In a phase 3 trial of patients with obesity and type 2 diabetes, the dual-action agonist tirzepatide administered once weekly enabled about 80% of participants to achieve “substantial and clinically meaningful reduction in bodyweight,” researchers report. Its “safety profile was similar to other incretin-based therapies for weight management,” the authors conclude. Tirzepatide is a glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist.
Conducted in 7 countries, the trial included adults with BMIs of 27 or higher and glycated hemoglobin (HbA1c) of 7% to 10%. Randomized to once-weekly, subcutaneous tirzepatide 10 mg or 15 mg or placebo, the participants had these outcomes based on coprimary endpoints of the percent change in bodyweight from baseline and bodyweight reduction of 5% or higher.
“Between March 29, 2021, and April 10, 2023, of 1,514 adults assessed for eligibility, 938 (mean age 54.2 years [SD 10.6], 476 [51%] were female, 710 [76%] were White, and 561 [60%] were Hispanic or Latino) were randomly assigned and received at least one dose of tirzepatide 10 mg (n = 312), tirzepatide 15 mg (n = 311), or placebo (n = 315). Baseline mean bodyweight was 100.7 kg (SD 21.1), BMI 36.1 kg/m2 (SD 6.6), and HbA1c 8.02% (SD 0.89; 64.1 mmol/mol [SD 9.7]). Least-squares mean change in bodyweight at week 72 with tirzepatide 10 mg and 15 mg was –12.8% (SE 0.6) and –14.7% (0.5), respectively, and –3.2% (0.5) with placebo, resulting in estimated treatment differences versus placebo of –9.6% percentage points (95% CI –11.1 to –8.1) with tirzepatide 10 mg and –11.6% percentage points (–13.0 to –10.1) with tirzepatide 15 mg (all P <0.0001). More participants treated with tirzepatide versus placebo met bodyweight reduction thresholds of 5% or higher (79–83% vs 32%). The most frequent adverse events with tirzepatide were gastrointestinal-related, including nausea, diarrhoea, and vomiting and were mostly mild to moderate in severity, with few events leading to treatment discontinuation (<5%). Serious adverse events were reported by 68 (7%) participants overall and two deaths occurred in the tirzepatide 10 mg group, but deaths were not considered to be related to the study treatment by the investigator.”