Scientists Behind GLP-1 Obesity Drugs Propose Dropping GLP-1 as Target

Researchers Richard DiMarchi and Matthias Tschöp, whose work led to obesity drugs like Eli Lilly's Zepbound, now propose that targeting the GLP-1 hormone may be unnecessary for weight loss treatment. Their experimental drug activating only GIP and glucagon receptors showed comparable weight loss to GLP-1-targeting drugs in rodent and monkey studies, while potentially avoiding side effects like nausea and vomiting. The hypothesis, published in a peer-reviewed draft paper, emerges as Eli Lilly's weight loss pill Foundayo received FDA approval on April 1, 2026, with clinical trial results released April 17 showing cardiovascular benefits in overweight type 2 diabetes patients. The FDA required additional testing for cardiovascular and liver safety risks, as Foundayo competes with Novo Nordisk's Wegovy in the weight loss market.

Scientists Propose GLP-1-Free Obesity Drug Approach

• ▪Richard DiMarchi and Matthias Tschöp propose that a GIP and glucagon receptor-activating molecule may result in weight loss comparable to drugs that include GLP-1 as a target, based on rodent and monkey studies
• ▪Richard DiMarchi and Matthias Tschöp propose that a GIP and glucagon receptor-activating molecule may avoid tolerability issues like nausea and vomiting that often come with approved GLP-1-targeting treatments
• ▪Richard DiMarchi and Matthias Tschöp led a group of researchers that created an experimental drug activating receptors of the GIP and glucagon hormones
• ▪Richard DiMarchi and Matthias Tschöp's work spurred the development of powerful obesity drugs like Eli Lilly's Zepbound

Eli Lilly's Foundayo Safety and Cardiovascular Trial Results

• ▪The U.S. Food and Drug Administration required Eli Lilly to conduct additional testing to assess the risks of cardiovascular events and drug-induced liver injury for Foundayo
• ▪Eli Lilly's Foundayo is in a competitive battle with Novo Nordisk's Wegovy weight loss pill
• ▪The U.S. Food and Drug Administration approved Eli Lilly's Foundayo on April 1, 2026
• ▪Eli Lilly stated there was no liver safety signal in the Foundayo clinical trial study
• ▪Eli Lilly's Foundayo reduced the risk of heart attacks and other cardiovascular problems in overweight patients with type 2 diabetes at increased risk of heart disease, compared with a common treatment
• ▪Novo Nordisk launched the Wegovy weight loss pill in 2026
• ▪Eli Lilly released results of a clinical trial for its weight loss pill Foundayo on April 17, 2026

Perspective of Richard DiMarchi and Matthias Tschöp

• ▪Richard DiMarchi and Matthias Tschöp believe their GIP and glucagon receptor approach could offer better tolerability than current GLP-1-based obesity treatments
• ▪Richard DiMarchi and Matthias Tschöp's hypothesis challenges the current paradigm that GLP-1 targeting is essential for effective obesity medications

Perspective of Eli Lilly

• ▪Eli Lilly faces competitive pressure from Novo Nordisk in the weight loss pill market with Foundayo competing against Wegovy
• ▪Eli Lilly’s Foundayo showed cardiovascular safety in overweight or obese adults with type 2 diabetes who were at increased risk of cardiovascular events.