BACKGROUND Few prospective studies have compared the cardiovascular benefits of sodium-glucose cotransporter-2 (SGLT2) inhibitors and dipeptidyl peptidase 4 (DPP-4) inhibitors. We aimed to clarify the efficacy of dapagliflozin versus sitagliptin for modulating cardiometabolic risk factors including high glycated hemoglobin (HbA1c) levels, hypoglycemia, and body weight. METHODS This prospective, randomized, open-label, blinded-endpoint, parallel-group trial enrolled 340 Japanese patients with early-stage type 2 diabetes receiving metformin alone or no glucose-lowering agents, who were randomized to receive dapagliflozin or sitagliptin for 24 weeks. The primary endpoint was the proportion of patients who achieved the composite endpoint of HbA1c level maintenance < 7.0% (53 mmol/mol), avoidance of hypoglycemia (maintenance of sensor glucose ≥ 3.0 mmol/L or ≥ 54 mg/dL), and ≥ 3.0% body weight loss from baseline. Secondary endpoints included components of the primary endpoint, other metabolic indices, and glucose variability indices measured using flash glucose monitoring. RESULTS Clinical characteristics of patients were age, 58.1 ± 12.2 years; known duration of diabetes, 5.8 ± 6.1 years; body weight, 74.7 ± 14.2 kg; body mass index, 27.9 ± 4.1 kg/m2; and HbA1c level, 7.8 ± 0.8% at baseline. The achievement ratio of primary endpoint was significantly higher in the dapagliflozin group than in the sitagliptin group (24.4% vs. 13.8%, P < 0.05). While the rates of HbA1c level maintenance < 7.0% (53 mmol/mol) and avoidance of hypoglycemia were comparable between the groups (49.4 vs. 50.0% and 88.7 vs. 92.3% for dapagliflozin vs. sitagliptin, respectively), body weight loss of ≥ 3.0% was significantly achieved in the dapagliflozin group (54.4 vs. 19.6%, P < 0.001). Moreover, dapagliflozin was superior to sitagliptin regarding several secondary endpoints that modulate cardiometabolic risk, namely reducing fasting plasma glucose, insulin, uric acid, increasing high-density lipoprotein cholesterol, and suppressing the increase in serum creatinine and the decrease in estimated glomerular filtration rate. On the other hand, sitagliptin was superior to dapagliflozin in suppressing glucose variability. CONCLUSIONS Compared to sitagliptin, dapagliflozin was significantly more effective at improving cardiometabolic risk factors, suggesting that SGLT2 inhibitors might be more suitable than DPP-4 inhibitors for preventing cardiovascular events in patients with early-stage but inadequately controlled type 2 diabetes. Trial registration Trial number, UMIN000028014; registered on June 30, 2017.

中文翻译：

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达格列净与西他列汀对日本2型糖尿病患者心脏代谢危险因素的疗效：一项前瞻性随机研究（DIVERSITY-CVR）。

背景技术很少有前瞻性研究比较过钠葡萄糖共转运蛋白2（SGLT2）抑制剂和二肽基肽酶4（DPP-4）抑制剂在心血管方面的益处。我们旨在阐明达格列净与西他列汀在调节心脏代谢风险因素（包括高糖化血红蛋白（HbA1c）水平，低血糖症和体重）中的功效。方法这项前瞻性，随机，开放标签，无盲点，平行分组的研究纳入了340例日本早期2型糖尿病患者，仅接受二甲双胍或无降糖药，并随机接受达格列净或西他列汀治疗24周。主要终点是达到HbA1c水平维持复合终点<7.0％（53 mmol / mol），避免低血糖（维持传感器葡萄糖≥3）的患者比例。0毫摩尔/升或≥54毫克/分升），且与基线相比体重减轻≥3.0％。次要终点包括主要终点的成分，其他代谢指标和使用快速血糖监测仪测得的葡萄糖变异性指标。结果患者的临床特征为年龄58.1±12.2岁；已知糖尿病持续时间为5.8±6.1年；体重，74.7±14.2公斤; 体重指数，27.9±4.1 kg / m2; 和HbA1c水平，基线时为7.8±0.8％。达格列净组的主要终点达成率显着高于西他列汀组（24.4％vs. 13.8％，P <0.05）。尽管两组之间HbA1c水平维持率<7.0％（53 mmol / mol）和避免低血糖的发生率相当（达格列净与西他列汀分别为49.4比50.0％和88.7比92.3％），但体重减轻≥3。达格列净组显着达到0％（54.4对19.6％，P <0.001）。此外，就调节心脏代谢风险的几个次要终点而言，达格列净优于西格列汀，即降低空腹血浆葡萄糖，胰岛素，尿酸，增加高密度脂蛋白胆固醇，抑制血清肌酐的升高和估计的肾小球滤过率的降低。另一方面，西他列汀在抑制葡萄糖变异性方面优于达格列净。结论与西他列汀相比，达格列净在改善心脏代谢危险因素方面更有效，这表明SGLT2抑制剂可能比DPP-4抑制剂更适合预防早期但未得到充分控制的2型糖尿病患者的心血管事件。试用注册试用号，UMIN000028014；于2017年6月30日注册。