Key Takeaways:

Patients who responded early to tirzepatide treatment, achieving at least 5% weight loss within 8 weeks, experienced greater weight loss and cardiometabolic improvements overall.
The most substantial benefits were observed in early responders, particularly those on higher doses of tirzepatide.

Study Overview:

At ObesityWeek 2024, Dr. Tina K. Thethi from the AdventHealth Diabetes Institute presented findings from a post hoc analysis of the SURMOUNT-1 and SURMOUNT-2 trials. The analysis evaluated weight loss and cardiometabolic improvements in early responders (defined as patients achieving 5% or more weight loss within 8 weeks) versus non-early responders to tirzepatide (Mounjaro/Zepbound, Eli Lilly).

Background:
Tirzepatide has shown significant efficacy in reducing body weight and improving cardiometabolic parameters in individuals with obesity, overweight, and diabetes. Previous studies suggest that early weight loss during treatment is predictive of long-term success.

Study Details and Findings:

Trial Design:

SURMOUNT-1: Included adults with overweight or obesity (without diabetes) and at least one weight-related comorbidity. Patients were randomized to tirzepatide (5 mg, 10 mg, or 15 mg) or placebo for 72 weeks. Mean age: 45 years; two-thirds women.
SURMOUNT-2: Focused on adults with a BMI of 27 kg/m² or higher, diabetes, and HbA1c between 7% and 10% on stable therapy. Patients were randomized to tirzepatide (10 mg, 15 mg) or placebo for 72 weeks. Mean age: 54 years; about half were women.

Key Results:

Weight Loss:
- Early responders in SURMOUNT-1 experienced 23.3% weight loss by week 72, compared to 14.6% among non-early responders (P < .001).
- In SURMOUNT-2, early responders lost 20%, versus 10.8% among non-early responders (P < .001).
- Weight loss was consistent across tirzepatide doses, with higher doses yielding greater results.
HbA1c Reduction:
- Early responders saw larger HbA1c reductions compared to non-early responders in both SURMOUNT-1 (0.5% vs. 0.41%; P < .001) and SURMOUNT-2 (2.46% vs. 2.03%; P < .001).
Cardiometabolic Parameters:
- Early responders showed greater reductions in systolic and diastolic blood pressure, serum alanine aminotransferase, and triglycerides, along with a greater increase in HDL cholesterol (P < .05 for all).
- LDL cholesterol improved in SURMOUNT-1 but increased in SURMOUNT-2, with no significant difference between early and non-early responders.
- Non-HDL cholesterol was reduced in both trials but showed significantly greater reductions among early responders only in SURMOUNT-1 (P < .01).

Clinical Implications:

Tirzepatide demonstrated significant benefits in weight loss and cardiometabolic health regardless of early response. However, patients who achieved 5% or more weight loss by week 8 showed enhanced outcomes, emphasizing the importance of early intervention.

“This analysis underscores the value of personalized treatment plans for patients,” said Thethi. “Patients who lose weight early on are more likely to experience greater improvements in weight and cardiometabolic parameters. These findings can guide clinicians in setting individualized therapeutic goals.”