KMID : 1200020220460060843
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Diabetes & Metabolism Journal 2022 Volume.46 No. 6 p.843 ~ p.854
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Comparison of Serum Ketone Levels and Cardiometabolic Efficacy of Dapagliflozin versus Sitagliptin among Insulin-Treated Chinese Patients with Type 2 Diabetes Mellitus
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Lee Chi-Ho
Wu Mei Zhen Lui David Tak Wai Chan Darren Shing Hei Fong Carol Ho Yi Shiu Sammy Wing Ming Wong Ying Lee Alan Chun Hong Lam Joanne King Yan Woo Yu-Cho Lam Karen Siu Ling Yiu Kelvin Kai Hang Tan Kathryn Choon Beng
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Abstract
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Background : Insulin-treated patients with long duration of type 2 diabetes mellitus (T2DM) are at increased risk of ketoacidosis related to sodium-glucose co-transporter 2 inhibitor (SGLT2i). The extent of circulating ketone elevation in these patients remains unknown. We conducted this study to compare the serum ketone response between dapagliflozin, an SGLT2i, and sitagliptin, a dipeptidyl peptidase-4 inhibitor, among insulin-treated T2DM patients.
Methods : This was a randomized, open-label, active comparator-controlled study involving 60 insulin-treated T2DM patients. Participants were randomized 1:1 for 24-week of dapagliflozin 10 mg daily or sitagliptin 100 mg daily. Serum ¥â-hydroxybutyrate (BHB) levels were measured at baseline, 12 and 24 weeks after intervention. Comprehensive cardiometabolic assessments were performed with measurements of high-density lipoprotein cholesterol (HDL-C) cholesterol efflux capacity (CEC), vibration-controlled transient elastography and echocardiography.
Results : Among these 60 insulin-treated participants (mean age 58.8 years, diabetes duration 18.2 years, glycosylated hemoglobin 8.87%), as compared with sitagliptin, serum BHB levels increased significantly after 24 weeks of dapagliflozin (P=0.045), with a median of 27% increase from baseline. Change in serum BHB levels correlated significantly with change in free fatty acid levels. Despite similar glucose lowering, dapagliflozin led to significant improvements in body weight (P=0.006), waist circumference (P=0.028), HDL-C (P=0.041), CEC (P=0.045), controlled attenuation parameter (P=0.007), and liver stiffness (P=0.022). Average E/e¡¯, an echocardiographic index of left ventricular diastolic dysfunction, was also significantly lower at 24 weeks in participants treated with dapagliflozin (P=0.037).
Conclusion : Among insulin-treated T2DM patients with long diabetes duration, compared to sitagliptin, dapagliflozin modestly increased ketone levels and was associated with cardiometabolic benefits.
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KEYWORD
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Dapagliflozin, Diabetes mellitus, type 2, Heart disease risk factors, Ketones, Sitagliptin phosphate
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