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Chi-Ho Lee 1 Article
Drug/Regimen
Comparison of Serum Ketone Levels and Cardiometabolic Efficacy of Dapagliflozin versus Sitagliptin among Insulin-Treated Chinese Patients with Type 2 Diabetes Mellitus
Chi-Ho Lee, Mei-Zhen Wu, David Tak-Wai Lui, Darren Shing-Hei Chan, Carol Ho-Yi Fong, Sammy Wing-Ming Shiu, Ying Wong, Alan Chun-Hong Lee, Joanne King-Yan Lam, Yu-Cho Woo, Karen Siu-Ling Lam, Kelvin Kai-Hang Yiu, Kathryn Choon-Beng Tan
Diabetes Metab J. 2022;46(6):843-854.   Published online April 28, 2022
DOI: https://doi.org/10.4093/dmj.2021.0319
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  • 4 Web of Science
  • 5 Crossref
AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
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 β-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.

Citations

Citations to this article as recorded by  
  • Serum thrombospondin‐2 level changes with liver stiffness improvement in patients with type 2 diabetes
    Jimmy Ho Cheung Mak, David Tak‐Wai Lui, Carol Ho‐Yi Fong, Chloe Yu‐Yan Cheung, Ying Wong, Alan Chun‐Hong Lee, Ruby Lai‐Chong Hoo, Aimin Xu, Kathryn Choon‐Beng Tan, Karen Siu‐Ling Lam, Chi‐Ho Lee
    Clinical Endocrinology.2024; 100(3): 230.     CrossRef
  • SGLT-2 inhibitors as novel treatments of multiple organ fibrosis
    Junpei Hu, Jianhui Teng, Shan Hui, Lihui Liang
    Heliyon.2024; 10(8): e29486.     CrossRef
  • Effect of sodium-glucose cotransporter protein-2 inhibitors on left ventricular hypertrophy in patients with type 2 diabetes: A systematic review and meta-analysis
    Yao Wang, Yujie Zhong, Zhehao Zhang, Shuhao Yang, Qianying Zhang, Bingyang Chu, Xulin Hu
    Frontiers in Endocrinology.2023;[Epub]     CrossRef
  • Effects of SGLT2 inhibitors on hepatic fibrosis and steatosis: A systematic review and meta-analysis
    Peipei Zhou, Ying Tan, Zhenning Hao, Weilong Xu, Xiqiao Zhou, Jiangyi Yu
    Frontiers in Endocrinology.2023;[Epub]     CrossRef
  • The impact of sodium-glucose Cotransporter-2 inhibitors on lipid profile: A meta-analysis of 28 randomized controlled trials
    Gang Fan, Dian long Guo, Hong Zuo
    European Journal of Pharmacology.2023; 959: 176087.     CrossRef

Diabetes Metab J : Diabetes & Metabolism Journal