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

Phase 2

Recruiting

• Conditions: Diabetes Mellitus; Stroke
• Interventions: Drug: Metformin plus Pioglitazone plus an SGLT2 inhibitor

• Registration Number: NCT04419337
• Lead Sponsor: Chang Gung Memorial Hospital

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2019-09-15
• Study First Submitted: 2020-02-26
• Study First Submitted QC: 2020-06-03
• Study First Posted: 2020-06-05
• Status Verified: 2023-03
• Last Update Submitted: 2023-03-28
• Last Update Posted: 2023-03-30
• Primary Completion: 2023-07-31
• Study Completion: 2024-01-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 200

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Control arm	Metformin plus Pioglitazone plus an SGLT2 inhibitor	metformin + DPP4 inhibitors
Active arm	Metformin plus Pioglitazone plus an SGLT2 inhibitor	metformin+pioglitazone+an SGLT2 inhibitor

Primary Outcome Measures

Name	Time	Method
HbA1C	6 months from baseline in active vs control arms	blood test to evaluate glycemic control

Secondary Outcome Measures

Name	Time	Method
UACR	6 months from randomization in active vs control arms	to evaluate microalbuminuria
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)
hs-CRP	6 months from randomization	to evaluate hs-CRP in active vs control arms

Trial Locations

Locations (1)

Chang Gung Memorial Hospital, Chiayi Branch; 🇨🇳 Chiayi City, Taiwan