GLP3 Studies: Annotated Research Bibliography

The foundational GLP3 study. This discovery and translational paper characterizes LY3437943 (retatrutide) as a single peptide engineered for balanced agonism at the glucagon, GIP, and GLP-1 receptors. Across preclinical models and first-in-human dosing it reported dose-dependent reductions in body weight and glucose, establishing proof of concept for a weekly-dosing molecule. Evidence quality: mixed preclinical-plus-early-clinical; this is the canonical reference for the compound's identity and design rationale and the natural starting point for any GLP3 literature review (PMID 35985340).

Cryo-EM structural work resolving how a single retatrutide molecule binds and activates the GLP-1, GIP, and glucagon receptors. It provides the structural basis for the balanced triple agonism described in the discovery paper, making it a key reference for researchers studying receptor-binding mechanism or designing structure-function experiments. Evidence quality: structural/biophysical — definitive for molecular mechanism, silent on physiology (PMID 39019866).

A clinical pharmacodynamic study reporting that retatrutide delayed gastric emptying in study participants, an effect consistent with GLP-1 receptor engagement and proposed as one contributor to reduced energy intake. Evidence quality: human pharmacodynamic measurement; useful as mechanistic context linking receptor activity to a measurable physiological readout (PMID 37311727).

A phase 1b, multicentre, double-blind, placebo-controlled, randomized multiple-ascending-dose trial in people with type 2 diabetes. In clinical trials the compound was studied with a safety and tolerability profile dominated by mild-to-moderate gastrointestinal events, alongside dose-dependent changes in glycemic parameters and body weight. Evidence quality: early-phase clinical (small, dose-finding); establishes tolerability and pharmacology rather than efficacy (PMID 36354040).

A 48-week randomized, placebo-controlled phase 2 trial in adults with obesity. In this clinical trial the compound was studied for body-weight change, with the most common adverse events being dose-related gastrointestinal events. Evidence quality: phase 2 randomized controlled trial — among the strongest clinical evidence in the GLP3 literature for the compound's measured effects in people (PMID 37366315).

A randomized, double-blind, placebo- and active-controlled, parallel-group phase 2 trial in adults with type 2 diabetes. The compound was studied for changes in HbA1c and body weight in a dose-dependent manner, with a safety profile consistent with the incretin class and gastrointestinal events most frequently reported. Evidence quality: phase 2 randomized controlled trial with an active comparator, strengthening interpretability (PMID 37385280).

A phase 2a substudy in participants with metabolic dysfunction-associated steatotic liver disease (MASLD). The compound was studied for change in liver fat content, with large relative reductions reported alongside body-weight change over the treatment period. Evidence quality: phase 2a substudy — informative but smaller and more exploratory than the primary phase 2 trials, and specific to a defined research population (PMID 38858523).

A preclinical study in obesity-associated tumor models reporting that retatrutide treatment was associated with reduced tumor engraftment and tumor volume relative to controls, alongside its metabolic effects. Evidence quality: preclinical/animal — exploratory and hypothesis-generating only; does not transfer to clinical conclusions and is included to map the breadth of active GLP3 research directions (PMID 40094000).

A systematic review and meta-analysis pooling randomized controlled trials of retatrutide. Across trials the compound was associated with reductions in body weight, BMI, waist circumference, fasting plasma glucose, and HbA1c versus comparators, with no statistically significant overall difference in total adverse events versus placebo (reported relative risk approximately 1.11). Evidence quality: highest clinical tier (synthesis of randomized trials), though constrained by the limited number and short duration of the underlying studies (PMID 40291085).