Elecoglipron, an oral small molecule GLP-1 receptor agonist in adults with type 2 diabetes (SOLSTICE): a multicentre, phase 2b, randomised, placebo-controlled trial.

Elecoglipron is orally administered once daily with no food or fluid restrictions.

Elecoglipron每天口服一次，无需食物或液体限制。

SOLSTICE, a phase 2b study, evaluated the efficacy, safety, and tolerability of elecoglipron versus placebo in participants with type 2 diabetes.

SOLSTICE是一项2b期研究，评估了在2型糖尿病患者中，elecoglipron与安慰剂相比的有效性、安全性和耐受性。

Methods

This phase 2b, randomised, double-blind, placebo-controlledtrial was conducted in medical research centres and hospitals across nine countries, Canada, Germany, Hungary, Japan, Poland, Slovakia, Spain, the UK, and the USA.

这项2b期、随机、双盲、安慰剂对照试验在九个国家的医疗研究中心和医院进行，这些国家包括加拿大、德国、匈牙利、日本、波兰、斯洛伐克、西班牙、英国和美国。

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.

选择的站点能够满足协议要求，包括但不限于监管和伦理审批、适当的基础设施和人员配备，以及能够接触到目标患者群体。

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.

招募了年龄在18岁及以上的参与者，他们的体质指数（BMI）为23 kg/m2或更高，并且患有2型糖尿病（在美国为糖化血红蛋白[HbA1c]≥7·0%至≤10·5%，在其他国家为≥6·5%至≤10·5%），仅通过饮食和运动管理或使用二甲双胍或SGLT2抑制剂单药治疗。

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.

参与者通过交互式网络响应系统随机分配（3:5:3:5:3:3:6:4），接受口服每日一次的elecoglipron片剂，无需剂量递增（5、15或25毫克），或三种不同的剂量递增方案，以达到50毫克和75毫克的目标剂量。

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.

每日50毫克剂量使用每两周一次的剂量递增方案进行评估，而75毫克则使用每两周或每四周一次的剂量递增方案进行评估。

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.

参与者也可以随机分配到与每个elecoglipron组相匹配的安慰剂，或开放标签的口服semaglutide，剂量调整至每天一次14毫克，持续26周。

Participants, the treating physician, and the sponsor were masked to doses of elecoglipron or matched placebo, while semaglutide was open-label.

参与者、治疗医生和赞助商对elecoglipron或匹配的安慰剂剂量进行了遮蔽，而semaglutide是开放标签的。

The primary endpoint was percent change in HbA1c from baseline to 26 weeks.

主要终点是从基线到26周HbA1c变化的百分比。

Efficacy, safety, and tolerability were assessed in all participants who received at least one dose of trial treatment.

在所有至少接受一次试验治疗的参与者中评估了疗效、安全性和耐受性。

The trial is registered with ClinicalTrials.gov (NCT06579105) and clinicaltrials.eu (2024-512562-34-00) and is completed.

该试验已在ClinicalTrials.gov (NCT06579105)和clinicaltrials.eu (2024-512562-34-00)注册，并已完成。

Results

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.

从2024年10月8日至2025年6月6日，共有863人接受了研究纳入筛查，其中457人因不符合纳入标准或符合排除标准而被排除，406人被纳入研究并随机分配到八个治疗组之一，404名参与者接受了至少一次试验治疗。

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).

在接受至少一次试验治疗的受试者中，基线特征的平均值（标准差）为：年龄58.4岁（10.7）；糖化血红蛋白（HbA1c）为7.9%（0.9）；体重为99.8公斤（22.1）；体质指数（BMI）为34.9公斤/平方米（7.5）。

Of 404 participants, 168 (42%) of participants were female and 236 (58%) were male; 280 (69%) were White.

在404名参与者中，168名（42%）为女性，236名（58%）为男性；280名（69%）为白人。

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.

在第26周时，基线HbA1c的平均变化范围在-0·91%（95%置信区间-1·25至-0·58；5毫克elecoglipron）和-1·88%（-2·23至-1·53；每两周剂量递增75毫克elecoglipron）之间，与安慰剂组的-0·15%（-0·42至0·12）相比。

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.

在elecoglipron剂量组中，63%（5毫克组38人中有24人，15毫克组62人中有39人）至87%（每四周剂量递增75毫克组38人中有33人）的参与者报告了不良事件，与安慰剂组的63%（71人中有45人）相比。

The most common adverse events were gastrointestinal, including nausea, constipation, diarrhoea, and vomiting.

最常见的不良事件是胃肠道相关，包括恶心、便秘、腹泻和呕吐。

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.

每日一次口服的elecoglipron显示出降低血糖的效果，并且其安全性和耐受性与同阶段开发的GLP-1受体激动剂类药物一致，支持为2型糖尿病患者继续进行第三阶段临床试验。

funding

AstraZeneca.

阿斯利康。