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

NCT05194592 | Unknown Phase 4

• 1 other identifier: CR121038
• Study Type: interventional
• Target: 122
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Type2 Diabetes; Remodeling, Ventricular

Outcome Measures

Primary Outcomes (2)

• 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

• Change (%) in LV mass index

  The change of LV mass index from baseline to 6 months follow-up

  6 months

Secondary Outcomes (2)

• Change (%) in LV ejection global longitudinal strain

  6 months

• Change (%) in mean 24hr ambulatory systolic and diastolic blood pressure

  6 months

Study Arms (2)

Dapagliflozin group

ACTIVE COMPARATOR

Dapagliflozin 10mg for 6 months.

Drug: Dapagliflozin

Gemigliptin group

PLACEBO COMPARATOR

Gemigliptin 50mg for 6 months.

Drug: Gemigliptin

Interventions

Dapagliflozin DRUG

The patients assigned to the Dapagliflozin group will take Farxiga Pill 10mg for 6 months.

Dapagliflozin group

Gemigliptin DRUG

The patients assigned to the Gemigliptin group will take Zemiglo Pill 50mg for 6 months.

Gemigliptin group

Eligibility Criteria

• Age: 30 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects diagnosed with T2D on stable antidiabetic medication
• No recent use of SGLT2 inhibitor within 3 months

You may not qualify if:

• HbA1c \> 10%
• Pregnancy or breast feeding
• estimated GFR \<45 30 mL/min/1.73㎡
• insulin user

Sponsors & Collaborators

• Wonju Severance Christian Hospital: lead

Study Sites (1)

Yonsei University Wonju College of Medicine

Wŏnju, Gangwondo, 26426, South Korea

RECRUITING

Related Publications (6)

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

  PMID: 32943171 BACKGROUND

• 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.

  PMID: 25271206 BACKGROUND

• 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.

  PMID: 30132036 BACKGROUND

• 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.

  PMID: 32358544 BACKGROUND

• 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.

  PMID: 33648515 BACKGROUND

• 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.

  PMID: 32578850 BACKGROUND

MeSH Terms

Conditions

Ventricular Remodeling

Interventions

dapagliflozin; LC15-0444

Condition Hierarchy (Ancestors)

Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms

Central Study Contacts

Dong-Hyuk Cho, MD,PhD

CONTACT

82-33-741-0916; why012@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: January 4, 2022
• First Posted: January 18, 2022
• Study Start: January 7, 2022
• Primary Completion: December 31, 2024
• Study Completion: June 30, 2025
• Last Updated: August 1, 2023

Record last verified: 2023-07

Data Sharing

• IPD Sharing: Will not share

Locations

KR (1)