Related Experiment Video
Updated: Sep 16, 2025

Multidisciplinary Approach to Obesity Management: A Case Report
Published on: May 30, 2025
Long-acting PYY3 -36 analogue with semaglutide for obesity: from preclinical assessment through randomized clinical
Birgitte S Wulff1, Adam Paul Chambers1, Cynthia Karenina Osorto Contreras2
1Novo Nordisk A/S, Måløv, Denmark.
Objective:
The hormone peptide YY (PYY; cleaved into Y2-selective form PYY3-36) is an attractive candidate for use as a complementary pharmacotherapy for obesity along with glucagon-like peptide-1 (GLP-1) receptor agonists. This series of studies investigated a novel long-acting PYY3-36 analogue (PYY1875) alone and as an add-on to semaglutide for treatment of obesity.
Methods:
Weight loss and food intake were first investigated in obese male rats, followed by phase 1 and 2 clinical studies investigating efficacy, safety, tolerability, pharmacokinetics, and pharmacodynamics of PYY1875 as monotherapy and in combination with semaglutide in participants with overweight or obesity.
Results:
PYY1875 induced additional body weight loss in semaglutide-treated obese rats. In the phase 1 study, all doses of PYY1875 alone and coadministered with semaglutide were tolerated. In the phase 2 study, a modest but not clinically meaningful treatment effect of PYY1875 1.0 mg versus placebo as an add-on to semaglutide 2.4 mg was observed. However, gastrointestinal-related adverse events were common with the 1.0-mg PYY1875 dose, and the 2.0-mg PYY1875 dose escalation regimen was not tolerated (both as add-ons to semaglutide).
Conclusions:
PYY1875 showed modest efficacy as an add-on to semaglutide for weight management in people with obesity, but the treatment was not well tolerated.
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