OBJECTIVE This analysis of 3,375 adults with overweight/obesity across the Semaglutide Treatment Effect in People with obesity (STEP) 1, 3, and 4 trials evaluated whether more participants with prediabetes had normoglycemia after 68 weeks’ treatment with once-weekly semaglutide 2.4 mg plus lifestyle intervention versus placebo and assessed changes in glucose metabolism in participants with prediabetes. RESEARCH DESIGN AND METHODS STEP 1, 3, and 4 were phase 3, 68-week, randomized, placebo-controlled, multinational trials; STEP 4 had a 20-week semaglutide run-in and 48-week randomized period. Analyses included changes (week 0–68; before the washout period) in glycemic status (prespecified: STEP 1 and 3; post hoc: STEP 4), and in HbA1c, fasting plasma glucose (FPG), and HOMA insulin resistance (HOMA-IR) among participants with prediabetes (post hoc). RESULTS Significantly more participants with baseline (week 0) prediabetes (n = 1,536) had normoglycemia at week 68 with semaglutide versus placebo (STEP 1, 84.1% vs. 47.8%; STEP 3, 89.5% vs. 55.0%; STEP 4, 89.8% vs. 70.4%; all P < 0.0001). Fewer participants with baseline normoglycemia had prediabetes at week 68 with semaglutide versus placebo (STEP 1, 2.9% vs. 10.9%; STEP 3, 3.2% vs. 5.8%; STEP 4, 1.1% vs. 5.0%). Semaglutide resulted in greater improvements in HbA1c, FPG, and HOMA-IR than placebo among participants with baseline prediabetes (all P < 0.01). CONCLUSIONS STEP 1, 3, and 4 collectively provide a robust assessment of the effects of semaglutide on glucose metabolism and prediabetes in a large cohort of adults with overweight/obesity while on treatment. Among participants with baseline prediabetes, 68 weeks’ treatment with semaglutide versus placebo led to significant improvements in glucose metabolism and a higher likelihood of normoglycemia.

中文翻译：

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在 STEP 计划中患有前驱糖尿病的参与者中，每周一次皮下注射 Semaglutide 2.4 mg 会改变葡萄糖代谢和血糖状态

目的 对 3,375 名超重/肥胖成人进行的 Semaglutide 对肥胖患者的治疗效果 (STEP) 1、3 和 4 项试验的分析评估了在每周一次 2.4 mg 的 semaglutide 治疗 68 周后是否有更多的糖尿病前期参与者血糖正常。生活方式干预与安慰剂比较，并评估了糖尿病前期参与者的葡萄糖代谢变化。研究设计和方法 步骤 1、3 和 4 是 3 期、68 周、随机、安慰剂对照的多国试验；STEP 4 有 20 周的 semaglutide 磨合期和 48 周的随机期。分析包括血糖状态（预设：第 1 步和第 3 步；事后：第 4 步）和 HbA1c、空腹血糖 (FPG) 和 HOMA 胰岛素抵抗 (HOMA- IR）在糖尿病前期（事后）的参与者中。结果 与安慰剂相比，基线（第 0 周）前驱糖尿病患者（n = 1,536）在第 68 周时血糖正常（第 1 步，84.1% 对 47.8%；第 3 步，89.5% 对 55.0%；第 4 步，89.8 % 对 70.4%；所有 P < 0.0001)。与安慰剂相比，基线血糖正常的参与者在第 68 周发生糖尿病前期的人数较少（第 1 步，2.9% 对 10.9%；第 3 步，3.2% 对 5.8%；第 4 步，1.1% 对 5.0%）。在基线糖尿病前期的参与者中，与安慰剂相比，索马鲁肽在 HbA1c、FPG 和 HOMA-IR 方面的改善更大（所有 P < 0.01）。结论 步骤 1、3 和 4 共同提供了对 semaglutide 对接受治疗期间超重/肥胖的大量成年人的葡萄糖代谢和前驱糖尿病的影响的有力评估。在基线糖尿病前期的参与者中，