Effects of DPP4 Inhibitor Versus SGLT2 Inhibitor

Phase 4

Completed

• Conditions: Ischemic Heart Disease; Diabetes Mellitus, Type 2
• Interventions: Drug: vildagliptin; Drug: Dapagliflozin

• Registration Number: NCT03178591
• Lead Sponsor: Chiang Mai University

Brief Summary

Type 2 diabetes mellitus (type 2 DM) is an important disease with increasing prevalence worldwide. More than 60% of diabetes patients die of CVD. Diabetes is associated with 2-to 4- fold increase in the risk of coronary artery disease (CAD). Diabetes patients with stable ischemic heart disease may have more prevalent of asymptomatic ischemia or silent ischemia due to autonomic neuropathy. Therefore, detection of total myocardial ischemia including both symptomatic and silent ischemia using ambulatory electrocardiogram monitoring may provide better accuracy in ischemic burden and prognosis in diabetes patients. DDP-4 inhibitors have favorable effects on atherosclerotic risk factors beyond glycemic control. Furthermore, DPP-4 inhibitors may have favorable effects on ischemic preconditioning in patients with CAD. For this study we aim to compare the effects of between vildagliptin and Dapagliflozin on ischemic burden defined by total ischemic time, markers of autonomic function, biomarkers of myocardial injury and biomarkers of inflammation.

Detailed Description

Not available

Study Timeline

• Study Start: 2014-10
• Study First Submitted: 2017-01-09
• Study First Submitted QC: 2017-06-05
• Study First Posted: 2017-06-07
• Status Verified: 2018-07
• Primary Completion: 2018-07
• Study Completion: 2018-07
• Last Update Submitted: 2018-07-17
• Last Update Posted: 2018-07-19

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 43

Inclusion Criteria

1. Adult patients (age > 21), male or non-child bearing potential female

2. Inadequately controlled type 2 diabetes with at least half maximum dose of metformin (HbA1C > 6.5 and < 9.0%)

3. Stable documented CAD defined as the followings:

   1. Stable angina with > 70% stenosis of at least one major epicardial artery from coronary angiogram (CAG) or coronary CTA
   2. Post myocardial infarction (> 30 days)

Exclusion Criteria

1. Significant renal function (eGFR < 30ml/min)
2. Significant hepatic impairment or ALT/AST elevations beyond X2 upper normal limit or known hepatic failure
3. Planned coronary intervention or planed surgical intervention (PCI or CABG)
4. Recent (<30 day) acute coronary syndrome (ACS)
5. Hypersensitivity to either of the study drug components
6. History of lactic acidosis
7. Type 1 diabetes
8. Current HbA1c >9%
9. Current Insulin treatment
10. Active treatment with GLP-1 or other DPP4i medication
11. Inability to comply with study protocol
12. Active malignancy other than basal cell carcinoma
13. Clinically advanced congestive heart failure - NYHA III-IV
14. Severe left ventricular dysfunction (LVEF<25%)
15. Recent heart failure decompensation (<3 months)
16. Chronic inflammation (i.e. inflammatory bowel disease, lupus, inflammatory arthritis, rheumatoid arthritis) or chronic infection (i.e. chronic diabetic foot infection)
17. Pregnancy, lactation or child-bearing potential

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
vildagliptin	vildagliptin	Vildagliptin is a dipeptidyl peptidase-4 inhibitor (DPP-4 inhibitor) Dose of Vildagliptin is 50 mg once or twice daily.
Dapagliflozin	Dapagliflozin	Dapagliflozin is a sodium glucose cotransporter-2 (SGLT-2 inhibitor) Dose of Dapagliflozin is 10 mg once daily.

Primary Outcome Measures

Name	Time	Method
The event of autonomic dysfunction from heart rate variability, heart rate turbulence, QT interval at 6 month between DPP4 inhibitor (vildaglptin) group and SGLT2 inhibitors (Dapagliflozin) group	6 months
The myocardial injury event which verified by hsTnT level at 6 month between DPP4 inhibitor (vildaglptin) group and SGLT2 inhibitors (Dapagliflozin) group	6 months
The ventricular wall stretch event which verified by N-terminal ProBNP level between DPP4 inhibitor (vildaglptin) group and SGLT2 inhibitors (Dapagliflozin) group.	6 months
Number of participants who has ST segment depression in ambulatory ECG monitoring during 24 hours at 6 months between DPP4 inhibitor (vildaglptin) group and SGLT2 inhibitors (Dapagliflozin) group	6 months
Number of myocardial dysfunction which verified by Exercise stress test at 6 month between DPP4 inhibitor (vildaglptin) group and SGLT2 inhibitors (Dapagliflozin) group	6 months
The inflammation event which verified by hsCRP, IL-6 and TNF-alpha level at 6 month between DPP4 inhibitor (vildaglptin) group and SGLT2 inhibitors (Dapagliflozin) group	6 months
The oxidative stress event which verified by MDA and 8-isoprostaglandin F2 alpha level at 6 month between DPP4 inhibitor (vildaglptin) group and SGLT2 inhibitors (Dapagliflozin) group	6 months
The average of systolic blood pressure at 6 month between DPP4 inhibitor (vildaglptin) group and SGLT2 inhibitors (Dapagliflozin) group.	6 months

Trial Locations

Locations (1)

Faculty of Medicine, Chiang Mai University; 🇹🇭 Chiang Mai, Thailand