The current role of SGLT2 inhibitors in type 2 diabetes and beyond: a narrative review

ABSTRACT

Introduction

Sodium-glucose cotransporter 2 inhibitors (SGLT2is, gliflozins), the most recent oral antihyperglycaemic agents, provide a cardiorenal protection, an effect independent of their glucose-lowering potency.

Areas covered

The antihyperglycaemic potency of SGLT2is was compared with that of dipeptidyl peptidase-4 inhibitors and glucagon-like peptide-1 receptor agonists, especially when added to metformin monotherapy. Main results of cardiovascular/renal outcome trials with SGLT2is were summarized in different populations: patients with type 2 diabetes mellitus (T2DM) with or without established cardiovascular disease, patients (with or without T2DM) with heart failure (with reduced or preserved left ventricular ejection fraction) and in patients (with or without T2DM) with chronic kidney disease (CKD, including stage 4). Original papers and meta-analyses of these different trials have consistently reported a reduction in hospitalization for heart failure (alone or combined with cardiovascular mortality) and a reduced progression of CKD, with an overall good safety profile.

Expert opinion

Global use of SGLT2is has increased over time but remains suboptimal despite clinically relevant cardiovascular and renal protection, particularly in patients most likely to benefit. SGLT2is has proven both positive benefit–risk balance and cost-effectiveness in at risk patients. New prospects are expected in other complications, i.e. metabolic-associated fatty liver disease and neurodegenerative disorders.

KEYWORDS:

• Cardiovascular disease
• cardiovascular mortality
• chronic kidney disease
• gliflozin
• guidelines
• heart failure
• SGLT2 inhibitor

Article highlights

• Glucose-lowering agents like SGLT2is offer a cardiorenal protection independently of glucose control

• SGLT2is reduce the risk of hospitalization for heart failure (alone or combined with cardiovascular mortality) in different at-risk populations

• SGLT2i efficacy is now proven in patients with all-type heart failure (with reduced or preserved ejection fraction)

• The renal protection was confirmed in all subgroups of estimated glomerular filtration rate, yet the relative effect was more marked in patients with higher baseline levels.

• These remarkable results with an acceptable safety profile and a cost–benefit ratio gave a prominent role of SGLT2is in international guidelines among patients with (and without) diabetes.

Declaration of interest

AJ Scheen has received lecturer/scientific advisor/clinical investigator fees from AstraZeneca, Boehringer Ingelheim, Eli Lilly, GlaxoSmithKline, Janssen, Merck Sharp & Dohme, NovoNordisk and Sanofi. He worked as a clinical investigator in TECOS, LEADER, HARMONY OUTCOME, PIONEER 6, EMPA-REG OUTCOME, CANVAS-R and DECLARE-TIMI 58 cardiovascular outcome trials.

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.