weight loss in obese nondiabetics (average baseline weight 231 lbs), tirzepatide doses of 5 - 15 mg caused weight loss of 15 - 21% over 72 weeks, with the 15-mg group losing an astounding 52 lbs on average. [SH review] The main side effects in both trials were gastrointestinal (nausea, diarrhea, constipation), and most were transient, resolving after the dose titration phase. Dropout rates due to adverse events were low in all groups (< 10%).

Tirzepatide is given as a once-weekly subcutaneous injection. The starting dose is 2.5 mg for 4 weeks followed by an increase to 5 mg. Maintenance dosing ranges from 5 - 15 mg.

Tirzepatide outperformed semaglutide (Ozempic®) in the diabetes trial, although the dose of semaglutide was only 1 mg, and it has since been approved up to 2 mg. Weight loss from tirzepatide is quite impressive (∼ 21%) and greater than what has been seen with Wegovy® (15 - 16%). Currently, tirzepatide is only FDA-approved for diabetes, but a weight-loss indication will surely soon follow. See tirzepatide (Mounjaro) for a complete review.


GLP-1 analogs

Semaglutide (Wegovy®)

Type 2 diabetes