Early weight loss with tirzepatide predictive of larger cardiometabolic benefits later on
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Key takeaways:
- The weight loss and cardiometabolic benefits of tirzepatide were greater among early responders to treatment.
- The strongest benefits were observed among patients with 5% or more weight loss at 8 weeks.
SAN ANTONIO — Tirzepatide confers significant weight loss and cardiometabolic benefits for patients with diabetes and overweight or obesity, especially for those who lose more weight earlier during treatment, a speaker reported.
At ObesityWeek, Tina K. Thethi, MD, MPH, associate investigator at the AdventHealth Translational Research Institute and endocrinologist at the AdventHealth Diabetes Institute in Orlando, discussed differences in weight loss and cardiometabolic parameters among early- and non-early responders to tirzepatide (Mounjaro/Zepbound, Eli Lilly) in the SURMOUNT-1 and SURMOUNT-2 trials. Early responders were defined as those who experienced 5% or more weight loss during 8 weeks of treatment.
“Tirzepatide has led to significant body weight reductions and improvements in cardiometabolic parameters in those with obesity or overweight but without diabetes,” Thethi said during the presentation. “Early response to weight-loss interventions has been shown to predict long-term weight loss. With that background in mind, this post hoc analysis was done to assess if early weight loss ... was associated with greater improvements in weight and cardiometabolic parameters in those treated with tirzepatide in SURMOUNT-1 and SURMOUNT-2.”
SURMOUNT-1 was a randomized, double-blind, placebo-controlled trial for which patients with overweight and one weight-related comorbidity or obesity and without diabetes were randomly assigned to 72 weeks of tirzepatide 5 mg, 10 mg or 15 mg or placebo. The mean age was 45 years and about two-thirds of patients were women.
SURMOUNT-2 included adults with a BMI of 27 kg/m2 or higher, diabetes and HbA1c of 7% to 10% on a stable diabetes therapy who were randomly assigned to once-weekly tirzepatide 10 mg, tirzepatide 15 mg or placebo for 72 weeks. The mean age was 54 years and about half of patients were women.
As Healio previously reported, adults with overweight or obesity without diabetes in the SURMOUNT-1 trial experienced an approximately 20.9% weight loss at 72 weeks with 15 mg tirzepatide, and participants in SURMOUNT-2 assigned to tirzepatide 10 mg lost 12.8% of body weight; those receiving tirzepatide 15 mg lost 14.7% of body weight; and both tirzepatide groups experienced a 2.1% reduction in HbA1c at 72 weeks.
For the present post hoc analysis, Thethi and colleagues pooled data from both SURMOUNT trials to evaluate the weight-related and cardiometabolic impact of early response to tirzepatide.
Early responders had a greater percentage weight loss at 72 weeks compared with non-early responders in both SURMOUNT-1 (23.3% vs. 14.6%; P < .001) and SURMOUNT-2 (20% vs. 10.8%; P < .001), and weight loss was higher among early responders taking higher doses of tirzepatide, according to the presentation.
Thethi reported that a greater proportion of early responders to tirzepatide achieved their weight reduction targets at 72 week compared with non-early responders (P < .001).
The weight-loss findings were consistent regardless of tirzepatide dose, she said.
Early responders had a greater percentage HbA1c reduction at 72 weeks compared with non-early responders in both SURMOUNT-1 (0.5% vs. 0.41%; P < .001) and SURMOUNT-2 (2.46% vs. 2.03%; P < .001), and a greater proportion of early responders achieved their HbA1c goals compared with non-early responders, according to the presentation.
Thethi and colleagues reported greater reductions in systolic blood pressure, diastolic BP, serum alanine aminotransferase and triglycerides among early responders compared with non-early responders in both SURMOUNT-1 and -2 and a greater increase in HDL cholesterol (P for all < .05).
LDL cholesterol was significantly lowered in both groups in SURMOUNT-1 and significantly increased in SURMOUNT-2, but there was no significant differences between early and non-early responders.
Moreover, non-HDL cholesterol was reduced in both trials, but the difference between early and non-early responders was only significant in SURMOUNT-1, trending toward greater reductions among early responders (P < .01).
“Tirzepatide treatment was associated with a significant weight reduction and improved cardiometabolic parameters, be it whether you were an early responder or not, you had a significant decline in weight and cardiometabolic parameters compared with baseline at week 72,” Thethi said during the presentation. “If you lost more than 5% of the weight by week 8, those subjects by all means had a greater reduction in body weight and cardiometabolic parameters as compared with those that were non-early responders. ... This analysis is relevant for all of us as clinicians as we sit across our patients, making decisions that are personalized therapeutic goals. It’s not one-size-fits-all.”
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Thethi T, et al. Oral-075. Presented at: ObesityWeek; Nov. 3-6, 2024; San Antonio.
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