BACKGROUND: Elecoglipron (AZD5004) is an oral small-molecule glucagon-like peptide-1 (GLP-1) receptor agonist administered once daily without food or fluid restriction, in development for weight management in people living with obesity or overweight and type 2 diabetes. We assessed the efficacy, safety, and tolerability of elecoglipron versus placebo in participants with obesity or overweight and at least one weight-related condition without diabetes.
METHODS: In this double-blind, randomised, controlled, phase 2 dose-ranging study with a total treatment duration of 36 weeks, adult participants were recruited from medical research centres and hospitals in Australia, Canada, Germany, Japan, Taiwan, the UK, and the USA. Participants were aged 18 years or older living with obesity (BMI ≥30 kg/m) or with overweight (BMI ≥27 kg/m) with at least one weight-related condition and without type 2 diabetes. Eligible participants were randomly assigned in a 2:3:3:3:3:5 ratio to receive 5 mg, 15 mg, 50 mg, 75 mg (weekly titration), or 75 mg (every 2-week titration) of elecoglipron or matching placebo. Elecoglipron was administered as oral once-daily tablets without titration (5 mg and 15 mg) and as three different dose-titration regimens. The daily dose of 50 mg was evaluated using an every-4-weeks dose-escalation schedule, while 75 mg was assessed with weekly or every 2-week dose-escalation schedules. Participants, treating physicians, and sponsor were masked to the treatment allocation. The dual primary endpoints were percent change in bodyweight from baseline and the proportion of patients reaching at least 5% weight loss at week 26. Safety and tolerability were assessed in all participants who received at least one dose of study treatment. This trial is registered at ClinicalTrials.gov (NCT06579092) and is completed. 2 2
FINDINGS: From Oct 8, 2024, to Feb 18, 2025, 472 individuals were screened for potential study inclusion, 162 did not meet the inclusion criteria, and 310 participants were randomly assigned to the varied elecoglipron groups or placebo. 288 participants (93%) completed the study and 231 (75%) completed the assigned treatment. The mean age of participants was 48·4 years (SD 13·7), 225 (73%) were female, 85 (27%) were male, their mean bodyweight was 106·9 kg (SD 24·1), and their mean BMI was 38·2 kg/m(SD 7·2). At week 26, the estimated mean change from baseline in bodyweight was between -2·6% (5 mg elecoglipron), and -10·5% (75 mg with weekly titration steps) compared with -0·6% with placebo. The estimated proportion of participants reaching weight reductions of at least 5% at week 26 was 40·4-88·8% with elecoglipron versus 15·6% with placebo. Adverse events were reported by 84% (27 of 32) to 98% (48 of 49) of participants across elecoglipron doses compared with 84% (68 of 81) in the placebo group, the most common being nausea, constipation, diarrhoea, headache, and vomiting. 2
INTERPRETATION: Daily oral elecoglipron demonstrated clinically meaningful weight reductions and a safety and tolerability profile consistent with the GLP-1 receptor agonist class in this phase 2 dose-ranging study, supporting phase 3 investigation in people living with obesity or overweight.
FUNDING: AstraZeneca.
