Efficacy and tolerability of tirzepatide, a dual glucose‐dependent insulinotropic peptide and glucagon‐like peptide‐1 receptor agonist in patients with type 2 diabetes: A 12‐week, randomized, double‐blind, placebo‐controlled study to evaluate different dose‐escalation regimens

Abstract

Aim

To assess the efficacy and tolerability of tirzepatide treatment using three different dose‐escalation regimens in patients with type 2 diabetes.

Materials and Methods

In this double‐blind, placebo‐controlled study, patients were randomized (1:1:1:1) to receive either once‐weekly subcutaneous tirzepatide or placebo. The tirzepatide dose groups and dose‐escalation regimens were: 12 mg (4 mg weeks 0–3; 8 mg weeks 4–7; 12 mg weeks 8–11), 15 mg‐1 (2.5 mg weeks 0–1; 5 mg weeks 2–3; 10 mg weeks 4–7; 15 mg weeks 8–11) and 15 mg‐2 (2.5 mg weeks 0–3; 7.5 mg weeks 4–7; 15 mg weeks 8–11). The primary objective was to compare tirzepatide with placebo in HbA1c change from baseline at 12 weeks.

Results

Overall, 111 patients were randomized: placebo, 26; tirzepatide 12 mg, 29; tirzepatide 15 mg‐1, 28; tirzepatide 15 mg‐2, 28. The mean age was 57.4 years, HbA1c 8.4% and body mass index 31.9 kg/m ². At week 12, absolute HbA1c change from baseline (SE) was greater in the tirzepatide treatment groups compared with placebo (placebo, +0.2% [0.21]; 12 mg, −1.7% [0.19]; 15 mg‐1, −2.0% [0.20]; 15 mg‐2, −1.8% [0.19]). The incidence of nausea was: placebo, 7.7%; 12 mg group, 24.1%; 15 mg‐1 group, 39.3%; 15 mg‐2 group, 35.7%. Three patients discontinued the treatment because of adverse events, one from each of the placebo, 12 mg and 15 mg‐1 groups.

Conclusions

Tirzepatide treatment for 12 weeks resulted in clinically significant reductions in HbA1c. This suggests that lower starting doses and smaller dose increments are associated with a more favourable side effect profile.