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KMID : 1200020220460060843
Diabetes & Metabolism Journal
2022 Volume.46 No. 6 p.843 ~ p.854
Comparison of Serum Ketone Levels and Cardiometabolic Efficacy of Dapagliflozin versus Sitagliptin among Insulin-Treated Chinese Patients with Type 2 Diabetes Mellitus
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
Abstract
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.
KEYWORD
Dapagliflozin, Diabetes mellitus, type 2, Heart disease risk factors, Ketones, Sitagliptin phosphate
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