Lilly's tirzepatide beats Novo's semaglutide in diabetes phase 3, but another study muddies picture

Another phase 3 clinical trial of Eli Lilly’s tirzepatide in Type 2 diabetics has met its primary endpoint. The dual GIP/GLP-1 agonist beat Novo Nordisk’s semaglutide against multiple measures, although recent data on another dose of the rival drug suggest Lilly has a fight on its hands.

In recent months, Lilly has released data from a series of late-phase trials that have linked tirzepatide to significant reductions in participants’ blood sugar and body weight. The latest readout, from the 1,879-subject, 40-week SURPASS-2 clinical trial, provides evidence that tirzepatide is more effective than the 1-mg dose of Novo’s semaglutide.

Across three tirzepatide doses, Lilly saw reductions in A1C, a measure of blood sugar, ranging from 2.09% to 2.46%. A1C at baseline was 8.28%. Participants on 1 mg of semaglutide experienced a drop of 1.86% in A1C.

The pattern of dose-dependent tirzepatide results, all of which beat semaglutide, was seen across the other endpoints. The proportion of patients with A1C of 5.7% or below, the threshold of normal, in the tirzepatide arms ranged from 29.3% to 50.9%, compared to 19.7% in the semaglutide cohort.

Analysts praised the data. The team at Evercore said the data look very good, while analysts at Jefferies said the competitive pressure on Novo is set to rise.

Lilly also linked tirzepatide to significant reductions in body weight. Participants on the highest, 15-mg dose of tirzepatide lost 12.4 kg, which works out to a 13.1% decline from baseline. Subjects on semaglutide lost 6.2 kg.

The weight endpoint is a clear win for tirzepatide over 1 mg of semaglutide. However, Novo recently linked once-weekly dosing with 2.4 mg of semaglutide to a 14.9% reduction in body weight by Week 68. The Novo trial tracked patients for longer, and cross-trial comparisons can be unreliable, but the available data suggest the higher dose of semaglutide may provide a tougher test for tirzepatide.

Semaglutide appears to have a tolerability edge over tirzepatide, too. In the tirzepatide arms, 5.1% to 7.9% of participants stopped treatment due to adverse events. The dropout rate in the semaglutide cohort was 3.8%. Lilly sees value in all three doses of tirzepatide. Some patients could stick to a lower dose to sacrifice some efficacy to manage tolerability while others escalate to 10 mg and 15 mg. 

More data on tirzepatide are coming. Lilly has delivered top-line results from four of its seven phase 3 tirzepatide trials in recent months. The ongoing studies include a mammoth study Lilly initiated last year to assess the effect of tirzepatide on cardiovascular outcomes in patients with Type 2 diabetes.