SAN DIEGO — Weekly injections of tirzepatide in adults with type 2 diabetes and overweight or obesity safely led to 12.8% to 14.7% weight loss in the trial after 72 weeks in the SURMOUNT-2 Pivotal Assaya finding that will likely lead to approval of a new weight loss indication for tirzepatide by the US Food and Drug Administration (FDA).
Tirzepatide received in 2022 FDA approval as a treatment for type 2 diabetes in adults, marketed as Mounjaro. The agent, a “gemelacretin” that acts as an agonist at both the glucagon-like peptide-1 (GLP-1) receptor and the glucose-dependent insulinotropic polypeptide (GIP) receptor, also previously scored a decisive victory for loss weight in overweight or obese adults without diabetes at the SURMOUNT-1 Pivotal Assay.
Dr. W. Timothy Garvey
Taken together, the results from SURMOUNT-1 and SURMOUNT-2 appear to make a good argument for an indication for weight loss that will not depend on whether a patient also has type 2 diabetes.
“We anticipate that tirzepatide will be approved by the FDA for weight loss later this year,” said W. Timothy Garvey, MD, principal investigator for SURMOUNT-2, during a press conference here at the 83rd Scientific Session of the American Diabetes Association (ADA). .
Tirzepatide “fills the gap”
Tirzepatide “fills the gap to achieve (medication-driven) weight loss in the range of 15% of baseline weight or better,” Garvey noted, putting it in a favorable position relative to a weekly subcutaneous injection of 2 .4 mg with the GLP-1 agonist semaglutide (Wegovy), which produced an average weight loss from baseline of about 9.6% in people with type 2 diabetes in the Test STEP-2.
Although tirzepatide has not been directly compared for weight loss with any of the several available GLP-1 agonists, reported weight loss numbers appear to favor tirzepatide, said Garvey, director of the Diabetes Research Center at the University of Alabama. in Birmingham.
“If you look at the degree of weight loss in the trials, we see a clinically meaningful difference in weight loss” compared with semaglutide and other agents that only act on the GLP-1 receptor, he noted. (Although cross-trial comparisons of different drugs often have uncertain reliability.)
“The data suggest an incremental effect of tirzepatide” compared to the GLP-1 agonists now approved for weight loss,” said Marlon Pragnell, PhD, vice president of Research and Science, ADA, who was not involved in the studies of tirzepatide.
This is a “step forward in treating people with obesity and type 2 diabetes; it’s a very promising treatment option,” Pragnell said in an interview.
Affordability and access will continue to be “a big problem”
However, Garvey cautioned that access and affordability of tirzepatide, as well as other GLP-1 agonists, remains a major sticking point.
“These drugs are very expensive, more than $1,000 per dose, and this cost limits access … (which is) a big problem,” Garvey noted. US health care payers “don’t want to open the doors (to expensive treatments) for a disorder that is as common as obesity.”
“Access and affordability are always an issue for these drugs,” agreed Janet Brown-Friday, RN, president of Health Care & Education, ADA, who was also not involved in the tirzepatide studies.
Janet Brown-Friday
SURMOUNT-2 randomized 938 adults with type 2 diabetes to being overweight or obese at 77 centers in seven countries, including the United States, between March 2021 and April 2023. The study had two main results: mean percentage change in body weight from baseline to week 72, and the percentage of participants who achieved a weight reduction from baseline of at least 5%, again after 72 weeks.
On test, 12.8% to 14.7% weight loss
Analysis during the trial showed that a 10 mg subcutaneous weekly dose of tirzepatide resulted in an average weight loss of 12.8% from baseline, and a 15 mg subcutaneous weekly dose resulted in an average weight loss of 14. 7% with respect to the initial weight. People randomized to receive a placebo injection averaged a 3.2% drop from their baseline weight after 72 weeks, a finding documenting significant improvements compared to placebo with both doses of tirzepatide.
The percentage achieving at least a 5% reduction in weight from baseline were 79% of those receiving the 10 mg dose of tirzepatide, 83% of those receiving the 15 mg dose, and 32% of those receiving the 10 mg dose of tirzepatide. those receiving placebo, which also represented significant improvements for both doses of tirzepatide compared to placebo.
A 15% or greater reduction in weight from baseline occurred in 40-48% of people receiving tirzepatide compared with 3% of those receiving placebo. A weight reduction of this magnitude from baseline “will prevent a wide range of complications,” Garvey noted.
Simultaneously with the report of the meeting, the results were posted online in the lancet.
Glucose control without severe hypoglycemia
The safety profile of tirzepatide in SURMOUNT-2 was consistent with previous studies of the agent, as well as other medicinal products in the GLP-1 agonist class, with predominant gastrointestinal adverse effects such as nausea and vomiting, especially during the escalation phase of dose. at the start of treatment.
Garvey especially highlighted the general safety of tirzepatide, and in particular its ability to produce clinically important reductions in hemoglobin a1c that averaged more than two percentage points of baseline values without producing a single episode of hypoglycemiaand less than 5% incidence of milder hypoglycemia.
The absence of severe hypoglycemia was “surprising,” Garvey said, especially given that 46% to 49% of people taking tirzepatide in SURMOUNT-2 achieved normalization of their A1c to less than 5.7% on treatment compared to 4% of treated participants. with placebo
The results also showed the benefit of a “great reduction in fasting insulin levels” that averaged a 41% reduction from baseline in those receiving the weekly 15 mg subcutaneous dose of tirzepatide, along with increased insulin sensitivity, Garvey said.
the lancet. Published online June 23, 2023. Text complete
American Diabetes Association (ADA) 83rd Scientific Sessions. Session CT-1.5-SY40. Submitted June 23, 2023.
SURMOUNT-2 was sponsored by Eli Lilly, the company that markets tirzepatide (Mounjaro). Garvey has consulted for and received research funding from Eli Lilly, as well as a consultant or advisor to Boehringer Ingelheim, Novo Nordisk, Pfizer, Fractyl Health, Alnylam Pharmaceuticals, Inogen, and Merck. He has also been an investigator for studies sponsored by Novo Nordisk, Epitomee, Neurovalens, and Pfizer. Pragnell and Brown-Friday have disclosed no relevant financial relationships.
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