Tirzepatide causes massive weight reduction in sufferers with weight problems

The combination of GIP and GLP-1 receptor agonist tirzepatide (Mounjaro) could soon be the next new treatment option for people who are overweight or obese, researchers reported.

In the 72-week phase III clinical trial SURMOUNT-1, subjects with obesity but without diabetes given 15 mg of the once-weekly injectable had a mean percent weight change of -20.9% (95% CI -21.8 to – 19.9%) vs -3.1% (95% CI -4.3 to -1.9) with placebo, according to Ania M. Jastreboff, MD, PhD, Yale University School of Medicine in New Haven, and Colleagues.

People who received the two lower doses also saw a significant mean decrease in body weight at the end of the study compared to placebo:

  • 5 mg: -15.0% (95% CI -15.9 to -14.2)
  • 10 mg: -19.5% (95% CI -20.4 to -18.5)

Overall, 85%, 89%, and 91% of patients on the 5 mg, 10 mg, and 15 mg doses achieved a clinically meaningful weight reduction of 5% or more, compared to only 35% of placebo patients receiving achieved the same. In addition, 50% and 57% of adults at the two higher doses achieved a weight loss of 20% or more, compared with just 3% on placebo.

Developer Eli Lilly announced top-line data from the study earlier last month. The full results were presented at the American Diabetes Association (ADA) annual meeting and simultaneously published in the New England Journal of Medicine.

“This is a new era for treating obesity,” Jastreboff said during an ADA press conference. “There were first-generation drugs, second-generation drugs, that was around 2010 to 2020. Starting last year with semaglutide [Wegovy] and now Tirzepatide, this is a new era for obesity treatment.”

“These drugs are much more effective than any other drug that we currently have to treat obesity. They are clearly exceeding the target of at least 5% weight reduction,” she stressed. “What we really need to focus on is [that] this is a new era for our patients; This is a new era for physicians who care about patients with obesity – and we all do – and we have the tools now and will have even more tools in the future to be able to treat our patients with obesity.”

For the efficacy estimate, the mean body weight reductions for the 5 mg, 10 mg, and 15 mg doses were 16.1 kg (35.5 lb), 22.2 kg (48.9 lb), and 23, respectively .6 kg (52.0 lb). . In the subgroup of patients who underwent dual-energy X-ray absorptiometry (DXA) scanning, there was a 25.7% greater reduction in total body fat mass compared to placebo.

In addition to weight loss, tirzepatide treatment resulted in improvements in waist circumference, systolic and diastolic blood pressure, fasting insulin levels, and lipid levels. According to the authors, physical function SF-36 scores also increased more with active treatment.

As expected for a GLP-1 receptor agonist, the most common adverse events (AEs) were gastrointestinal: nausea, diarrhea and constipation. There were four cases of court-confirmed pancreatitis, one in each of the study arms including placebo.

Most GI AEs occurred during the dose-escalation phase and then decreased over time, Jastreboff said. She explained that clinicians need to work with their patients to manage these AEs and see if down-titration is needed or if patients are eating past the point of satiety, which is spurring these AEs.

“Welcome to GLP-1 receptor agonists,” commented Robert Eckel, MD, of the University of Colorado, during the press conference.

Tirzepatid, the first of its kind in this class of GLP-1/GIP combination drugs, was approved by the FDA for type 2 diabetes in May based on results from the SURPASS clinical program.

The active ingredient is intended to follow in the footsteps of other GLP-1 receptor agonists that have since been used not only for diabetes indications but also for weight control. Some of these options include liraglutide 30 mg (Saxenda) and the blockbuster semaglutide 2.4 mg, both of which are approved as lifestyle modification supplements.

“The kind of comparative study that’s really needed is a randomized controlled trial of semaglutide or tirzepatide versus metabolic surgery,” said Eckel, who was not involved in the current study. “This is urgently needed now [help] Patients individually make the best choice for themselves.”

The study enrolled 2,539 overweight or obese adults (baseline BMI 38) without diabetes, although 40% had pre-diabetes. The overall age of the study population was approximately 45 years and they were predominantly female and white.

Jastreboff highlighted the difference in weight loss observed between this study and the SURPASS clinical program, which evaluated tirzepatide in people with diabetes. In the latter, patients taking tirzepatide 15 mg saw an average weight loss of 8.8 kg (19.4 lb).

“Weight loss in people with diabetes is less than in people who don’t already have diabetes,” she explains. “For patients who have already developed type 2 diabetes, it’s different that they lose less weight with these drugs.”

“I think that’s incredibly important because what kind of message does that send,” she said. “It sends the message that we are treating patients too late. We should be treating patients if they have obesity before they develop type 2 diabetes. We can do more to help their health.”

“I think we should treat patients earlier,” she said.

Jastreboff added that SURMOUNT-1 will be continued for an additional 2 years for the 40% of participants with prediabetes to see if they had different baseline weight reductions than those without prediabetes.

  • Kristen Monaco is a staff writer focused on endocrinology, psychiatry, and nephrology news. She is based out of the New York office and has been with the company since 2015.


The process was funded by Eli Lilly. Some co-authors are company employees.

Jastreboff and co-authors disclosed several industry relationships, including Eli Lilly.

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