Tirzepatide, a Dual GIP/GLP-1 Receptor Agonist, is Effective and Safe When Added to Basal Insulin for Treatment of Type 2 Diabetes (SURPASS-5)

Aim Tirzepatide is a novel dual GIP/GLP-1 receptor agonist in development for type 2 diabetes (T2D). Efficacy and safety of tirzepatide vs placebo was assessed in people with T2D as an add-on to titrated insulin glargine with or without metformin. Methods In this double-blind, placebo-controlled, 40-week Phase 3 study, 475 people with T2D (mean baseline age 60.6 years; T2D duration 13.3 years; HbA1c 8.31%; BMI 33.4 kg/m2) were randomized (1:1:1:1) to tirzepatide (5 mg, 10 mg, 15 mg) or placebo, as an add-on to their existing therapy. Primary efficacy measure was mean change in HbA1c from baseline at 40-week. Results All 3 tirzepatide doses (dose [LSM±SE]%; 5 mg [-2.23±0.08]%; 10 mg [-2.59±0.08]%; 15 mg [-2.59±0.08]%) were superior to placebo (-0.93±0.08)% in change from baseline in HbA1c (Difference vs placebo (95% CI) (p<0.001) : 5 mg [-1.30 {-1.52, -1.07}]%; 10 mg [-1.66 {-1.88, -1.43}]%; 15 mg [-1.65 {-1.88, -1.43}]%). Tirzepatide was generally well tolerated, and the most common adverse events were gastrointestinal (diarrhea, nausea, and vomiting) and were mild to moderate in severity. Level 2 hypoglycemia incidence (Blood glucose<54 mg/dL) did not differ between tirzepatide and placebo. Three episodes of level 3 (severe) hypoglycemia were observed (2 episodes in tirzepatide 10 mg and 1 in tirzepatide 15mg). Conclusion Tirzepatide demonstrated superior and clinically meaningful improvements in glycemic control and BW loss without increasing hypoglycemia vs placebo in patients with T2D when added to titrated basal insulin. Publication History Article published online: 26 May 2022 © 2022. Thieme. All rights reserved. Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany