ADA 2022 – Lilly’s triple-G is one to watch

Mounjaro might be the name on everyone’s lips following impressive recent results in obesity with the GIP/GLP-1, but a much earlier Lilly asset, LY3437943, is also worth keeping an eye on. The project is a so-called triple-G – an agonist of GIP, GLP-1 and glucagon receptors – and data from a phase 1 trial, presented at ADA yesterday, are encouraging. Though primarily a safety study of ascending weekly doses in a type 2 diabetes population, the study also measured blood sugar and weight. After three months’ treatment, mean HbA1c decreased from baseline in all groups, with higher doses of LY3437943 showing statistically significant placebo-adjusted decreases of up to 1.56%. The agent also prompted dose-dependent decreases in mean placebo-adjusted body weight of up to 8.96kg, and safety seemed acceptable, with the most common treatment-emergent adverse events being nausea and diarrhoea, which were mostly mild. The lack of a dose response on the HbA1c endpoint is perhaps puzzling, though patients numbers were small, with only nine to 12 subjects in each LY3437943 arm. Data from two larger phase 2 trials in diabetes and obesity could come this year, and might clarify the situation.

Data from Lilly's phase 1 triple-G trial (NCT04143802)
Agent LY3437943 LY3437943 LY3437943 Trulicity Placebo
Dose 3mg 3/6mg 3/6/9/12mg 1.5mg -
Change from baseline in HbA1c at 12wk (%) -1.7 -1.9 -1.59 -0.96 -0.34
Change from baseline in body weight at 12wk (kg) -4.39 -7.52 -8.65 +0.39 +0.31
Source: Lilly presentation. 

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