Achieving Normoglycemia With Tirzepatide: Analysis of SURPASS 1-4 Trials

<bold>Objective: </bold>Tirzepatide is a novel single-molecule glucose-dependent insulinotropic polypeptide/glucagon-like peptide 1 receptor agonist, which demonstrated unprecedented improvements in glycemic control and body weight reduction, 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. <bold>Research design and methods: </bold>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 = 3,229). 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%. <bold>Results: </bold>Tirzepatide-treated participants who achieved HbA1c <5.7% were slightly younger, with a shorter duration of diabetes and lower HbA1c value at baseline compared with 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. <bold>Conclusions: </bold>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.