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31st May 2022
SGLT-2 inhibitors and metformin when initiated for patients with type 2 diabetes have been shown to have the same cardiovascular outcomes such as myocardial infarction, stroke and death although use of SFLT-2 inhibitors is associated with a slightly lower risk of both hospitalisation and death due to heart failure. These were the key findings from a cohort study analysis by a team based at Harvard University, Boston, USA.
Sodium-glucose cotransporter-2 inhibitors (SGLT-2i) such as empagliflozin, although primarily used in the management of type 2 diabetes, have also been shown to reduce cardiovascular events when added to standard care. In addition, evidence from the UK Prospective Diabetes Study showed that patients assigned to metformin had risk reductions of 32% for any diabetes-related endpoint, 42% for diabetes-related death and 36% for all-cause mortality. Thus, although SGLT-2 inhibitors and metformin are primarily diabetic treatments, it is apparent that both are associated with cardiovascular benefits in diabetic patients. Furthermore, using SGLT-2 inhibitors and metformin as a first-line combination therapy for patients with type 2 diabetes has been suggested as a cost-effective strategy for the management of both type2 diabetes and cardiovascular disease. However, what remains uncertain, is the relative cardiovascular benefits of using either a SGLT-2 inhibitor or metformin as mono-therapy in patients with type 2 diabetes.
In the present study, the US team used information held within two large commercial health insurance databases to compare the incidence of cardiovascular events when either treatment was initiated as mono-therapy. The researchers focused on adults (> 18 years of age) with a diagnosis of type 2 diabetes and those who had new prescription for SGLT-2 inhibitors or metformin. Individuals were followed-up until the occurrence of a study outcome, death or discontinuation of treatment. There were two primary outcomes of interest; a composite of acute myocardial infarction, stroke or all-cause mortality (referred to as ‘mortality’) and a composite of hospitalisation for heart failure or all-cause mortality (HHF). For secondary outcomes, the authors individually assessed the effect of either treatment on different components of the two composites. Individuals were propensity-matched 1:2 (SGLT-2i: metformin).
SGLT-2 inhibitors and metformin
A total of 8,613 first-time SGLT-2i patients were matched to 17,226 metformin users, with a mean age of 60 years (approximately 51% male). Individuals prescribed SGLT-2i were followed for a mean of 10.7 months and metformin users for 12.2 months.
The risk of the composite mortality outcome was not significantly different between the two treatments (hazard ratio, HR = 0.96, 95% CI 0.77 – 1.19). However, SGLT-2i inhibitor use was associated with a lower risk of HHF (HR = 0.80, 95% CI 0.66 – 0.97).
When each of the outcomes were analysed separately, only hospitalisation for heart failure was significantly lower (HR = 0.78, 95% CI 0.62 – 0.97) in those prescribed a SGLT-2i.
Based on these findings, the authors concluded that first-line treatment of type 2 diabetes with SGLT-2i or metformin was associated with a similar risk of adverse cardiovascular outcomes although SGLT-2i use was linked to a lower risk of hospitalisation and mortality due to heart failure. However, the called for a randomised trial to provide more robust evidence to confirm these findings.
Shin JH et al. Cardiovascular Outcomes in Patients Initiating First-Line Treatment of Type 2 Diabetes With Sodium–Glucose Cotransporter-2 Inhibitors Versus Metformin. A Cohort Study Ann Intern Med 2022