Relationship between body weight change and glycaemic control with tirzepatide treatment in people with type 2 diabetes: A post hoc assessment of the SURPASS clinical trial programme

Abstract Aim To assess the relationship between HbA1c and body weight reductions with tirzepatide treatment (5, 10 or 15 mg). Materials and Methods HbA1c and body weight data at 40 weeks (SURPASS‐1, ‐2 and ‐5) and 52 weeks (SURPASS‐3 and ‐4) were analysed by trial. Results Across the SURPASS clinical trials, HbA1c reductions from baseline were observed in 96%‐99%, 98%‐99% and 94%‐99% of participants treated with tirzepatide 5, 10 and 15 mg, respectively. Moreover, 87%‐94%, 88%‐95% and 88%‐97% of participants, respectively, experienced weight loss associated with HbA1c reductions. Statistically significant associations (correlation coefficients ranging from 0.1438 to 0.3130 across studies; P ≤ .038) between HbA1c and body weight changes were observed with tirzepatide in SURPASS‐2, ‐3, ‐4 (all doses) and ‐5 (tirzepatide 5 mg only). Conclusions In this post hoc analysis, consistent reductions in both HbA1c and body weight were observed in most participants treated with tirzepatide at doses of 5, 10 or 15 mg. A statistically significant but modest association between HbA1c and body weight change was observed in SURPASS‐2, SURPASS‐3 and SURPASS‐4, suggesting that both weight‐independent and weight‐dependent mechanisms are responsible for the tirzepatide‐induced improvement in glycaemic control.