Time to Reach Glycaemic and Body Weight Loss Thresholds with Tirzepatide in Patients with Type 2 Diabetes: A Pre-planned Exploratory Analysis of SURPASS-2 and SURPASS-3.

Abstract

Tirzepatide, a once-weekly glucose-dependent insulinotropic polypeptide/glucagon-like peptide-1 receptor agonist, provides clinically meaningful improvements in glycaemic control and body weight loss in people with type 2 diabetes. The early efficacy profile of tirzepatide after treatment initiation is of interest. In this exploratory pre-planned analysis, we evaluated the time to achieve glycaemic control and body weight loss thresholds with tirzepatide. In two randomised studies, we compared time to achieve HbA1c (< 7.0% and ≤ 6.5%) and weight loss (≥ 5%, SURPASS-2 only) thresholds among people treated with tirzepatide (5, 10, and 15mg), semaglutide 1mg in SURPASS-2, and titrated insulin degludec in SURPASS-3. Longitudinal logistic regression models were used to explore the proportion of participants achieving HbA1c and body weight loss thresholds at 4, 12, and 24weeks. The time to achieve these thresholds was analysed and compared between groups using the Cox proportional-hazards model. Overall, greater proportions of participants achieved the HbA1c and body weight loss thresholds at 4, 12, and 24weeks with tirzepatide compared with semaglutide 1mg and insulin degludec. The median time to achieve HbA1c < 7.0% (8.1weeks with each tirzepatide dose, 12.0weeks with semaglutide 1mg, and 12.1weeks with insulin degludec) and ≤ 6.5% (12.1, 15.7, and 24.1weeks, respectively) was faster with tirzepatide than semaglutide 1mg and insulin degludec. In SURPASS-2, the median time to first achieve a body weight loss of ≥ 5% was faster with tirzepatide 5mg (16.0weeks) and 10 and 15mg (12.4weeks) than with semaglutide 1mg (24.0weeks). Analyses of data from SURPASS-2 and -3 revealed that tirzepatide treatment enabled more people with type 2 diabetes to achieve glycaemic thresholds and these were achieved faster than with semaglutide 1mg or insulin degludec. Tirzepatide-treated participants also achieved a body weight loss of ≥ 5% significantly faster with tirzepatide than with semaglutide 1mg. NCT03987919; NCT03882970.