Pioglitazone and SGLT2 Inhibitors vs. DPP4 Inhibitors in Patients With Stroke

Chang Gung Medical Foundation

Status and phase: Enrolling; Phase 2

Conditions: Stroke; Diabetes Mellitus

Treatments: Drug: Metformin plus Pioglitazone plus an SGLT2 inhibitor

Study type: Interventional

Funder types: Other

Identifiers

NCT04419337

MOST 108-2314-B-182-017-

Details and patient eligibility

About

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.

Enrollment: 200 estimated patients

Sex: All

Ages: 20 to 99 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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200 participants in 2 patient groups

Active arm

Experimental group

Description:

metformin+pioglitazone+an SGLT2 inhibitor

Treatment:

Drug: Metformin plus Pioglitazone plus an SGLT2 inhibitor

Control arm

Active Comparator group

Description:

metformin + DPP4 inhibitors

Treatment:

Drug: Metformin plus Pioglitazone plus an SGLT2 inhibitor