Eloralintide, a selective amylin receptor agonist for the treatment of obesity: a 48-week phase 2, multicentre, double-blind, randomised, placebo-controlled trial.
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| Název: | Eloralintide, a selective amylin receptor agonist for the treatment of obesity: a 48-week phase 2, multicentre, double-blind, randomised, placebo-controlled trial. |
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| Autoři: | Billings LK; Endeavor Health (NorthShore Hospitals), Skokie, IL, USA; University of Chicago, Pritzker School of Medicine, Chicago, IL, USA. Electronic address: lbillings@northshore.org., Hsia S; Velocity Clinical Research, Huntington Park, Los Angeles County, CA, USA., Bays H; Louisville Metabolic and Atherosclerosis Research Center, Louisville, KY, USA., Tidemann-Miller B; Eli Lilly and Company, Indianapolis, IN, USA., O'Hagan J; Eli Lilly and Company, Indianapolis, IN, USA., Tham LS; Eli Lilly and Company, Indianapolis, IN, USA., Butler A; Eli Lilly and Company, Indianapolis, IN, USA., Kazda C; Eli Lilly and Company, Indianapolis, IN, USA., Mather KJ; Eli Lilly and Company, Indianapolis, IN, USA., Coskun T; Eli Lilly and Company, Indianapolis, IN, USA. |
| Zdroj: | Lancet (London, England) [Lancet] 2025 Dec 06; Vol. 406 (10520), pp. 2631-2643. Date of Electronic Publication: 2025 Nov 06. |
| Způsob vydávání: | Journal Article; Randomized Controlled Trial; Clinical Trial, Phase II; Multicenter Study |
| Jazyk: | English |
| Informace o časopise: | Publisher: Elsevier Country of Publication: England NLM ID: 2985213R Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1474-547X (Electronic) Linking ISSN: 01406736 NLM ISO Abbreviation: Lancet Subsets: MEDLINE |
| Imprint Name(s): | Publication: 2004- : London : Elsevier Original Publication: London : J. Onwhyn |
| Výrazy ze slovníku MeSH: | Obesity*/drug therapy , Anti-Obesity Agents*/administration & dosage , Anti-Obesity Agents*/adverse effects , Anti-Obesity Agents*/therapeutic use , Amylin Receptor Agonists*/administration & dosage, Humans ; Middle Aged ; Double-Blind Method ; Male ; Female ; Adult ; Aged ; Treatment Outcome ; Adolescent ; Young Adult ; Dose-Response Relationship, Drug ; Weight Loss/drug effects |
| Abstrakt: | Background: Amylin-based therapies are emerging as promising obesity medications. Eloralintide is a novel, selective amylin receptor agonist in development for weight management. We performed a phase 2, double blind, randomised, placebo-controlled trial with the aim of evaluating the efficacy and safety of a range of doses and dose escalation schemes of once-per-week eloralintide versus placebo in adults with obesity or overweight and had at least one weight-related comorbidity. Methods: We enrolled 263 participants from 46 research centres in the USA. Individuals aged 18-75 years with a BMI of 30 kg/m 2 or higher, or a BMI of 27 kg/m 2 or higher with at least one weight-related comorbidity and without type 2 diabetes were randomly assigned (2:1:1:1:2:1:2) to receive once-per-week subcutaneous injections of placebo or eloralintide at 1 mg, 3 mg, 6 mg, or 9 mg, or dose escalations of 6-9 mg or 3-9 mg for 48 weeks. The primary endpoint was percent change in bodyweight from baseline after 48 weeks of treatment. Efficacy analyses included all randomly assigned participants, and safety analyses included all participants who were randomly assigned and received at least one dose of study treatment. This study was completed on Aug 14, 2025, and is registered with ClinicalTrials.gov (NCT06230523). Findings: Between Feb 5, 2024, and Aug 14, 2025, 263 participants (mean age 49·0 years [SE 12·6], mean bodyweight 109·1 kg [22·8], BMI 39·1 kg/m 2 [6·8], 204 [78%] female, and 205 [78%] White) were randomly assigned to receive eloralintide (1 mg, n=28; 3 mg, n=24; 6 mg, n=28; 9 mg, n=54; 6-9 mg, n=24; and 3-9 mg, n=52) or placebo (n=53). The efficacy analyses were based on the 263 participants randomly assigned. The mean percent change in bodyweight from baseline after 48 weeks (efficacy estimand) was -9% (1 mg, 95% CI -12·6 to -6·3), -12% (3 mg, -14·9 to -9·8), -18% (6 mg, -20·7 to -14·5), -20% (9 mg, -22·7 to -17·5), -20% (6-9 mg, -22·7 to -17·0), and -16% (3-9 mg, -18·6 to -14·1), compared with -0·4% (-2·2 to 1·4) in the placebo group. The most common adverse events with eloralintide were nausea (1 mg 11%, 3 mg 13%, 6 mg 64%, 9 mg 33%, 6-9 mg 54%, 3-9 mg 25%, and placebo 14%) and fatigue (1 mg 0%, 3 mg 13%, 6 mg 29%, 9 mg 43%, 6-9 mg 46%, 3-9 mg 21%, and placebo 12%). Interpretation: Eloralintide produced clinically meaningful, dose-dependent reductions in bodyweight over 48 weeks and was generally well tolerated, supporting eloralintide's potential use for obesity treatment. Funding: Eli Lilly. (Copyright © 2025 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.) |
| Molecular Sequence: | ClinicalTrials.gov NCT06230523 |
| Substance Nomenclature: | 0 (Anti-Obesity Agents) 0 (Amylin Receptor Agonists) |
| Entry Date(s): | Date Created: 20251109 Date Completed: 20251206 Latest Revision: 20251206 |
| Update Code: | 20251207 |
| DOI: | 10.1016/S0140-6736(25)02155-5 |
| PMID: | 41207310 |
| Databáze: | MEDLINE |
Nájsť tento článok vo Web of Science | Abstrakt: | Background: Amylin-based therapies are emerging as promising obesity medications. Eloralintide is a novel, selective amylin receptor agonist in development for weight management. We performed a phase 2, double blind, randomised, placebo-controlled trial with the aim of evaluating the efficacy and safety of a range of doses and dose escalation schemes of once-per-week eloralintide versus placebo in adults with obesity or overweight and had at least one weight-related comorbidity.<br />Methods: We enrolled 263 participants from 46 research centres in the USA. Individuals aged 18-75 years with a BMI of 30 kg/m <sup>2</sup> or higher, or a BMI of 27 kg/m <sup>2</sup> or higher with at least one weight-related comorbidity and without type 2 diabetes were randomly assigned (2:1:1:1:2:1:2) to receive once-per-week subcutaneous injections of placebo or eloralintide at 1 mg, 3 mg, 6 mg, or 9 mg, or dose escalations of 6-9 mg or 3-9 mg for 48 weeks. The primary endpoint was percent change in bodyweight from baseline after 48 weeks of treatment. Efficacy analyses included all randomly assigned participants, and safety analyses included all participants who were randomly assigned and received at least one dose of study treatment. This study was completed on Aug 14, 2025, and is registered with ClinicalTrials.gov (NCT06230523).<br />Findings: Between Feb 5, 2024, and Aug 14, 2025, 263 participants (mean age 49·0 years [SE 12·6], mean bodyweight 109·1 kg [22·8], BMI 39·1 kg/m <sup>2</sup> [6·8], 204 [78%] female, and 205 [78%] White) were randomly assigned to receive eloralintide (1 mg, n=28; 3 mg, n=24; 6 mg, n=28; 9 mg, n=54; 6-9 mg, n=24; and 3-9 mg, n=52) or placebo (n=53). The efficacy analyses were based on the 263 participants randomly assigned. The mean percent change in bodyweight from baseline after 48 weeks (efficacy estimand) was -9% (1 mg, 95% CI -12·6 to -6·3), -12% (3 mg, -14·9 to -9·8), -18% (6 mg, -20·7 to -14·5), -20% (9 mg, -22·7 to -17·5), -20% (6-9 mg, -22·7 to -17·0), and -16% (3-9 mg, -18·6 to -14·1), compared with -0·4% (-2·2 to 1·4) in the placebo group. The most common adverse events with eloralintide were nausea (1 mg 11%, 3 mg 13%, 6 mg 64%, 9 mg 33%, 6-9 mg 54%, 3-9 mg 25%, and placebo 14%) and fatigue (1 mg 0%, 3 mg 13%, 6 mg 29%, 9 mg 43%, 6-9 mg 46%, 3-9 mg 21%, and placebo 12%).<br />Interpretation: Eloralintide produced clinically meaningful, dose-dependent reductions in bodyweight over 48 weeks and was generally well tolerated, supporting eloralintide's potential use for obesity treatment.<br />Funding: Eli Lilly.<br /> (Copyright © 2025 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.) |
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| ISSN: | 1474-547X |
| DOI: | 10.1016/S0140-6736(25)02155-5 |