'Achieving Normoglycemia with Tirzepatide: Analysis of SURPASS 1-4 trials'

Objective

Tirzepatide is a novel single-molecule GIP/GLP-1 receptor agonist, that demonstrated unprecedented improvements in glycemic control and body weight loss, in the SURPASS phase 3 program. In this exploratory analysis, we aimed to characterize tirzepatide-treated participants who achieved HbA1c <5.7% and evaluate changes in clinical markers associated with long-term cardiometabolic health.

Research design and methods

Baseline characteristics and change from baseline to Week 40 for several efficacy and safety parameters were analyzed according to HbA1c attainment category (<5.7%, 5.7-6.5% and >6.5%) using descriptive statistics in participants taking ≥75% of treatment doses, without rescue medication, in the SURPASS 1-4 trials (N=3229). Logistic regression models with tirzepatide doses adjusted as a covariate, were used to obtain odds ratios and assess the impact of patient characteristics achieving an HbA1c <5.7%.

Results

Tirzepatide-treated participants who achieved HbA1c <5.7% were slightly younger, with shorter duration of diabetes and lower HbA1c value at baseline compared to those who did not achieve HbA1c <5.7%. In addition, they showed greater improvements in HbA1c, body weight, waist circumference, blood pressure, liver enzymes, and lipid parameters without increasing hypoglycemia risk.

Conclusions

Normoglycemia was unprecedently achieved in a significant proportion of participants in the SURPASS clinical program, without increasing hypoglycemia risk, and was associated with an overall improvement in metabolic health.