01-11-2022 | Diabetes | News | Article
Author: Eleanor McDermid
medwireNews: A novel triple receptor agonist has demonstrated an acceptable safety profile and promising reductions in blood glucose and bodyweight in a phase 1b trial reported in The Lancet.
In common with tirzepatide, the novel medication, currently known as LY3437943, stimulates the receptors for glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide (GLP)-1, but it is also a glucagon receptor agonist.
It “is less potent at the human glucagon and GLP-1 receptors compared with native glucagon and GLP-1, and more potent at human GIP compared with native GIP,” say Zvonko Milicevi (Eli Lilly and Company, Indianapolis, Indiana, USA) and co-researchers.
In this trial, LY3437943 was tested in 72 people with type 2 diabetes, given as subcutaneous injections at doses ranging from 0.5 to 12 mg/week, and compared with dulaglutide 1.5 mg (not titrated up from 0.75 mg) and placebo.
Its safety profile was “consistent” with those of “other incretin-based therapeutic agents in early phases of development,” say the investigators, with gastrointestinal complaints being the most common adverse effect.
The medication had a half-life of approximately 6 days, making it suitable for once-weekly dosing.
Moreover, participants taking LY3437943 had an average placebo-adjusted glycated hemoglobin reduction of up to 1.6% (17.1 mmol/mol) during 12 weeks of treatment and a placebo-adjusted bodyweight reduction of up to 8.96 kg.
“The findings suggest that simultaneous agonism on these three receptors is a therapeutic approach that has acceptable safety and tolerability across a range of doses administered over 12 weeks,” concludes the team.
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Lancet 2022; doi:10.1016/S0140-6736(22)02033-5
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