Saxagliptin and Cardiac Structure and Function

• Status: Completed
• Trial end date: 2018-08-01
• Target enrollment: 0
• Participant gender: All

Summary

Diabetes is associated with a substantially increased risk of heart failure, which is associated with substantial morbidity and mortality. Despite the development of new therapeutic strategies to improve glycemic control, recent clinical data from the saxagliptin assessment of vascular outcomes recorded in patients with diabetes mellitus-thrombolysis in myocardial infarction (SAVOR-TIMI) 53 study observed an unexpected finding of an excess of adjudicated heart failure hospitalizations. This excess occurred in the setting of pre-existing heart failure (HF) hospitalization and in those with elevated biomarkers for heart failure such as N terminal pro Brain type natriuretic peptide (NT-pro BNP). A wealth of preclinical data did not suggest a mechanistic basis for an excess of heart failure events, however these preclinical studies primarily focused upon prevention based strategies as opposed to regression studies once established heart failure was present. This proposal seeks to understand if and how dipeptidyl peptidase-4 inhibitors (DPP4i,specifically saxagliptin) may influence the development of heart failure, by evaluating changes in cardiac structure and function using cardiac magnetic resonance imaging (MRI).

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: St. Michael's Hospital, Toronto; Unity Health Toronto
• Treatments: Saxagliptin

Criteria

Inclusion Criteria:

1. Adult (≥18 years old) men or women with type 2 diabetes diagnosed for ≥ 6 months

2. HbA1c 7.5 - 9.5%

3. Receiving background therapy with metformin (additional anti-hyperglycemic agents are permitted)

4. Clinical decision to initiate saxagliptin to improve glycemic control, as per treating physician

Exclusion Criteria:

1. GLP-1 receptor agonist or DPP4 inhibitor treatment within the past 6 months, or known intolerance

2. eGFR <30

3. Baseline LVEF <40%

4. NYHA Class III-IV or recent hospitalization for decompensated HF (<3 months)

5. Unstable coronary syndromes or recent revascularization within the past 3 months, or planned revascularization in the next 6 months

6. Significant (moderate or severe, or symptomatic) valvular disease

7. Pregnancy/childbearing potential

8. Routine contraindications to CMR Subjects who drop out from the study will have a repeat CMR examination as soon as possible after drug discontinuation.