Efficacy of dapagliflozin versus sitagliptin on cardiometabolic risk factors in Japanese patients with type 2 diabetes: a prospective, randomized study (DIVERSITY-CVR).

Abstract

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.

• Authors: Ayako Fuchigami, Fumika Shigiyama, Toru Kitazawa, Yosuke Okada, Takamasa Ichijo, Mariko Higa, Toru Hiyoshi, Ikuo Inoue, Kaoru Iso, Hidenori Yoshii, Takahisa Hirose, Naoki Kumashiro
• Journal: Cardiovascular diabetology (Cardiovasc Diabetol) Vol. 19 Issue 1 Pg. 1 (01 07 2020) ISSN: 1475-2840 [Electronic] England
• PMID: 31910850 (Publication Type: Comparative Study, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Benzhydryl Compounds
• Biomarkers
• Blood Glucose
• Dipeptidyl-Peptidase IV Inhibitors
• Glucosides
• Glycated Hemoglobin A
• Sodium-Glucose Transporter 2 Inhibitors
• hemoglobin A1c protein, human
• dapagliflozin
• Sitagliptin Phosphate

Topics

• Aged
• Benzhydryl Compounds (adverse effects, therapeutic use)
• Biomarkers (blood)
• Blood Glucose (drug effects, metabolism)
• Cardiovascular Diseases (diagnosis, epidemiology, prevention & control)
• Diabetes Mellitus, Type 2 (diagnosis, drug therapy, epidemiology)
• Dipeptidyl-Peptidase IV Inhibitors (adverse effects, therapeutic use)
• Female
• Glucosides (adverse effects, therapeutic use)
• Glycated Hemoglobin (metabolism)
• Humans
• Japan (epidemiology)
• Male
• Metabolic Syndrome (diagnosis, drug therapy, epidemiology)
• Middle Aged
• Prospective Studies
• Risk Assessment
• Risk Factors
• Sitagliptin Phosphate (adverse effects, therapeutic use)
• Sodium-Glucose Transporter 2 Inhibitors (adverse effects, therapeutic use)
• Time Factors
• Treatment Outcome
• Weight Loss (drug effects)