What question did this study set out to answer?

This research aims to evaluate the safety and pharmacokinetics of AT7687 as a treatment for obesity.

June 9, 2026

1228-OR: First-in-Human Study Demonstrates GIP Receptor (GIPR) Antagonist AT7687 as Well-Tolerated and Suitable for Once-Weekly Subcutaneous Injection for Treatment in People Living with Obesity

Key Points

This research aims to evaluate the safety and pharmacokinetics of AT7687 as a treatment for obesity.
Randomized, double-blind, placebo-controlled study design.
60 participants in single ascending dose (SAD) and 42 in multiple ascending dose (MAD) cohorts received either AT7687 or placebo.
Assessment included treatment-emergent adverse events (TEAEs) and pharmacokinetic parameters.
AT7687 was well-tolerated with 46% experiencing mild TEAEs compared to 39% in placebo.
Statistically significant improvement in insulinogenic index in both SAD (p=0.009) and MAD (p=0.029).
No significant weight changes were observed, but LDL-C reduction averaged -9.1% at Day 29.

Abstract

Introduction and Objective: AT7687 is a first-in-class peptide GIPR antagonist validated as anti-obesity therapy in obese monkeys, as monotherapy and in combination with liraglutide and cagrilintide. This randomized, double-blind, placebo-controlled study evaluated the safety, pharmacokinetics (PK), and pharmacodynamics of AT7687 (AT). Methods: In the single ascending dose (SAD) part, 60 participants randomized 6:2 by cohort received a single dose of AT (range: 12.5 mg - 380 mg) or placebo (PL). In the multiple ascending dose (MAD) part, 42 participants randomized 10:2 by cohort received 4 doses of AT (range: 17 mg - 150 mg) or PL once weekly. BMI range was 20·0−39·9 kg/m². The primary endpoint was treatment-emergent adverse events (TEAEs); secondary endpoints were PK parameters; exploratory endpoints included changes in oral glucose tolerance test (OGTT) response, body weight, lipids and hemodynamics. Results: All doses were safe and well-tolerated. 36/79 (46%) subjects on AT and 9/23 subjects (39%) on PL experienced only mild TEAEs; moderate TEAEs occurred in 7/79 (9%) and 0/23 subjects (0%), respectively. There were no severe or serious AEs and no discontinuations. Gastrointestinal AEs were mild and occurred in similar proportions (19% AT; 17% PL). Cmax and AUC exposure were dose proportional. AT led to statistically significant change in post- minus pre-dose Insulinogenic Index in both SAD (p=0.009) and MAD (p=0.029), with no difference in PL. In MAD, the placebo-adjusted mean change in LDL-C was up to -9.1% at Day 29 and up to 5.3 bpm reduction in resting heart rate at Day 22. There were no significant changes in weight at Day 29. Conclusion: AT7687 was well-tolerated, showed clinical evidence of potent GIPR antagonism, and encouraging trends of cardiometabolic benefits, justifying advancement into longer trials to assess its efficacy as monotherapy and as an ideal combination partner in obesity management. Disclosure A. Baladi Nejad: Employee; Current; Antag Therapeutics. Employee; Ended; Novo Nordisk A/S. J. Boland: None. A.H. Hand: None. K.M. Knudsen: Consultant; Current; Antag Therapeutics, Breye Therapeutics. L.S. Gasbjerg: Stock/Shareholder; Current; Antag Therapeutics. Consultant; Current; Antag Therapeutics. Advisory Panel; Ended; Novo Nordisk. Other - Speaker honorarium; Ended; Novo Nordisk. A.H. Sparre-Ulrich: None. R. Nkulikiyinka: Employee; Current; Antag Therapeutics.

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1228-OR: First-in-Human Study Demonstrates GIP Receptor (GIPR) Antagonist AT7687 as Well-Tolerated and Suitable for Once-Weekly Subcutaneous Injection for Treatment in People Living with Obesity

Key Points

Abstract

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