GLP-1 medications, such as Ozempic and Wegovy, are known to cause side effects such as nausea, vomiting, and diarrhea.
According to research from 2025, 42 out of 288 people with overweight or obesity taking GLP-1 medication (14.6%) quit the treatment due to an inability to tolerate side effects.
Finding alternatives to GLP-1 drugs could help some people follow the weight loss treatment with fewer side effects. A new study published in September 2026 has explored the investigational, or experimental, drug petrelintide to determine whether it could support weight loss with fewer gastrointestinal side effects.
In a combined comment, study authors Sten Madsbad and Jens Holst explain that “[t]he therapeutic landscape of obesity is changing rapidly, most recently with long-acting amylin agonists as a novel class of anti-obesity medications. Amylin is co-secreted with insulin from pancreatic β cells in response to nutrient intake; it slows gastric emptying, suppresses postprandial glucagon secretion, and probably acts as a satiety signal.”
They add that, “[i]mportantly, these effects are mediated through pathways partly complementary to those of GLP-1,” and that “the relatively favorable tolerability [per the study findings] supports the potential of amylin agonists as monotherapy.
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However, while initial findings, including clinically meaningful weight reductions, are promising, further research is necessary before petrelintide becomes an available weight loss treatment.
Participants in the study experienced an up to 9.8% change in body weight after 28 weeks.
The phase 2 trial involved 485 participants with either overweight or obesity and no history of diabetes. Participants received either the placebo or different doses of petrelintide:
The mean percentage change in body weight ranged from 7.9% in those taking 1 mg petrelintide for 28 weeks to 9.8% in those taking 5 mg.
Medical News Todayspoke with Clare Thompson, MBBS, BSc, nMRCGP, DCH, DRCOG, LMCC, general practitioner at the Cadogan Clinic, to find out more about these findings.
“Losing an 8% to 10% average of weight over a 28-week period is a significant and positive outcome for patients taking amylin.”
The researchers found that those taking petrelintide experienced “similar gastrointestinal tolerability” to individuals in the placebo group.
Individuals did experience mild nausea when increasing the dose. In the combined comment, Madsbad and Holst explained the following:
“The most common gastrointestinal adverse event was nausea (20% vs 6% with placebo), whereas vomiting, diarrhea, and constipation occurred at frequencies similar to those with placebo. Gastrointestinal events were mild to moderate and occurred mainly during dose escalation.”
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They added that “[o]nly six of 404 participants discontinued petrelintide because of gastrointestinal adverse events.”
Thompson told MNTthat “[a]mylin and GLP-1 medications both cause delayed gastric emptying, which naturally results in a degree of nausea. In GLP-1 patients, nausea tends to wear off over time due to metabolic adaptation to the product.”
She explained that she would “expect to see a similar mechanism with amylin, as well as patients’ tolerability improving over time with each dose change.”
The trial suggests that petrelintide could be beneficial for weight management, with early findings showing notable weight loss and mild side effects.
However, it is not currently available commercially.
MNTasked Thompson what should follow before the medication might be available for patients.
She said that, while petrelintide “will interest patients who struggle to tolerate a GLP-1 medication because of side effects,” there needs to be “[m]ore data and a phase 3 clinical trial […] before prospective patients can make any meaningful conclusions about whether to try an amylin product instead of a GLP-1.”
The study authors also note in a comment that, “[w]hether gastrointestinal adverse effects occur in the same individuals who are intolerant of GLP-1-based therapies is also unclear.” As such, additional research to determine this would be necessary.
Thompson concluded, “This is an exciting new drug that needs more concrete data and larger studies on a bigger population, including diabetic patients, to see whether they might also gain benefit from an alternative product for HbA1c and weight control.”
