There are currently limited data regarding the effect of semaglutide 2·4 mg in individuals with obesity and prediabetes in clinical trials. We aimed to assess the efficacy and safety of semaglutide 2·4 mg for weight management and glycaemic control in participants with obesity and prediabetes. STEP 10 was a randomised, double-blind, parallel-group, phase 3 trial done across 30 trial sites in Canada, Denmark, Finland, Spain, and the UK and included participants aged 18 years or older with a BMI of 30 kg/m or higher and prediabetes according to UK National Institute for Health and Care Excellence criteria (defined as having at least one of the following at screening: HbA of 6·0–6·4% [42–47 mmol/mol] or fasting plasma glucose [FPG] of 5·5–6·9 mmol/L). Participants were randomly assigned (2:1) to once-weekly subcutaneous semaglutide 2·4 mg or placebo with diet and physical activity counselling for 52 weeks, followed by a 28-week off-treatment period. Primary endpoints were percentage change in bodyweight and proportion of participants reverting to normoglycaemia (HbA <6·0% [<42 mmol/mol] and FPG <5·5 mmol/L) at week 52 (assessed in all randomly assigned participants by intention to treat). Selective safety data were collected for participants who received at least one dose of study drug. This trial is registered with , , and is complete. Between Sept 16 and Dec 29, 2021, 138 participants were randomly assigned to semaglutide 2·4 mg and 69 to placebo. 147 (71%) were female and 60 (29%) were male; 183 (88%) were White. All randomly assigned participants received at least one dose of study drug. Baseline mean age was 53 years (SD 11), bodyweight 111·6 kg (22·2), BMI 40·1 kg/m (6·9), waist circumference 120·1 cm (14·7), HbA 5·9% (0·3; 41·3 mmol/mol [3·0]), and FPG 5·9 mmol/L (0·6). There was a significantly greater reduction in bodyweight with semaglutide 2·4 mg than with placebo at week 52 (–13·9% [SD 0·7] –2·7% [0·6]; estimated treatment difference –11·2% [95% CI –13·0 to –9·4]; p<0·0001). Greater proportions of participants reverted to normoglycaemia at week 52 with semaglutide 2·4 mg than with placebo (103 [81%] of 127 nine [14%] of 64; odds ratio 19·8 [95% CI 8·7 to 45·2]; p<0·0001). Serious adverse events occurred in 12 (9%) participants receiving semaglutide 2·4 mg versus six (9%) receiving placebo. Adverse events leading to treatment discontinuation occurred in eight (6%) participants in the semaglutide 2·4 mg group versus one (1%) participant in the placebo group. No new safety signals were reported. Semaglutide 2·4 mg provided superior reduction in bodyweight and reversion to normoglycaemia versus placebo in participants with obesity and prediabetes. The safety and tolerability profile was consistent with previous studies and with the GLP-1 receptor agonist class. These findings support the potential use of semaglutide 2·4 mg as a treatment option for individuals with obesity and prediabetes to achieve reversion to normoglycaemia. Novo Nordisk. For the Spanish translation of the abstract see Supplementary Materials section.

中文翻译：

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每周一次的索马鲁肽 2·4 mg 与安慰剂对肥胖和糖尿病前期患者的疗效和安全性（STEP 10）：一项随机、双盲、安慰剂对照、多中心 3 期试验


目前临床试验中关于索马鲁肽 2·4 mg 对肥胖和糖尿病前期个体的影响的数据有限。我们的目的是评估索马鲁肽 2·4 mg 对于肥胖和糖尿病前期参与者进行体重管理和血糖控制的有效性和安全性。 STEP 10 是一项随机、双盲、平行组 3 期试验，在加拿大、丹麦、芬兰、西班牙和英国的 30 个试验地点进行，受试者年龄在 18 岁或以上，BMI 为 30 kg/m2根据英国国家健康与护理卓越研究所的标准，患有或更高的糖尿病前期（定义为筛查时至少满足以下一项条件：HbA 为 6·0–6·4% [42–47 mmol/mol] 或空腹血糖[FPG] 5·5–6·9 mmol/L）。参与者被随机分配 (2:1) 接受每周一次皮下注射 2·4 mg 索马鲁肽或安慰剂，并接受饮食和身体活动咨询，为期 52 周，随后是 28 周的停药期。主要终点是第 52 周时体重变化百分比和恢复正常血糖的参与者比例（HbA <6·0% [<42 mmol/mol] 和 FPG <5·5 mmol/L）（按意向对所有随机分配的参与者进行评估）来治疗）。为接受至少一剂研究药物的参与者收集选择性安全数据。该试用已在 、 、 注册，并已完成。 2021 年 9 月 16 日至 12 月 29 日期间，138 名参与者被随机分配至索马鲁肽 2·4 mg 组，69 名参与者被分配至安慰剂组。 147 名（71%）为女性，60 名（29%）为男性； 183 名（88%）是白人。所有随机分配的参与者均接受至少一剂研究药物。 基线平均年龄为 53 岁 (SD 11)，体重 111·6 kg (22·2)，BMI 40·1 kg/m (6·9)，腰围 120·1 cm (14·7)，HbA 5· 9%（0·3；41·3 mmol/mol [3·0]），FPG 5·9 mmol/L（0·6）。第 52 周时，索马鲁肽 2·4 mg 组的体重下降显着大于安慰剂组 (–13·9% [SD 0·7] –2·7% [0·6]；估计治疗差异 –11·2 % [95% CI –13·0 至 –9·4]；p<0·0001)。与安慰剂组相比，第 52 周时服用索马鲁肽 2·4 mg 的参与者恢复正常血糖的比例更高（127 人中的 103 人 [81%] [64 人中的 9 人 [14%]]；比值比 19·8 [95% CI 8·7 至 45·] 2]；p<0·0001)。接受索马鲁肽 2·4 mg 治疗的参与者有 12 名 (9%) 发生严重不良事件，而接受安慰剂的参与者有 6 名 (9%) 发生严重不良事件。索马鲁肽 2·4 mg 组有 8 名 (6%) 参与者发生了导致治疗中断的不良事件，而安慰剂组中有 1 名 (1%) 参与者发生了不良事件。没有报告新的安全信号。与安慰剂相比，索马鲁肽 2·4 mg 在肥胖和糖尿病前期患者中可显着减轻体重并恢复正常血糖。安全性和耐受性与之前的研究以及 GLP-1 受体激动剂类别一致。这些发现支持索马鲁肽 2·4 mg 作为肥胖和糖尿病前期个体的治疗选择的潜在用途，以实现血糖恢复正常。诺和诺德。有关摘要的西班牙语翻译，请参阅补充材料部分。