Obesity Drug 'Triple Agonist' Race Heats Up... Lilly Candidate Shows 2x Ozempic's Weight-Loss Effect

Lilly reports 20.9% weight loss in Phase 3 trial
Novo Nordisk and Hanmi also accelerate development of next-generation drugs

Global pharmaceutical companies are intensifying their race to develop next-generation obesity treatments with “triple agonist” action. The competition is heating up after a drug candidate from U.S.-based Eli Lilly demonstrated more than twice the weight-loss effect of Ozempic, an existing diabetes treatment. Novo Nordisk and Hanmi Pharmaceutical are also accelerating development of drugs targeting three hormone receptors.

According to the global pharmaceutical industry on October 30, Lilly announced on October 28 (local time) that retatrutide showed superior weight-loss and blood sugar control effects to Ozempic in a Phase 3 trial involving 1,298 patients with type 2 diabetes. Over 80 weeks, patients who received 12 mg of retatrutide lost an average of 20.9% of their body weight, more than twice the 9.4% recorded in the group receiving 2 mg of Ozempic. Average weight loss was 21.5 kg and 9.5 kg, respectively. The reduction in glycated hemoglobin was also greater with retatrutide, at 2.2 percentage points compared with 1.8 percentage points for Ozempic. The group receiving 9 mg of retatrutide lost 19.5% of their body weight.

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Retatrutide is a triple agonist that acts on three receptors: glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), and glucagon. While Wegovy and Ozempic act on GLP-1 and Mounjaro acts on GLP-1 and GIP, retatrutide also targets glucagon. It is designed to boost energy expenditure in addition to suppressing appetite and regulating blood sugar. In a separate Phase 3 obesity trial, Lilly previously recorded weight loss of up to 28.3% over 80 weeks. A total of 45.3% of patients lost at least 30% of their body weight. Lilly plans to submit an application for approval to the U.S. Food and Drug Administration (FDA) in the first quarter of next year.

Lilly is also developing a combination therapy targeting another hormone. The treatment, called “EloraTZP,” combines the dual agonist tirzepatide with eloralintide, an amylin receptor agonist. In a Phase 2b trial announced last month, it recorded weight loss of up to 23.3% over 48 weeks, higher than the 14.8% recorded with tirzepatide alone. In its third-quarter earnings materials released on October 29, Lilly reaffirmed its plan to begin a Phase 3 trial of EloraTZP in the fourth quarter of this year.

Competitor Novo Nordisk is developing UBT251, a GLP-1, GIP, and glucagon triple agonist licensed from China’s United Biotechnology last year. It recorded weight loss of up to 19.7% over 24 weeks in a Phase 2 trial in China, and a global Phase 1b/2a trial is also underway. Results from the global trial are expected next year.

Chinese pharmaceutical companies have also entered the race to develop triple agonists. Minwei Biotech began a Phase 3 obesity trial of MWN109 in China last month. Hengrui Pharma recorded weight loss of up to 16.0% over 12 weeks in a Phase 1 trial in China of HRS-4729 (KAI-4729), which it is co-developing with U.S.-based Kailera. A Phase 2 trial is now underway in China, while Kailera is pursuing a Phase 1 trial outside China.

In South Korea, Hanmi Pharmaceutical is conducting a Phase 2 trial of zantretide (HM15275) for obesity and diabetes in the United States. On October 23, the World Health Organization (WHO) also finalized its international nonproprietary name. Hanmi Pharmaceutical expects to complete its Phase 2 obesity trial in the first half of next year, with the goal of achieving weight loss of at least 25% while minimizing muscle loss.

This content was produced with the assistance of AI translation services.