The “twincretin” tirzepatide (Mounjaro) has proven successful in SURMOUNT-2, the second pivotal trial for the drug as an antiobesity agent, according to top-line results reported today by tirzepatide’s manufacturer, Lilly, in a press release. The company reveals that tirzepatide achieved both of its primary endpoints in the trial, as well as all its key secondary endpoints.
The findings pave the way for tirzepatide to likely receive US Food and Drug Administration (FDA) approval as a treatment for obesity, perhaps before the end of 2023.
Tirzepatide received FDA approval in May 2022 for the treatment of type 2 diabetes in adults, under the brand name Mounjaro, and some people have already been using it off-label to treat obesity.
Tirzepatide is a dual glucagon-like peptide-1 (GLP-1) agonist and glucose-dependent insulinotropic polypeptide (GIP) agonist. Several GLP-1 receptor agonists are already approved in the United States, including semaglutide, a once-weekly injection, which is approved as Wegovy for patients with obesity and as Ozempic for treatment of type 2 diabetes.
These agents have been incredibly popular among celebrity influencers, and with use of the #Ozempic hashtag and others on social media, this has led to unprecedented use of these products for weight loss, often among those who do not even have obesity or type 2 diabetes. Subsequently, patients with type 2 diabetes and obesity who need them have often struggled to obtain them, owing to shortages following this phenomenon.
SURMOUNT-2: Weight Loss Around 15%, Less Than Seen in SURMOUNT-1
SURMOUNT-2 enrolled 938 adults with overweight or obesity and type 2 diabetes and had dual primary endpoints that both focused on weight loss compared with placebo.
The first completed pivotal trial of tirzepatide for weight loss, SURMOUNT-1, enrolled people with overweight or obesity but no diabetes and had its main results reported in 2022. At the time, as reported by Medscape, the weight loss achieved with tirzepatide, was described as “unprecedented,” with those given the highest dose in that trial (15 mg subcutaneously per week) losing an average of 20%-22% of body weight over 72 weeks, depending on the specific statistical analysis used.
For SURMOUNT-2’s first primary endpoint, 72 weeks of weekly subcutaneous injections with tirzepatide at dosages of 10 mg or 15 mg led to an average weight loss from baseline of 13.4% and 15.7%, respectively, compared with an average loss of 3.3% from baseline in the placebo-treated control arm.
For the second primary endpoint, 81.6% of people on the 10-mg dose and 86.4% on the 15-mg dose achieved at least 5% weight loss from baseline, compared with 30.5% of controls who had at least 5% weight loss from baseline.
In one key secondary endpoint, tirzepatide at dosages of 10 mg or 15 mg weekly produced at least a 15% cut in weight from baseline in 41.4% and 51.8% of participants, respectively, compared with a 2.6% rate of this endpoint in the placebo controls.
So the extent of weight loss seen in in SURMOUNT-2 was somewhat less than was reported in SURMOUNT-1, a finding consistent with many prior studies of incretin-based weight-loss agents, which seem to pack a more potent weight loss punch in people without type 2 diabetes.
Lilly did not specifically report the treatment effect of tirzepatide on A1c in SURMOUNT-2, only saying that the effect was similar to what had been seen in the series of five SURPASS trials that led to the approval of tirzepatide for type 2 diabetes.
Lilly also reported that the safety profile of tirzepatide in SURMOUNT-2 generally matched what was seen in SURMOUNT-1 as well as in the SURPASS trials. The most common adverse events in SURMOUNT-2 involved gastrointestinal symptoms, such as nausea, diarrhea, and vomiting; these were generally mild to moderate in severity and clustered during the dose-escalation phase at the start of treatment. Treatment discontinuations due to adverse effects were 3.8% on the 10-mg dosage, 7.4% on the 15-mg dosage, and 3.8% on placebo.
SURMOUNT-2 enrolled patients in the United States, Puerto Rico, and five other countries. All participants also received interventions designed to reduce their calorie intake and increase their physical activity.
More SURMOUNT-2 Results at ADA in June
Lilly also announced that researchers would report more complete results from SURMOUNT-2 at the 2023 Scientific Sessions of the American Diabetes Association, being held in San Diego in late June, and publish the findings in a major medical journal.
Results from two additional phase 3 trials of tirzepatide in people with overweight or obesity, SURMOUNT-3 and SURMOUNT-4, are expected later in 2023.
Lilly started an application to the FDA for an indication for weight loss in October 2022 under a fast track designation by the agency, and the data collected in SURMOUNT-2 are expected to complete this application, which would then be subject to an FDA decision within about 6 months. Lilly said in its April 27 press release that it anticipates an FDA decision on this application may occur before the end of 2023.
SURMOUNT-2 and all of the other tirzepatide trials were sponsored by Lilly.
Mitchel L. Zoler is a reporter for Medscape and MDedge based in the Philadelphia area. @mitchelzoler
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