SGLT-2 inhibitors and metformin CV outcomes in type 2 diabetes are broadly similar but SGLT-2 inhibitors slightly reduce heart failure mortality, according to a study from Harvard University
SGLT-2 inhibitors and metformin when started in patients with type 2 diabetes lead to a similar level of cardiovascular outcomes such as myocardial infarction, stroke and death although use of SGLT-2 inhibitors gives rise to a slightly lower risk of both hospitalisation for heart failure and subsequent mortality. This was the conclusion of a cohort study by a team from Harvard University, Boston, USA.
Sodium-glucose cotransporter-2 inhibitors such as empagliflozin, while primarily indicated for the management of type 2 diabetes, have also been shown to reduce cardiovascular events when added to standard care. In addition, 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. Therefore although SGLT-2 inhibitors and metformin are treatments for patients with type 2 diabetes, both have additional cardiovascular benefits. Moreover, the combination of SGLT-2 inhibitors and metformin as a first-line treatment for patients with type 2 diabetes has been suggested as a cost-effective strategy for the management of both type2 diabetes and cardiovascular disease. Nevertheless, there is uncertainty over 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 examined the level of cardiovascular outcomes in patients started on either an SGLT-2 inhibitors or metformin as mono-therapy based on information held within two large commercial health insurance databases. The researchers focused on adults (> 18 years of age) with a diagnosis of type 2 diabetes and new prescription for SGLT-2 inhibitors or metformin. Individuals were then followed-up until the occurrence of a study outcome, death or discontinuation of treatment. The two primary outcomes of interest were 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 8613 first-time SGLT-2 patients were matched to 17,226 metformin users, with a mean age of 60 years (approximately 51% male). Individuals prescribed SGLT-2 inhibitors 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-2 inhibitor use was associated with a lower risk of HHF (HR = 0.80, 95% CI 0.66 – 0.97). When each of the outcomes in the two composite endpoints 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-2 inhibitors or metformin was associated with a similar risk of adverse cardiovascular outcomes, although SGLT-2 inhibitor use was linked to a lower risk of hospitalisation and mortality due to heart failure. However, the authors 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