Summary: In this first-in-human phase I trial, 95 otherwise healthy men with overweight or obesity (BMI 25.0 to 34.9) received single ascending doses of the neuropeptide Y receptor type 2 (NPY2R) agonist BI 1820237, with or without low-dose liraglutide. Drug-related adverse events, mainly gastrointestinal, occurred in 39.0% (parts 1 and 2) and 30.6% (part 3), and effects on gastric emptying appeared additive when BI 1820237 was combined with liraglutide. This was a safety, tolerability, and pharmacokinetic study, not a weight-loss efficacy trial.
PICO Summary
| Element | Detail |
|---|---|
| Population | 95 otherwise healthy men with overweight or obesity (BMI 25.0 to 34.9 kg/m2); first-in-human, three-part, partially blinded phase I single-ascending-dose RCT (NCT04903509); conducted in Germany. |
| Intervention | Single ascending doses of the peptidic NPY2R agonist BI 1820237 (part 1: 0.075 to 2.4 mg; part 2: 1.2 mg; part 3: 0.025 to 1.2 mg plus liraglutide 0.6 mg). |
| Comparison | Placebo (parts 1 and 2), and placebo plus liraglutide 0.6 mg (part 3). |
| Outcome | Primary endpoint, proportion with drug-related adverse events: 39.0% (n=23) in parts 1 and 2 and 30.6% (n=11) in part 3, mostly gastrointestinal; one drug-related event (11.1%) occurred in a placebo-plus-liraglutide participant. Transient nausea and vomiting were seen at higher doses. Post-dose paracetamol pharmacokinetics suggested additive effects of BI 1820237 and low-dose liraglutide on gastric emptying. No formal between-group significance testing or weight-loss efficacy outcome was reported in the abstract; no 95% CI, p value, or ARR/NNT is applicable to this exploratory PK and PD design. |
Expert Commentary
This report should be read as an early safety and pharmacology signal, not as evidence of efficacy. The verdict is that BI 1820237 was tolerated at lower single doses, that gastrointestinal adverse events accumulated at higher doses, and that its slowing of gastric emptying appeared additive to low-dose liraglutide on a paracetamol absorption marker. No weight change was demonstrated, and the abstract reports no formal hypothesis testing, so the additive signal is descriptive and hypothesis-generating only. The dominant limitation is the design itself: single ascending doses in 95 healthy men over a short window cannot speak to sustained weight loss, durability, or safety with repeated dosing, and the all-male, narrow-BMI sample limits generalisability to women and to higher-BMI patients who most need new options. The trial was funded and conducted by the manufacturer, and the partially blinded structure warrants caution when weighing tolerability claims. Can I use this with my patients? Not yet; BI 1820237 is an investigational compound with no efficacy or repeat-dose safety data, and it is unsuitable for any clinical use today. What is needed now is a multiple-ascending-dose programme with objective weight and body-composition endpoints, balanced enrolment, and head-to-head tolerability against established incretin therapy before the additive-mechanism hypothesis can be taken seriously.
References
Beetz N, Kalsch B, Forst T, Schmid B, Schultz A, Hennige AM. A randomized phase I study of BI 1820237, a novel neuropeptide Y receptor type 2 agonist, alone or in combination with low-dose liraglutide in otherwise healthy men with overweight or obesity. Diabetes Obes Metab. 2025;27(1):71-80. doi:10.1111/dom.15984
