Sodium-glucose cotransporter 2 inhibitors associated with cardiovascular benefits

26th January 2022

Sodium-glucose cotransporter 2 inhibitors (SGLT2-Is) reduce adverse cardiovascular outcomes according to a meta-analysis of clinical trials

SGLT2-Is can be considered as an effective class of drugs to improve cardiovascular morbidity and mortality. This was the conclusion of a meta-analysis by researchers from the Division of Cardiology, Southern Illinois University School of Medicine, US.

SGLT2-Is were developed and licensed as a class of drugs for the management of type 2 diabetes and one agent in particular, dapagliflozin, has been shown, as an add-on drug to conventional anti-diabetic drugs, to improve glycaemic control. However, with more widespread use of these drugs, it became apparent that there were potential cardioprotective effects, such as a reduction in the worsening of heart failure, irrespective of whether or not the patients were diabetic.

For the present study, the US researchers, set out to establish whether the magnitude of any cardiovascular benefit from SGLT2-Is were generalisable to patients of different ages and ethnicities. They searched for placebo-controlled randomised clinical trials in patients with existing atherosclerotic cardiovascular disease (ASCVD) or the presence of risk factors for ASCVD such as diabetes or heart failure.

They set the primary outcome as cardiovascular death or hospitalisation for heart failure (HHF) and major cardiovascular events (MACE), HHF, cardiovascular death, acute myocardial infarction and all-cause mortality as secondary outcomes. They included gender, age (< 65 or > 65) and ethnicity as subgroups for separate analyses.

Findings

A total of 10 trials including 71,553 patients were analysed with 39,053 who received SGLT2-Is.

The primary outcome of cardiovascular death or HHF was reported in all trials and there were 6921 incidents, 8.1% occurring in those given SGLT2-Is and 11.6% in the placebo group. The use of SGLT2-Is was calculated to be associated with 33% reduced risk of the primary outcome (odds ratio, OR = 0.67, 95% CI 0.55 – 0.80, p < 0.01).

There was also a reduced risk of MACE in those taking SGLT2-Is (OR = 0.90, 95% CI 0.81 – 0.99, p = 0.03). However, there was no difference in the rate of acute myocardial infarction in those taking SGLT2-Is compared to placebo (OR = 0.95, 95% CI 0.87 – 1.03). Moreover, subgroup analysis favoured the use of SGLT2-Is in all groups compared and all-cause mortality was also lower in those taking SGLT2-Is (OR = 0.87, 95% CI 0.80 – 0.96, p = 0.04).

The authors concluded that the ‘cardiovascular outcomes of SGLT2-I therapy can be compared across all trials, and it demonstrates remarkable consistency of class benefit, despite the variations in populations enrolled.’

Citation

Bhattarai M et al. Association of Sodium-Glucose Cotransporter 2 Inhibitors With Cardiovascular Outcomes in Patients With Type 2 Diabetes and Other Risk Factors for Cardiovascular Disease: A Meta-analysis. JAMA 2022