Mounjaro Shows ‘Significant and Superior Weight Loss’ in Latest Studies

Eli Lilly’s potential blockbuster weight loss drug Mounjaro has posted a new bar for effectiveness in its latest clinical trial.

Participants in the company's phase 3 clinical trials for tirzepatide, Mounjaro’s generic version, lost around 26% of their total weight over 84 weeks when paired with a significant diet and exercise regimen.

A second trial found that just the drug alone could assist users in losing 22.5% of their body weight over 88 weeks.

The trials, called SURMOUNT-3 and SURMOUNT-4, both included hundreds of participants with obesity or who were overweight with weight-related comorbidities, excluding type 2 diabetes. Mounjaro was initially developed and marketed for type 2 diabetes patients.

Participants in SURMOUNT-3 followed a 12-week “intensive lifestyle intervention” program that included a low-calorie diet, exercise and weekly counseling sessions. At the end of the 12 weeks, participants were randomized to either take a placebo or take tirzepatide for a following 72-week period. 

Those in the placebo group experienced a mean weight regain of 3.3% during the 72-week period, while those taking the drug continued to lose weight. In the end, the group taking tirzepatide saw their weight drop over a quarter on average.

The SURMOUNT-4 trial took a slightly different approach. In that trial, all participants first took tirzepatide for 36 weeks; followed by a 52-week period during which the group either continued to take tirzepatide or had it replaced with a placebo. This trial did not involve a diet or exercise interventions, like SURMOUNT-3.

 After the 36-week lead-in period, the group achieved a 21.1% mean weight loss. Those who next took the placebo experienced a mean weight regain of 14.8%; while those who stayed on tirzepatide continued to lose weight. At the end of the 88-week period, those who took tirzepatide for the entire period achieved a total of 26% mean body weight loss.

"The results of SURMOUNT-3 and -4 showed the highest level of weight loss observed in the SURMOUNT program to date," Jeff Emmick, M.D., Ph.D., senior vice president, product development for Eli Lilly said in a statement.

“The findings from SURMOUNT-3 challenge the notion that patients living with obesity or overweight can achieve their weight loss goals with diet and exercise alone,” Dr. Emmick continued. “Additionally, the findings from SURMOUNT-4 reinforce that obesity should be regarded like other chronic diseases where chronic therapy may be needed to maintain treatment benefits."

Tirzepatide works differently than competitors Ozempic and Wegovy – which both use semgalutide as their active ingredient. 

Semaglutide drugs are a GLP-1 (glucagon-like peptide-1) receptor agonist, whereas tirzepatide acts both as a GIP (glucose-dependent insulinotropic polypeptide) and GLP-1 (glucagon-like peptide-1) receptor agonist. All of these drugs act on both the gut and the brain, reducing the desire for food as well as slowing down gastric emptying, so users feel fuller longer.

However, tirzepatide activates more hormone systems in the brain, a change which makes some hope it will be significantly more effective.

In earlier trials, Mounjaro users dropped 15.7% of their weight over a 72-week period. Users of a semaglutide on average lose about 15% of their body weight over 68 weeks, according to earlier clinical trials. 

Weight loss drugs like Ozempic, Wegovy, and Mounjaro have continued to be extremely popular in recent years — even amid reports of potential negative mental health side effects, cases of gastroparesis and the possibility of regaining the weight.

Tirzepatide was approved by the Food and Drug Administration under the brand name Mounjaro on May 13, 2022. Like competitor drugs, this one is administered as a once-weekly injection. 

Eli Lilly is also currently testing a weight loss drug called retatrutide, which could prove to be even more effective than any other product on the market. That drug was in phase 2 clinical trials as of June.