Metsera has reached a significant milestone this year with its experimental weight loss drug MET-233i. This ultra-long-acting amylin injection demonstrated an average weight loss of 8.4% over 36 weeks in a Phase I study. The news caused Metsera’s shares to rise as much as 20% on Monday morning.
Analysts had eagerly awaited these early results. In a February 25 note, Guggenheim Partners called the data from MET-233i one of Metsera’s “critical program milestones” for 2025. They added that this readout could “substantially reduce the risk” for the drug’s future development.
MET-233i is unique as the only once-monthly amylin injection currently in clinical trials. Guggenheim noted that it could be combined with Metsera’s other drugs targeting GIP and glucagon pathways. This combination could lead to new, differentiated products and help the company target different market segments.
The market for ultra-long-acting injectable incretin therapies, which includes drugs like MET-233i, is estimated by Guggenheim to reach $19 billion by 2035.
The Phase I study tested MET-233i alone in 80 overweight or obese patients without type 2 diabetes. At 36 weeks, those receiving a 1.2-mg dose lost on average 8.4% of their body weight compared to placebo. Some patients lost as much as 10.2%.
Pharmacokinetic data showed the drug’s half-life is about 19 days, supporting a once-monthly dosing schedule. Patients maintained weight loss for over four weeks after dosing, highlighting the drug’s long-lasting effect.
In terms of safety, MET-233i showed a favorable profile. There were no severe or serious side effects. Mild gastrointestinal symptoms, typical for amylin drugs but less frequent than with GLP-1 therapies, mostly appeared only during the first week of treatment. Metsera said this suggests patients quickly develop tolerance to the side effects.
Metsera plans to continue testing MET-233i as a standalone treatment, with topline results expected later this year. The company is also studying MET-233i combined with its long-acting GLP-1 drug, MET-097i. Data from this combination trial could come by late 2025 or early 2026. Additionally, data from monthly dosing of MET-097i alone is expected soon and is seen as a key milestone.
Why Amylin Therapies Matter in Weight Loss
MET-233i is an injectable form of amylin, a hormone produced by the pancreas. It works alongside insulin to slow stomach emptying and lower blood sugar levels. Unlike GLP-1 drugs, which are more common, amylin therapies may offer better tolerability and cause less loss of lean body mass.
Because of these potential benefits, many biopharma companies are developing amylin-based obesity treatments. Leading the field is Novo Nordisk, which is working on CagriSema—a combination of its popular GLP-1 drug semaglutide with an amylin analog called cagrilintide.
However, CagriSema’s results have been mixed. In December 2024, its Phase III REDEFINE 1 study showed weight loss of 22.7% at 68 weeks, which was below expectations of 25%. This led to a sharp drop in Novo Nordisk’s stock, wiping about $72 billion off its market value.
Further data released in March also disappointed investors, causing a 7% decline in the company’s share price.
Guggenheim analysts reviewed these outcomes and pointed to the study’s flexible dosing as a problem. Only 56% of patients reached the maximum dose, which they described as an “unforced error.” This likely caused the study to underestimate CagriSema’s full potential.
Despite this, Guggenheim said Novo Nordisk confirmed that amylin is a valid target for obesity treatment. The analysts believe this mistake creates an opportunity for competitors like Metsera with differentiated drugs such as the ultra-long-acting MET-233i.
Other companies also developing amylin drugs include Eli Lilly, which expects Phase II data for eloralintide by mid-2025, and AbbVie, which entered the space in March with a potential $2.2 billion deal with Danish biotech Gubra.
