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/m 2 ; 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.

Sitagliptin significantly improves some lipid parameters while having a comparable effect on blood glucose to nateglinide. A large-scale prospective study of sitagliptin therapy is warranted.

Background: Sodium glucose cotransporter 2 inhibitors (SGLT2i) have attracted attention by the recently reported improved cardiovascular (CV) outcomes in patients with T2DM. In contrast, dipeptidyl peptidase 4 inhibitors (DPP-4i) were reported neutral on CV outcomes. However, there are few prospective studies that have compared the efficacy of SGLT2i and DPP-4i on the prevention of CV disease risks. Therefore, we planned this prospective, randomized, parallel-group trial aimed to compare the therapeutic benefits of dapagliflozin (Dapa) and sitagliptin (Sita) on CV disease risks, with special focus on HbA1c, body weight (BW), and hypoglycemia. Methods: A total of 340 T2DM patients treated with metformin alone or with no glucose-lowering agents (20-80 years of age, HbA1c ≥ 7.1% and &lt; 10.0%) were equally randomized to Dapa 5 mg/day or Sita 50 mg/day add-on group, and treated for 24 weeks. After the 8 weeks, if HbA1c is 7.0% or higher, Dapa and Sita were increased to 10 mg/day and 100 mg/day, respectively. The primary endpoint was the ratio of achieving composite endpoints of the following all 3 items; 1) HbA1c below 7.0%; 2) 3.0% BW loss from baseline; 3) avoidance of hypoglycemia {&lt; 3.0 mmol/L (&lt; 54 mg/dL)}. Hypoglycemia was monitored by flash glucose monitoring system. Results: The achievement ratio of HbA1c below 7.0% was comparable between the groups (49.4 vs. 50.0%, p=1.00, Dapa vs. Sita, respectively). However, 3.0% BW loss was preferably achieved in Dapa group (54.4 vs. 19.6%, p&lt;0.001). There was no significant difference regarding the avoidance of hypoglycemia between the groups (88.7 vs. 92.3%, p=0.27). Thus, the ratio of achieving composite endpoints was superior in Dapa group compared to Sita group (24.4% vs. 13.8%, p&lt;0.05). In summary, Dapa treatment for 24 weeks improved CV risk factors in patients with inadequately controlled T2DM. This study provides the evidence on ideal therapeutic choice for preventing CV events in T2DM. Disclosure A. Fuchigami: None. F. Shigiyama: None. T. Kitazawa: Speaker’s Bureau; Self; AstraZeneca, Daiichi Sankyo Company, Limited, Eli Lilly and Company, Kowa Pharmaceutical Europe Co. Ltd., Kyowa Hakko Kirin Co., Ltd., Mitsubishi Tanabe Pharma Corporation, Novartis Pharmaceuticals Corporation, Novo Nordisk Inc., Ono Pharmaceutical Co., Ltd., Sanofi K.K., Sumitomo Dainippon Pharma Co., Ltd., Takeda Pharmaceutical Company Limited. Y. Okada: None. T. Ichijo: None. M. Higa: None. T. Hiyoshi: Other Relationship; Self; Astellas Pharma Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Daiichi Sankyo Company, Limited, Eli Lilly Japan K.K., Merck Sharp & Dohme Corp., Mitsubishi Tanabe Pharma Corporation, Ono Pharmaceutical Co., Ltd., Sanofi, Sanwa Kagaku Kenkyusho, Taisho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Company Limited. I. Inoue: None. K. Iso: Research Support; Spouse/Partner; AstraZeneca. H. Yoshii: None. T. Hirose: None. N. Kumashiro: Speaker’s Bureau; Self; Novo Nordisk Inc., Sanofi, Takeda Pharmaceutical Company Limited. Funding AstraZeneca K.K.