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Experimental Add-On Drug Boosted Weight Loss In Diabetes Patients On Dulaglutide

A new injectable being tested alongside a GLP-1 diabetes drug added measurable weight loss in a small early human trial, according to findings published in Molecular Metabolism.

By Dr. Axe Editorial Team · October 9, 2026 · 1 source · Watch

An experimental once-weekly injectable called nisotirostide added up to 2.58 kg of extra weight loss when combined with the diabetes drug dulaglutide, according to a Phase 1 study published October 3, 2026, in Molecular Metabolism.

Researchers tested nisotirostide, a new drug that activates the NPY2 receptor, a hormone-signaling target different from the GLP-1 receptor used by drugs like semaglutide and dulaglutide. In mouse studies, nisotirostide alone reduced body weight by up to 12%; combined with a GLP-1 drug, mice lost up to 31% of body weight, which the study authors describe as a synergistic effect. The Phase 1 human trial enrolled 65 healthy participants and participants with type 2 diabetes already taking a 1.5 mg weekly dose of dulaglutide. Participants received a single injection of nisotirostide at doses ranging from 0.025 mg to 1 mg. At the 1 mg dose, nisotirostide alone reduced body weight by 0.75 kg versus placebo, a difference the study did not report as statistically meaningful. When added to dulaglutide, nisotirostide produced up to 2.58 kg more weight loss than dulaglutide alone, which did reach statistical significance. The drug's pharmacokinetics, how the body absorbs and clears it, supported once-weekly dosing. Gastrointestinal side effects, including nausea and vomiting, were the most commonly reported adverse events, and the study authors note these were dose-dependent and mild to moderate in severity.

The study authors report that in mice, nisotirostide improved blood sugar control independent of weight loss, suggesting the NPY2 pathway affects glucose metabolism through a route separate from calorie restriction. NPY2 is a receptor normally activated by a gut hormone involved in appetite regulation; drugs that target it are designed to suppress appetite through a different signal than the GLP-1 pathway, which is why researchers are testing it as an add-on rather than a replacement.

Extra weight loss when added to dulaglutide

Molecular Metabolism, 2026, Briere et al.

This single-dose Phase 1 study in 65 people measures safety and early pharmacology, not long-term weight loss or diabetes outcomes, and the solo-drug weight result was not statistically significant. Thirteen of the authors are employees and stockholders of Eli Lilly and Company.

Dr. Axe’s Take

This drug is investigational, not available to prescribe, so there is nothing to act on yet. What interests me is a second appetite pathway being tested alongside GLP-1 drugs rather than just raising the GLP-1 dose. My position on the approved GLP-1 class is this: I pair these medicines with a whole-food diet, high protein, fiber and resistance training, since the class does not address muscle loss on its own. Many people do well on a much lower dose, often 10 to 20% of the labeled dose, worked out with the prescribing doctor instead of adjusting on their own. Watch for nausea and vomiting, the most common side effects this study flags.

— Dr. Axe

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Study summary

Who: 65 participants in Phase 1: healthy adults and adults with type 2 diabetes already taking 1.5 mg weekly dulaglutide
Design: Phase 1 human trial with single subcutaneous doses of nisotirostide (0.025 to 1 mg), alongside separate mouse studies; ClinicalTrials registry NCT04641312
Dose: Single injection doses from 0.025 mg to 1 mg; mouse studies tested monotherapy and combination with a GLP-1 drug
Primary result: At 1 mg, nisotirostide alone reduced body weight by 0.75 kg versus placebo (not statistically significant); combined with dulaglutide, up to 2.58 kg more weight loss versus dulaglutide alone (statistically significant)
Secondary: In mice, nisotirostide alone reduced body weight by up to 12%; combined with a GLP-1 drug, up to 31% weight loss. Mice also showed improved glucose control independent of weight loss. Pharmacokinetics supported once-weekly human dosing.
Funding / conflicts: Funder listed in the journal record: Eli Lilly and Company. Conflicts declared in the PubMed record: Daniel A Briere, Jennifer K Leohr, Helle Linnebjerg, Avinash Muppidi, Meghan Antonellis, Patrick Antonellis, Todd M Suter, Elizabeth Smith LaBell, Daniel Lopes, Mridula Dogra, Tamer Coskun, Jorge Alsina-Fernandez, and Kieren James Mather are employees and stockholders of Eli Lilly and Company, Indianapolis, USA.
Date: Oct 3, 2026