What does this research mean for the field?

In adults with type 2 diabetes, achieving ≥15% body weight reduction with tirzepatide is predicted by higher doses, female sex, younger age, metformin use, and better baseline metabolic profiles, and is associated with greater improvements in cardiometabolic risk factors. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

October 12, 2023Diabetes CareOpen Access

Predictors of ≥15% Weight Reduction and Associated Changes in Cardiometabolic Risk Factors With Tirzepatide in Adults With Type 2 Diabetes in SURPASS 1–4

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Why the study?

Predictors of body weight reduction of ≥15% with tirzepatide and associated clinical parameters across categorical weight reduction tiers in type 2 diabetes were not established.

What are the predictors of ≥15% body weight reduction and associated changes in cardiometabolic risk factors with tirzepatide in adults with type 2 diabetes?

Structured PICO

What are the predictors of ≥15% body weight reduction and associated changes in cardiometabolic risk factors with tirzepatide in adults with type 2 diabetes?

Population

3,188 adults with type 2 diabetes from the phase 3 SURPASS 1-4 clinical trials who were adherent to treatment (≥75% doses received and on treatment at week 40/42). Mean baseline HbA1c ranging from 7.94 to 8.52% and BMI ranging from 31.9 to 34.2 kg/m2.

Intervention

Tirzepatide (5 mg, 10 mg, or 15 mg) once weekly for 40 or 52 weeks.

Outcome

Predictors of body weight reduction of ≥15% and associated changes in cardiometabolic risk factors at week 40/42.surrogate

In patients with type 2 diabetes, higher tirzepatide doses, concurrent metformin use, and better baseline glycemic status predict ≥15% body weight reduction, which is associated with greater improvements in cardiometabolic risk factors.

Limitations

Post hoc analysis design focused on those adherent to treatment
Limited follow-up period that may not be adequate for some to reach the BW plateau
Predictor model lacks postbaseline and genetic data
Studies were too short to see impacts on long-term cardiovascular outcomes
Limited sample size of African American and American Indian/Alaska Native individuals

Implication

May inform tirzepatide patient selection in T2D; hypothesis-generating and requires prospective validation.

Abstract

OBJECTIVE: To identify predictors of body weight (BW) reduction of ≥15% with tirzepatide treatment and to describe associated clinical parameters of participants with type 2 diabetes (T2D) who achieved different categorical measures of BW reduction (<5%, ≥5 to <10%, ≥10 to <15%, and ≥15%) across four studies from the phase 3 SURPASS clinical trial program for T2D. RESEARCH DESIGN AND METHODS: The multivariate model for predictor of a BW reduction of ≥15% included age, sex, race, BW, HbA1c, tirzepatide dose and baseline metformin use, fasting serum glucose, and non-HDL cholesterol. Baseline characteristics and change from baseline to week 40/42 for efficacy parameters were described and analyzed in treatment-adherent participants (≥75% doses administered and on treatment at week 40/42) receiving once weekly tirzepatide (5 mg, 10 mg, or 15 mg) (N = 3,188). RESULTS: Factors significantly associated with achieving a BW reduction of ≥15% with tirzepatide were higher tirzepatide doses, female sex, White or Asian race, younger age, metformin background therapy, and lower HbA1c, fasting serum glucose, and non-HDL cholesterol at baseline. With higher categorical BW reduction, there were greater reductions in HbA1c, triglycerides, ALT, waist circumference, and blood pressure. CONCLUSIONS: Baseline factors associated with a higher likelihood of achieving a BW reduction of ≥15% with tirzepatide were higher tirzepatide doses, female sex, White or Asian race, younger age, metformin background therapy, better glycemic status, and lower non-HDL cholesterol. With greater BW reduction, participants with T2D achieved larger improvements in glycemia and cardiometabolic risk parameters. These findings help inform which people with T2D are most likely to achieve greater BW reduction with improved cardiometabolic risk factors with tirzepatide.