Elecoglipron, an oral small molecule GLP-1 receptor agonist in adults with type 2 diabetes (SOLSTICE): a multicentre, phase 2b, randomised, placebo-controlled trial
Abstract
Background: Elecoglipron is an oral, small molecule glucagon-like peptide (GLP)-1 receptor agonist currently in development for the management of type 2 diabetes. Elecoglipron is orally administered once daily with no food or fluid restrictions. SOLSTICE, a phase 2b study, evaluated the efficacy, safety, and tolerability of elecoglipron versus placebo in participants with type 2 diabetes.
Methods: This phase 2b, randomised, double-blind, placebo-controlled trial was conducted in medical research centres and hospitals across nine countries, Canada, Germany, Hungary, Japan, Poland, Slovakia, Spain, the UK, and the USA. Sites were selected based on their capacity to fulfil protocol requirement, including, but not limited to, regulatory and ethics approvals, appropriate infrastructure and personnel, and access to the target patient population. Participants aged 18 years and older with a BMI of 23 kg/m2 or higher and type 2 diabetes (glycated haemoglobin [HbA1c] ≥7·0% to ≤10·5%, ≥6·5% to ≤10·5% in the USA) managed with diet and exercise alone or monotherapy with metformin or an SGLT2 inhibitor were enrolled. Participants were randomly assigned (3:5:3:5:3:3:6:4) via an interactive web response system to elecoglipron as oral once-daily tablets without dose escalation (5, 15, or 25 mg) or three different dose-escalation regimens, to target doses of 50 mg and 75 mg. The daily dose of 50 mg was evaluated using an every 2-week dose-escalation schedule, while 75 mg was assessed with every 2-week or every 4-week dose-escalation schedules. Participants could also be randomly assigned to placebo matched to each of the elecoglipron groups, or open-label oral semaglutide titrated to 14 mg once daily for 26 weeks. Participants, the treating physician, and the sponsor were masked to doses of elecoglipron or matched placebo, while semaglutide was open-label. The primary endpoint was percent change in HbA1c from baseline to 26 weeks. Efficacy, safety, and tolerability were assessed in all participants who received at least one dose of trial treatment. The trial is registered with ClinicalTrials.gov (NCT06579105) and clinicaltrials.eu (2024-512562-34-00) and is completed.
Findings: From Oct 8, 2024, to June 6, 2025, 863 individuals were screened for study inclusion, 457 were excluded as they did not meet the inclusion criteria or met the exclusion criteria, 406 were enrolled and randomly assigned to one of the eight treatment groups, and 404 participants received at least one dose of trial treatment. Among those who received at least one dose of trial treatment, mean (SD) baseline characteristics were: age 58·4 years (10·7); HbA1c of 7·9% (0·9); bodyweight of 99·8 kg (22·1); and BMI of 34·9 kg/m2 (7·5). Of 404 participants, 168 (42%) of participants were female and 236 (58%) were male; 280 (69%) were White. At week 26, the mean change from baseline in HbA1c ranged between -0·91% (95% CI -1·25 to -0·58; 5 mg elecoglipron) and -1·88% (-2·23 to -1·53; 75 mg elecoglipron with every 2-week dose-escalation step) compared with -0·15% (-0·42 to 0·12) with placebo. Adverse events were reported by 63% (24 of 38 in the 5 mg group and 39 of 62 in the 15 mg group) to 87% (33 of 38 in 75 mg every 4-week dose escalation) of participants across elecoglipron doses compared with 63% (45 of 71) in the placebo group. The most common adverse events were gastrointestinal, including nausea, constipation, diarrhoea, and vomiting.
Interpretation: Once-daily oral elecoglipron showed reductions in glycaemia and a safety and tolerability profile consistent with the GLP-1 receptor agonist class at a similar phase of development, supporting continued development with phase 3 trials for people living with type 2 diabetes.
Funding: AstraZeneca.
Authors: Vanita R Aroda, Melanie J Davies, Jill Maaske, Marcus Millegård, Víctor López Juan, Jens Aberle, Andreea Ciudin, Rory J McCrimmon, Olof Eklund, Judy L Shih, Mikaela Sjostrand, Donna Zarzuela, Julio Rosenstock
Journal: Lancet (London, England)