A recently approved diabetes drug being clinically investigated for its effects on body weight in obese and overweight people has delivered "substantial and sustained reductions in body weight" in a phase 3 clinical trial, according to results now published in The New England Journal of Medicine.

Tirzepatide, developed by American pharmaceutical company Eli Lilly and Company (Lilly), is a once-weekly injection under the skin, originally developed for type 2 diabetes treatment.

While not yet indicated for this use, it appears to also promote weight loss by mimicking the effects of natural hormones called incretins. These hormones lower blood sugar after we eat, in addition to regulating metabolic processes related to digestion.

Data on the latest clinical trial were originally publicized by Lilly in late April, but have now been presented in further detail at the American Diabetes Association symposium, and undergone peer review.

According to the researchers, bariatric surgery "results in weight reduction of approximately 25 to 30 percent at 1 to 2 years", while in the current study, just over 36 percent of participants receiving 15 mg of the drug reached a weight reduction of 25 percent or more, making the drug's impact similar to results from invasive surgery.

Tirzepatide, sold under the product name Mounjaro, was approved by the FDA for type 2 diabetes treatment on May 13 this year; the drug is a synthetic combination of two particular incretins, called GLP-1 (glucagon-like peptide-1) and GIP (glucose-dependent insulinotropic polypeptide).

The former hormone, GLP-1, is the basis of the anti-diabetes medication semaglutide, which was approved in the US as a weight-loss drug in 2021, representing the first time the FDA had endorsed a new treatment for weight loss in several years.

That approval was granted on the back of results described as a 'game-changer' for weight loss, but it looks like tirzepatide's formulation – thanks to the addition of GIP alongside GLP-1 – might well improve matters even further.

In Phase 3 results from the ongoing SURMOUNT-1 clinical trial investigating the effects of tirzepatide, researchers enrolled 2,539 participants who were either overweight or obese (with one weight-related comorbidity but without type 2 diabetes).

The participants received tirzepatide or a placebo over the course of 72 weeks, along with support to follow a reduced-calorie diet and increase their levels of physical activity.

Tirzepatide was administered at one of three different doses (either 5, 10, or 15 milligrams in the weekly injection), but all three groups saw significant levels of weight loss over the course of the study.

On the highest dose (15 mg), participants saw average weight reductions of 22.5 percent of their body weight (24 kg or 52 lb), while the 10 mg dose achieved 21.4 percent weight loss (22 kg or 49 lb), and 5 mg saw a 16 percent body weight reduction (16 kg or 35 lb).

By comparison, the placebo group lost only 2.4 percent of their body weight (2 kg or 5 lb). Previously, the semaglutide weight loss trials averaged a roughly 17 percent weight loss.

"Tirzepatide is the first investigational medicine to deliver more than 20 percent weight loss on average in a phase 3 study," said clinical research physician Jeff Emmick, the vice president of product development at Lilly.

Study in the SURMOUNT-1 trial is ongoing, alongside related SURMOUNT trials, the results of which are expected to be announced in 2023.

However, we do already know that tirzepatide does not agree with everyone who takes it. While the averaged weight-loss results do appear to slightly outperform treatment with semaglutide, and are about on par with the weight loss patients might expect from bariatric surgery, some participants in the tirzepatide arm experienced adverse effects.

Depending on dose, up to one-third of the group on tirzepatide experienced nausea, while diarrhea was also relatively common (for 18.7–23 percent of participants). Some people also experienced vomiting and constipation, although it's worth noting only a small percentage of participants left the study due to these effects.

Yet another potential barrier to stomaching tirzepatide is the issue of price – assuming subsequent research results convince the FDA to approve the drug for weight-loss patients as well.

As others have noted, semaglutide – sold as a weight-loss drug under the brand-name Wegovy by Danish pharmaceutical company Novo Nordisk – sells for over US$1,300 per month, and very few patients can afford such an expensive medication, especially when drugs like this are rarely covered by health insurance.

In late May, a Lilly spokesperson confirmed that Mounjaro would have a list price of US$974.33 per week, regardless of dose. As with other brilliant, potentially life-changing medications, the question of access once again becomes highly relevant.

Aside from the economics, the impressive results of medications like tirzepatide nonetheless suggest we might soon be able to transform the treatment of obesity – a complex and harmful epidemic that has resisted our control for decades.

If we can realize that promise, and ensure equitable access to this new generation of obesity medications, we stand to improve the health of millions of people around the world, researchers say.

"Continued development of tirzepatide and similar agents could portend a sea change in obesity treatment," Scott Kahan, the director of the National Center for Weight and Wellness in Washington, DC, told Healio in May.

"Similar to how cholesterol and heart disease management was transformed by the advent of statin medications and how HIV management was transformed by antiretroviral medications."

The study has been published in NEJM.

A version of this article was originally published on 9 May 2022, and has been updated with new details.