Comparison of Combined Pioglitazone and SGLT2 Inhibitors vs. DPP4 Inhibitors in Diabetic Patients With Ischemic Stroke: Rationale and Study Design
Trial Snapshot
- Phase
- Phase 2
- Status
- Recruiting
- Sponsor
- Enrollment
- 200
- Locations
- 1
- Primary Endpoint
- HbA1C
Study Overview
Brief Summary
Introduction: An optimal combination of antidiabetic drugs for diabetic patients with ischemic stroke is not well-established. The objective of this randomized trial is to evaluate whether combination of pioglitazone and a sodium glucose cotransporter 2 (SGLT-2) inhibitor, compared with a dipeptidyl peptidase-4 (DPP-4) inhibitor, reduces recurrent stroke in diabetic patients with recent ischemic stroke.
Methods and analysis: The trial is a randomized, parallel-group study conducted at 7 hospitals in Taiwan. Inclusion criteria are adult patients with a history of ischemic stroke within 3 months, diabetes mellitus with Hba1C > 7%, taking metformin currently or previously, and estimated glomerular filtration rate ≥ 45 mL/min/1.73 m2. Eligible patients who sign the informed consent forms will be randomly assigned in a 1:1 ratio to receive either combination of pioglitazone and an SGLT2 inhibitor (empagliflozin or dapagliflozin or canagliflozin) vs. a DPP4 inhibitor. Primary outcome is change in HbA1C between 6 months and baseline in active vs comparator groups. Additional biomarker outcomes are change in hs-CRP insulin resistance, B type natriuretic peptide, and urine albumin creatinine ratio between 6 months and baseline.
Ethics and dissemination Study protocol was approved by the Institutional Review Board of Chang Gung Memorial Hospital, Chiayi Branch, Taiwan (201702353A3, 201802340A3 and 201902176A3). All participants will be required to sign and date an informed consent form. Study findings will be disseminated via a peer-reviewed journal.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 20 Years to 99 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Ischemic stroke within 3 months of randomization
- •Type 2 diabetes mellitus and Hba1C > 7.0% and under metformin therapy currently or previously
- •Estimated glomerular filtration rate (eGFR) ≥ 45 mL/min/1.73 m2
- •Age ≥ 20 y at study entry
- •Ability and willingness to provide informed consent
Exclusion Criteria
- •History of congestive heart failure (NYHA class 1-4)
- •History of bladder cancer
- •History of repeated (> 2 episodes) urinary tract infection or genital tract infection
- •Irreversible medical conditions with predicted survival < 1 years
- •Current use of an insulin
- •Current use of a glucagon-like peptide-1 receptor agonist
- •Current use of pioglitazone or an SGLT-2 inhibitor
Arms & Interventions
Active arm
metformin+pioglitazone+an SGLT2 inhibitor
Intervention: Metformin plus Pioglitazone plus an SGLT2 inhibitor (Drug)
Control arm
metformin + DPP4 inhibitors
Intervention: Metformin plus Pioglitazone plus an SGLT2 inhibitor (Drug)
Outcomes
Primary Outcomes
HbA1C
Time Frame: 6 months from baseline in active vs control arms
blood test to evaluate glycemic control
Secondary Outcomes
- UACR(6 months from randomization in active vs control arms)
- hs-CRP(6 months from randomization)
- NT-proBNP(6 months from randomization)
- insulin resistance(6 months from randomization)