SLGT2-Inhibitors Decrease Risk for MACEs in Patients With Type 2 Diabetes

Sodium-glucose cotransporter 2- (SGLT2-) inhibitor therapy reduces atherosclerotic plaque progression, leading to favorable cardiovascular outcomes, according to research published in Cardiovascular Diabetology.

Researchers aimed to evaluate the effect SGLT2-inhibitors have on multivessel nonobstructive coronary artery lesions in terms of plaque morphology, inflammatory burden, and major adverse cardiovascular events (MACEs).

An international, multicenter observational study was conducted by researchers at the Department of Cardiology of the Cardarelli Hospital in Naples, Italy. Patients were screened from 2013 to 2021 for evidence of stable ischemic heart disease and multivessel nonobstructive coronary artery lesions with normal fractional flow reserve (FFR >.80), as well as a confirmed diagnosis of type 2 diabetes. Those with a history of previous myocardial infarction, percutaneous intervention and/or coronary bypass grafting were excluded from the study.

The primary endpoint was fibrous cap thickness, evaluated at baseline and at 1-year follow-up using optical coherence tomography (OCT). Secondary endpoints included serum inflammatory status (measured by circulation molecular and cellular pathways) and end rate of MACEs, defined by cardiovascular disease events, hospital admissions for heart failure and ischemic cardiovascular events. 

Cohorts were initially evaluated using physical examinations, history of MACEs as well as hospital visits and discharge schedules. Noninvasive stress test were performed to categorize patients as positive or negative , the former defined as moderate to severe reversible defect on nuclear perfusion imaging (≥10% ischemic myocardium).

Patients were followed up using serum analysis for biochemical and inflammatory markers. Coronary angiography as well as OCT was done for fibrous cap thickness. Fibrous cap thickness was graded using a macrophage grading system.

In total, 111 study patients were receiving SGLT2-inhibitor therapy and 258 study patients were receiving non-SGLT2-inhibitor therapy. Patients taking SGLT2-inhibitors received either daily 10-mg or 25-mg empagliflozin, 100-mg canagliflozin, and/or 10-mg dapagliflozin. Non-SGLT2-inhibitor patients were treated with other classes of hypoglycemic drugs.

At 6- and 12-month follow-up, patients on SGLT2-inhibitor therapy had lower body mass index, hemoglobin A_1c, inflammatory cells (white blood cells, granulocytes, monocytes), and inflammation-related molecules (C-reactive protein, IL-6, tumor necrosis factor alpha; P <.05)

Patients receiving SGLT2-inhibitor therapy at 12 months follow-up had the highest values of minimal fibrous cap thickness, evidenced by OCT. Additionally, the SGLT2-inhibitor group had a lower rate of MACEs compared with the non-SGLT2-inhibitor group (10.8% vs 22.1%; P <.05).

Cox regression models showed that hemoglobin A_1c values (1.930; 95% CI, 1.149-2.176), SGLT2-inhibitor therapy (0.342; 95% CI, 0.180–0.651), and macrophage grade (1.188; 95% CI, 1.073–1.315) were independent predictors of MACEs at 12-month follow-up.

Limitations of the study include lack of randomization. Additionally, limiting follow-up to 1 year could restrict the generalizability of the study results.

“In our study, SGLT2-I [inhibitor] reduced by half the MACEs in the Mv-NOCS [multivessel nonobstructive coronary artery lesions] diabetic patients (best clinical outcomes),” the study authors wrote. “The introduction of SGLT2-I therapy post coronary angiography and OCT may be predictive of the 65% of risk reduction of MACEs at 1 year of follow-up.”