What is the clinical evidence from this study?

Study design: Cohort. Population: Type 2 Diabetes Mellitus (n=113588). Intervention: Sodium-glucose cotransporter-2 inhibitors (SGLT-2i) vs. Thiazolidinedione (TZD). Primary outcome: Hospitalization with a main diagnosis of stroke (HR 1.054, 95% CI 0.904-1.229, p=0.505).

February 8, 2022Open Access

Comparative Effects of Sodium-Glucose Cotransporter 2 Inhibitor and Thiazolidinedione Treatment on Risk of Stroke among Patients with Type 2 Diabetes Mellitus

Key Result

SGLT-2i treatment was associated with a comparable risk of hospitalization for stroke compared to TZD in patients with type 2 diabetes mellitus (HR 1.054).

Study Design

Type

Cohort (n=113,588)

Structured PICO

Does SGLT-2i reduce hospitalization for stroke in patients with Type 2 Diabetes Mellitus compared to TZD?

Population

113,588 propensity-matched adults aged 18-84 with type 2 diabetes mellitus treated with either SGLT-2i or TZD, followed for a mean of approximately 1.8 years.

Exposure

Sodium-glucose cotransporter-2 inhibitor (SGLT-2i) class (dapagliflozin, empagliflozin, ipragliflozin, or ertugliflozin) prescribed for ≥90 days

Comparator

Thiazolidinedione (TZD) class (pioglitazone or lobeglitazone) prescribed for ≥90 days

Outcome

Hospitalization with a main diagnosis of stroke (ICD-10: I60–I64)hard clinical

In a real-world Korean cohort of patients with type 2 diabetes, SGLT-2i and TZD treatments were associated with a comparable risk of stroke, though SGLT-2i significantly reduced the risk of heart failure hospitalization.

Main Result

Hazard Ratio: 1.054 (95% CI 0.904–1.229)

Absolute Event Rate: 4.22% vs 4.11%

p-value: p=0.505

Limitations

Retrospective and observational nature of the claim database with potential unmeasured confounding factors.
Lack of HbA1c levels and duration of diabetes in the propensity-matching model.
Propensity score matching reduced sample size and might have left imbalances in certain variables.
Inability to categorize ischemic stroke according to its subtypes due to database limitations.
Lack of additional neutral comparators like DPP-4 inhibitors.
Short mean duration of follow-up due to the recent launch of SGLT-2i in Korea.
Results from the Korean population might not be applicable to other populations.

Abstract

BACKGROUND: Although cardiovascular outcome trials using sodium-glucose cotransporter-2 inhibitors (SGLT-2i) showed a reduction in risk of 3-point major adverse cardiovascular events (MACE), they did not demonstrate beneficial effects on stroke risk. Additionally, meta-analysis showed SGLT-2i potentially had an adverse effect on stroke risk. Contrarily, pioglitazone, a type of thiazolidinedione (TZD), has been shown to reduce recurrent stroke risk. Thus, we aimed to compare the effect of SGLT-2i and TZD on the risk of stroke in type 2 diabetes mellitus (T2DM) patients. METHODS: Using the Korean National Health Insurance Service data, we compared a 1:1 propensity score-matched cohort of patients who used SGLT-2i or TZD from January 2014 to December 2018. The primary outcome was stroke. The secondary outcomes were myocardial infarction (MI), cardiovascular death, 3-point MACE, and heart failure (HF). RESULTS: After propensity-matching, each group included 56,794 patients. Baseline characteristics were well balanced. During the follow-up, 862 patients were newly hospitalized for stroke. The incidence rate of stroke was 4.11 and 4.22 per 1,000 person-years for the TZD and SGLT-2i groups respectively. The hazard ratio (HR) of stroke was 1.054 (95% confidence interval CI, 0.904 to 1.229) in the SGLT-2i group compared to the TZD group. There was no difference in the risk of MI, cardiovascular death, 3-point MACE between groups. Hospitalization for HF was significantly decreased in SGLT-2i-treated patients (HR, 0.645; 95% CI, 0.466 to 0.893). Results were consistent regardless of prior cardiovascular disease. CONCLUSION: In this real-world data, the risk of stroke was comparable in T2DM patients treated with SGLT-2i or TZD.

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