Comparison of the Effects of Dapagliflozin and Gemigliptin on Ketone Metabolism and Cardiac Remodeling in Type 2 Diabetes

Type2 Diabetes Clinical Trial

Official title:

Comparison of the Effects of Dapagliflozin and Gemigliptin on Ketone Metabolism and Cardiac Remodeling in Type 2 Diabetes

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05194592
• Other study ID #: CR121038
• Status: Recruiting
• Phase: Phase 4
• Start date: January 7, 2022
• Est. completion date: June 30, 2025

Study information

• Verified date: July 2023
• Source: Wonju Severance Christian Hospital
• Contact: Dong-Hyuk Cho, MD,PhD
• Phone: 82-33-741-0916
• Email: why012[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Sodium-glucose cotransporter 2 (SGLT2) inhibitors have demonstrated cardiovascular and renal protection in patients with type 2 diabetes (T2D); however, the underlying mechanism remains unclear. We hypothesized that SGLT2 inhibitor will improve the ketone metabolism compared to dipeptidyl Peptidase-4 (DPP4) inhibitor. And we will also evaluate the association between ketone metabolism and cardiac remodeling evaluated by echocardiography. We will randomly assign 122 people with T2DM to receive dapagliflozin 10mg or gemigliptin 50mg. The primary endpoint are changes in acetoacetate, total ketone, beta-hydroxybutyric acid, left ventricular (LV) mass index, and LV global longitudinal strain during 6 months follow-up. This study may provide robust evidence of the thrifty substrate hypothesis for cardiovascular protection of SGLT2 inhibitors.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 122
• Est. completion date: June 30, 2025
• Est. primary completion date: December 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 30 Years to 80 Years

Eligibility

Inclusion Criteria:

• Subjects diagnosed with T2D on stable antidiabetic medication

• No recent use of SGLT2 inhibitor within 3 months

Exclusion Criteria:

• HbA1c > 10%

• Pregnancy or breast feeding

• estimated GFR <45 30 mL/min/1.73?

• insulin user

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Remodeling, Ventricular
• Type2 Diabetes
• Ventricular Remodeling

Intervention

Drug:
• Dapagliflozin
The patients assigned to the Dapagliflozin group will take Farxiga Pill 10mg for 6 months.
• Gemigliptin
The patients assigned to the Gemigliptin group will take Zemiglo Pill 50mg for 6 months.

Locations

Country	Name	City	State
Korea, Republic of	Yonsei University Wonju College of Medicine	Wonju	Gangwondo

Sponsors (1)

Lead Sponsor	Collaborator
Wonju Severance Christian Hospital

Country where clinical trial is conducted

Korea, Republic of, 

References & Publications (6)

Brown AJM, Gandy S, McCrimmon R, Houston JG, Struthers AD, Lang CC. A randomized controlled trial of dapagliflozin on left ventricular hypertrophy in people with type two diabetes: the DAPA-LVH trial. Eur Heart J. 2020 Sep 21;41(36):3421-3432. doi: 10.1093/eurheartj/ehaa419. — View Citation

Correction. J Am Coll Cardiol. 2020 Sep 22;76(12):1505. doi: 10.1016/j.jacc.2020.08.010. No abstract available. — View Citation

Gaborit B, Ancel P, Abdullah AE, Maurice F, Abdesselam I, Calen A, Soghomonian A, Houssays M, Varlet I, Eisinger M, Lasbleiz A, Peiretti F, Bornet CE, Lefur Y, Pini L, Rapacchi S, Bernard M, Resseguier N, Darmon P, Kober F, Dutour A. Effect of empagliflozin on ectopic fat stores and myocardial energetics in type 2 diabetes: the EMPACEF study. Cardiovasc Diabetol. 2021 Mar 1;20(1):57. doi: 10.1186/s12933-021-01237-2. — View Citation

Kim SR, Lee SG, Kim SH, Kim JH, Choi E, Cho W, Rim JH, Hwang I, Lee CJ, Lee M, Oh CM, Jeon JY, Gee HY, Kim JH, Lee BW, Kang ES, Cha BS, Lee MS, Yu JW, Cho JW, Kim JS, Lee YH. SGLT2 inhibition modulates NLRP3 inflammasome activity via ketones and insulin in diabetes with cardiovascular disease. Nat Commun. 2020 May 1;11(1):2127. doi: 10.1038/s41467-020-15983-6. — View Citation

Tikkanen I, Narko K, Zeller C, Green A, Salsali A, Broedl UC, Woerle HJ; EMPA-REG BP Investigators. Empagliflozin reduces blood pressure in patients with type 2 diabetes and hypertension. Diabetes Care. 2015 Mar;38(3):420-8. doi: 10.2337/dc14-1096. Epub 2014 Sep 30. — View Citation

Verma S, McMurray JJV. SGLT2 inhibitors and mechanisms of cardiovascular benefit: a state-of-the-art review. Diabetologia. 2018 Oct;61(10):2108-2117. doi: 10.1007/s00125-018-4670-7. Epub 2018 Aug 22. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change (%) in acetoacetate, total ketone, beta-hydroxybutyric acid	The change of acetoacetate, total ketone, beta-hydroxybutyric acid from baseline to 6 months follow-up	6 months
Primary	Change (%) in LV mass index	The change of LV mass index from baseline to 6 months follow-up	6 months
Secondary	Change (%) in LV ejection global longitudinal strain	The change of LV mass ejection global longitudinal strain from baseline to 6 months follow-up	6 months
Secondary	Change (%) in mean 24hr ambulatory systolic and diastolic blood pressure	The change of mean 24hr ambulatory systolic and diastolic blood pressurefrom baseline to 6 months follow-up	6 months