Diabetes Mellitus, Stroke
Conditions
Keywords
stroke, diabetes mellitus, sodium-glucose transport protein 2 inhibitor, pioglitazone
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.
Interventions
DRUGMetformin plus Pioglitazone plus an SGLT2 inhibitor
Patients assigned to active group will stop their prior oral antidiabetic drugs and receive combination of metformin, pioglitazone, and an SGLT2 inhibitor (empagliflozin or dapagliflozin or canagliflozin) and dose will be adjusted by their physicians.
Sponsors
National Taiwan University Hospital
Chiayi Christian Hospital
Tainan Sin-lau Hospital
Chang Gung Memorial Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to 99 Years
Healthy volunteers
No
Inclusion criteria
1. Ischemic stroke within 3 months of randomization 2. Type 2 diabetes mellitus and Hba1C \> 7.0% and under metformin therapy currently or previously 3. Estimated glomerular filtration rate (eGFR) ≥ 45 mL/min/1.73 m2 4. Age ≥ 20 y at study entry 5. Ability and willingness to provide informed consent
Exclusion criteria
1. History of congestive heart failure (NYHA class 1-4) 2. History of bladder cancer 3. History of repeated (\> 2 episodes) urinary tract infection or genital tract infection 4. Irreversible medical conditions with predicted survival \< 1 years 5. Current use of an insulin 6. Current use of a glucagon-like peptide-1 receptor agonist 7. Current use of pioglitazone or an SGLT-2 inhibitor
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| HbA1C | 6 months from baseline in active vs control arms | blood test to evaluate glycemic control |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| UACR | 6 months from randomization in active vs control arms | to evaluate microalbuminuria |
| hs-CRP | 6 months from randomization | to evaluate hs-CRP in active vs control arms |
| NT-proBNP | 6 months from randomization | to evaluate NT-proBNP in active vs control arms |
| insulin resistance | 6 months from randomization | Insulin resistance will be evaluated by Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) |
Countries
Taiwan
Contacts
Primary ContactMeng Lee, MD
Outcome results
None listed