LY3437943, a novel triple glucagon, GIP, and GLP-1 receptor agonist for glycemic control and weight loss: From discovery to clinical proof of concept.
Level 4 - case-series / case-control
Phase 1 single ascending dose clinical study combined with preclinical animal and in vitro models.
PubMed 35985340 · doi:10.1016/j.cmet.2022.07.013
What was done
Researchers evaluated LY3437943, a novel triple agonist at the glucagon (GCGR), glucose-dependent insulinotropic polypeptide (GIPR), and glucagon-like peptide-1 (GLP-1R) receptors. The compound was characterized in vitro for receptor activity, tested in obese mice for effects on body weight, energy expenditure, and glycemic control, and evaluated in humans in a Phase 1 single ascending dose study for safety, tolerability, pharmacokinetics, and weight reduction.
What was found
The abstract reports no exact numeric values or sample sizes. In vitro, LY3437943 showed balanced GCGR and GLP-1R activity with greater GIPR potency. In obese mice, it decreased body weight and improved glycemic control via combined calorie intake reduction and GCGR-driven energy expenditure. In the human Phase 1 single ascending dose study, safety and tolerability were reported as similar to other incretins, pharmacokinetics supported once-weekly administration, and weight reduction persisted up to day 43 after a single dose.
Why it matters
It provides proof of concept that combining glucagon-mediated energy expenditure with GIP- and GLP-1-driven appetite suppression in a single molecule produces sustained weight loss and viable pharmacokinetics in humans.
Limits
The abstract provides no sample size, demographic data, or quantitative endpoints (such as exact weight loss percentages or adverse event rates). Human data are limited to a single ascending dose Phase 1 design, which cannot establish multi-dose efficacy, long-term safety, or glycemic durability.