Lancet (London, England)Jun 8, 2026

Elecoglipron, an oral drug activating GLP-1 receptors, tested in adults with obesity or overweight in a phase 2 clinical trial

GLP-1 Therapies Weekly Brief ↗PubMed ↗DOI ↗

Updated Jun 27, 2026

Abstract

Essence

Daily oral elecoglipron produced dose-related weight loss versus placebo in adults with obesity or overweight without diabetes.

Evidence

This multicentre, double-blind, randomised, placebo-controlled phase 2 dose-ranging trial enrolled 310 adults and assessed bodyweight change and at least 5% weight loss at week 26 across elecoglipron doses.

Caveat

The study was phase 2, lasted 36 weeks with 26-week primary endpoints, and 75% of participants completed assigned treatment, so longer-term durability and phase 3 confirmation remain outside this abstract.

Simplified

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.

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Declaration of interests MJD has acted as a consultant, advisor, and speaker for Eli Lilly, Novo Nordisk and Sanofi; as a consultant and advisor for Kailera; has attended advisory boards for AbbVie, Amgen, AstraZeneca, Biomea Fusion, Carmot Roche, Daewoong Pharmaceutical, Sanofi, Zealand Pharma, Regeneron, GSK, Innovent Bio, and EktaH; and as a speaker for AstraZeneca, Boehringer Ingelheim, and Zuellig Pharma. MJD has received grants from AstraZeneca, Boehringer Ingelheim, and Novo Nordisk. VRA has institutional contracts with Amgen, AstraZeneca, Applied Therapeutics, Biomea, Corcept, Eli Lilly, Fractyl, Kailera, Novo Nordisk, Pfizer, Recordati, Rhythm, and Servier and is a consultant for Baim, Mediflix, Roche, and Sanofi. JR reports clinical research grants from Amgen, Applied Therapeutics, AstraZeneca, Biomea Fusion, Boehringer Ingelheim, Corcept, Corxel, Eli Lilly, Hanmi, Merck, Novo Nordisk, Pfizer, Regeneron, Roche, Regor, Sanofi, Structure Therapeutics, and Terns; JR serves or has served on scientific advisory boards and received honoraria or consulting fees from Amgen, Applied Therapeutics, Arrowhead, Biomea Fusion, Boehringer Ingelheim, Corcept, Eccogene, Eli Lilly, Hanmi, i2O Therapeutics, Novo Nordisk, Regeneron, Roche, Sanofi, Structure Therapeutics, and Terns; and has received honoraria for lectures from Eli Lilly, Novo Nordisk, and Sanofi. MC has served as unpaid advisor to the National Institute of Health and Care Excellence on obesity and diabetes; is Medical Director for Lighterlife (commercial Very Low Calorie Diet provider); is Medical Advisor to McDonalds UK; has recieved research funding to perform clinical trials for AstraZeneca, Novo Nordisk, Lilly, Boehringer Ingelheim, and Amgen; honoraria for talks and advisory boards from Novo Nordisk, Lilly and Boehringer Ingelheim; and travel or subsistence costs to attend meetings or conferences from AstraZeneca, Novo Nordisk, Lilly, Boehringer Ingelheim, and Amgen. SDP has received grants for clinical trials from Novo Nordisk, AstraZeneca, Sanofi, Eli Lilly, Boehringer Ingelheim, Prometic, and Pfizer; and consulting fees from AstraZeneca, Bausch Health, Eli Lilly, Novo Nordisk, Janssen, Boehringer Ingelheim, Sanofi, Merck, Abbott, Dexcom, HLS, Bayer, AbbVie, Roche, Amgen, and Pfizer. SDP has also received payment for medical education lectures and speakers bureaus from AstraZeneca, Bausch, Eli Lilly, Novo Nordisk, Janssen, Boehringer Ingelheim, Sanofi, Merck, Abbott, Dexcom, HLS, Bayer, and Pfizer, and has received travel support from AstraZeneca, Bausch, Eli Lilly, Novo Nordisk, Beohringer Ingelheim, Abbott, and Dexcom. EM, SM, PAJ, DG, AA, EPR, and CDS are employees and stockholders of AstraZeneca.

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Elecoglipron, an oral drug activating GLP-1 receptors, tested in adults with obesity or overweight in a phase 2 clinical trial

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