EASD 2022: A Novel Triple GIP/GLP-1/Glucagon Receptor Agonist, Provides Glucose Lowering and Weight Loss in Patients with Type 2 Diabetes After 12 Weeks of Treatment
In the management of various metabolic disorders, there is a development of many multi-receptor incretin agonists. Ly3437943(LY): A novel triple agonist which is under clinical trials for its potential action on glucose dependent insulinotropic polypeptide (GIP), glucagon-like polypeptide-1 (GLP-1), and glucagon receptors.
In order to study the above, a randomized, double-blind, placebo-controlled, Phase 1 proof-of-concept study was undertaken to determine the safety, efficacy and tolerability of multiple ascending doses of LY in patients with type 2 diabetes (T2D). After randomizing 72 patients (9:3:1) to 5 rising dose cohorts of subcutaneous LY, placebo, and dulaglutide 1.5mg respectively, the drug efficacy was monitored by the change in HbA1c and change in body weight at 12 weeks. Mean HbA1c decreased from baseline in all groups, but higher doses of the LY showed a statistically significant, placebo -adjusted reduction of HbA1c from baseline by 17.1 mmol/mol. By week 12, there was a reduction in the mean systolic and diastolic blood pressure from baseline in the LY group as compared to placebo. In most of the LY and dulaglutide cohorts, an increase in pulse and heart rate from baseline was observed.Except at the initial cohort, dose-dependent decreases in mean placebo-adjusted body weight of up to 8.96 kg were observed with LY. This investigation revealed treatment-emergent gastric adverse events which were of mild form.
In conclusion, LY exhibited a similar safety and tolerability to other incretins with a significant reduction in HbA1c suggesting LY to be a promising alternative in the diabetes armamentarium having additional benefits for patients with T2D and obesity vs existing therapies.
Abstract 111, European Association for the Study of Diabetes (EASD) International Congress 2022, 19th – 23rd Sept. 2022, Stockholm
