Tirzepatide SURPASS-2 delivers superior HbA1c and weight reductions vs semaglutide 1 mg

What was reported

Tirzepatide SURPASS-2 delivers superior HbA1c and weight reductions vs semaglutide 1 mg — a Clinical trial registry and NEJM publication readout reported by Eli Lilly and Company on Aug 5, 2021. Linked to trial NCT03954834.

Related entities

Assets

Tirzepatide

Companies

Eli Lilly

Design

Open-label phase 3 head-to-head of tirzepatide 5/10/15 mg vs semaglutide 1 mg over 40 weeks.

Primary endpoint

Change in HbA1c from baseline

Result

HbA1c reductions of 2.01-2.30% and weight loss of 7.6-11.2 kg across tirzepatide doses.

Missing data

Low discontinuation; primary estimand included trial product and treatment policy estimands.

Caveats

Open-label design may bias patient-reported outcomes; not powered for MACE.

Comparison

Results exceeded prior phase 2 signals and supported both Mounjaro and Zepbound labels.

Pipeline changes

Accelerated phase 3 obesity program (SURMOUNT) and cardiovascular outcomes trials.

Unknowns

Long-term MACE benefit not established by SURPASS-2.

Comparator

Semaglutide 1 mg once weekly

Effect size

Tirzepatide 15 mg achieved -2.30% HbA1c vs -1.86% for semaglutide 1 mg.

Discontinuations

Discontinuation rates were 15-26% across arms, mostly due to adverse events.

Adverse events

Gastrointestinal events were the most common, dose-related adverse events.