SURMOUNT-2: Tirzepatide confers about 15% weight loss in adults with obesity and diabetes
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Key takeaways:
- At 72 weeks, adults receiving 10 mg tirzepatide lost 12.8% of body weight and those receiving 15 mg lost 14.7% of body weight.
- A 2.1% HbA1c reduction was observed in both tirzepatide groups.
SAN DIEGO — Adults with obesity and type 2 diabetes achieved a 14.7% weight loss at 72 weeks with 15 mg tirzepatide, according to data from the SURMOUNT-2 trial presented at the American Diabetes Association Scientific Sessions.
In a phase 3 randomized controlled trial, more than 60% of adults with obesity and type 2 diabetes lost at least 10% of their body weight at 72 weeks if they were receiving 10 mg or 15 mg tirzepatide (Mounjaro, Eli Lilly), and HbA1c dropped by 2.1% in both tirzepatide groups at 72 weeks. W. Timothy Garvey, MD, FACE, MABOM, professor of medicine at the University of Alabama (UAB) at Birmingham and director of the UAB Diabetes Research Center, said the findings from SURMOUNT-2 showed that tirzepatide could provide superior benefits when compared with currently available obesity medications for people with type 2 diabetes.
“This is a therapeutic gap that tirzepatide could fill,” Garvey said during a press conference. “We really want medicines in diabetes to get weight loss into the 15% range or higher. We know at that degree of weight loss that’s sufficient to treat and prevent a broad array of obesity-related complications.”
Trial designed to focus on weight management in type 2 diabetes
As Healio previous reported from the SURMOUNT-1 randomized controlled trial, adults with obesity and no diabetes lost up to 20.9% of their body weight at 72 weeks with 15 mg tirzepatide. Similarly, findings from the SURPASS series of trials found tirzepatide was associated with significantly greater weight loss compared with placebo. However, Juan P. Frias, MD, medical director and principal investigator at Velocity Clinical Research in Los Angeles, said the SURPASS trials were designed primarily to assess glycemic control and not weight loss. This created a need for the SURMOUNT-2 trial.
“These patients did not have calorie-deficit diets,” Frias said of SURPASS participants during the presentation. “They did not have aggressive management by dietitians. Some, relatively few of these patients, had BMIs of less than 27 kg/m2, and the duration of the trials were relatively short compared with obesity trials.”
In SURMOUNT-2, researchers enrolled 938 adults with a BMI of 27 kg/m2 or higher, type 2 diabetes and an HbA1c between 7% and 10% who were on a stable diabetes therapy (mean age, 54.2 years; 51% women, 76% non-Hispanic white). Participants could not have more than a 5 kg change in body weight in the 3 months before screening or be taking another anti-obesity medication. Participants were randomly assigned, 1:1:1, to 10 mg tirzepatide, 15 mg tirzepatide or placebo once weekly. All participants received lifestyle intervention for the 72-week duration of the trial. Researchers analyzed percent change in body weight from baseline to 72 weeks and the percentage of participants achieving at least 5%, 10%, 15% and 20% weight loss at 72 weeks. Changes in HbA1c, fasting glucose, waist circumference, systolic blood pressure and fasting lipids were also analyzed. Treatment-emergent adverse events, serious adverse events and level 2 and level 3 hypoglycemia were examined as safety endpoints.
The findings were simultaneously published in The Lancet.
More than one-third of adults receiving tirzepatide lose 15% or more body weight
In the treatment-regimen estimand, adults receiving tirzepatide lost 12.8% of their body weight with the 10 mg dose and 14.7% of their body weight with the 15 mg dose compared with a 3.2% weight loss in the placebo group (P < .0001 for both). A 5% or greater weight loss was achieved by 79.2% of the 10 mg tirzepatide group and 82.8% of the 15 mg tirzepatide group compared with 32.5% for placebo. A 10% or greater weight loss was observed in 60.5% of the 10 mg tirzepatide group and 64.8% of the 15 mg tirzepatide group compared with 9.5% with placebo, and a 15% or greater weight loss was achieved by 39.7% of the 10 mg tirzepatide group and 48% of the 15 mg tirzepatide group compared with 2.7% of the placebo group. A 20% or greater weight loss was attained by 21.5% of those receiving 10 mg tirzepatide and 30.8% receiving 15 mg tirzepatide.
“In the exploratory endpoint, 17.2% of patients achieved greater than 25% weight reduction,” Garvey said during a presentation.
Waist circumference decreased by 13.1 cm with 15 mg tirzepatide and by 10.8 cm with 10 mg tirzepatide compared with a 3.3 cm waist circumference reduction with placebo (P < .0001 for both). The mean BMI reduction was 5.4 kg/m2 for the 15 mg tirzepatide group and 4.7 kg/m2 for the 10 mg tirzepatide group compared with a 1.2 kg/m2 reduction with placebo (P < .0001 for both).
In the treatment-regimen estimand, adults receiving both 10 mg and 15 mg tirzepatide had a 2.1% reduction in HbA1c at 72 weeks compared with a 0.5% reduction in the placebo group. An HbA1c of less than 7% was achieved by 86.9% of adults receiving 10 mg tirzepatide and 84.2% of those in the 15 mg tirzepatide group compared with 36.2% of those receiving placebo. Normal glycemic levels, defined as having an HbA1c of less than 5.7%, were achieved by 46% of adults in the 10 mg tirzepatide group and 48.6% of the 15 mg tirzepatide group compared with 3.9% of those receiving placebo.
“I never thought we’d see normalization of HbA1c in diabetics with this degree of weight loss and no severe hypoglycemia,” Garvey said.
In lipid parameter data with the two tirzepatide groups pooled together, researchers observed a 27.2% decline in triglycerides, a 5.9% decrease in non-HDL cholesterol and a 9% increase in HDL cholesterol for adults receiving tirzepatide. Those receiving tirzepatide also had greater reductions in both systolic and diastolic BP compared with placebo.
No difference in adverse events, hypoglycemia
Treatment-emergent adverse events were reported by 78% of adults in the 10 mg tirzepatide group and 71% of the 15 mg group compared with 76% of adults receiving placebo. Gastrointestinal disorders were the most common adverse events reported with tirzepatide. Of all participants, 7% reported serious adverse events with no difference between the tirzepatide and placebo groups.
There were no cases of severe hypoglycemia reported in the trial. Level two hypoglycemia was reported by 11 people in the 10 mg tirzepatide group and 15 in the 15 mg tirzepatide group compared with four in the placebo group.
Naveed Sattar, MD, PhD, professor of metabolic medicine in the Institute of Cardiovascular & Medical Sciences at the University of Glasgow in the U.K., said the overall incidence of gallbladder disease-related adverse events was low. There were three cases of pancreatitis in the trial, with no difference between the placebo and tirzepatide groups. Researchers did observe small increases in pulse rate with both 10 mg and 15 mg tirzepatide, but Sattar said those increases are consistent with what has been previously observed with other GLP-1 receptor agonists.
“The tolerability and safety profile of tirzepatide in people living with obesity or overweight and type 2 diabetes was consistent with that observed in the SURPASS studies and with other incretin-based therapies for obesity,” Sattar said during the presentation.
More research needed on durability, further benefits
Ildiko Lingvay, MD, MPH, MSCS, professor of medicine at the University of Texas Southwestern Medical Center in Dallas, discussed how the findings from SURMOUNT-2 were fairly similar to what researchers previously observed in the SURPASS trials.
“Is it déjà vu? I think very much so,” Lingvay said during the presentation. “HbA1c reduction is pretty identical. Weight-loss reduction is identical if extrapolated to 72 weeks. There’s a slightly faster response in SURMOUNT-2, both on the weight and the HbA1c side and I think that’s because of the intensive lifestyle modification.”
Lingvay also displayed a comparison between findings from SURMOUNT-2 and the STEP-2 trial analyzing the effects of semaglutide 2.4 mg (Wegovy, Novo Nordisk) in adults with obesity and type 2 diabetes. The data revealed a greater degree of weight loss and HbA1c reduction in SURMOUNT-2 compared with STEP-2. During a press conference, Garvey said he felt that the data on tirzepatide from SURMOUNT-1 and SURMOUNT-2 were superior to what has been observed in other agents.
“The difference we’re seeing is going to be clinically significant for many patients,” Garvey said during a press conference. “Not all patients need the ‘big bomb’ in terms of weight loss. I was the lead author on the [American Association of Clinical Endocrinology] obesity treatment guidelines and we advanced a complications-centric approach to treating obesity. It wasn’t just how many kilograms you lost, it’s losing sufficient weight to treat or prevent complications of disease.”
Lingvay said there are several questions still to answer, including whether weight loss with tirzepatide is durable past 72 weeks, what potential cardiovascular and renal benefits tirzepatide may provide and whether tirzepatide will confer long-term benefits on disease progression and as primary prevention for microvascular and macrovascular complications if it is prescribed earlier in younger patients.
Other data on common pathophysiology, adherence to medication and health care cost savings are still needed. Lingvay said a cost-savings study is especially important due to insurance companies increasingly opting to decline coverage for obesity medications.
Reference:
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Garvey WT, et al. SURMOUNT-2 trial results and potential role of tirzepatide in treating obesity in type 2 diabetes. Presented at: American Diabetes Association Scientific Sessions; June 23-26, 2023; San Diego (hybrid meeting).
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