Worldwide inertia to the use of cardiorenal protective glucose-lowering drugs (SGLT2i and GLP-1 RA) in high-risk patients with type 2 diabetes

Abstract

The disclosure of proven cardiorenal benefits with certain antidiabetic agents was supposed to herald a new era in the management of type 2 diabetes (T2D), especially for the many patients with T2D who are at high risk for cardiovascular and renal events. However, as the evidence in favour of various sodium–glucose transporter-2 inhibitor (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1 RA) accumulates, prescriptions of these agents continue to stagnate, even among eligible, at-risk patients. By contrast, dipeptidyl peptidase-4 inhibitors (DPP-4i) DPP-4i remain more widely used than SGLT2i and GLP-1 RA in these patients, despite a similar cost to SGLT2i and a large body of evidence showing no clear benefit on cardiorenal outcomes. We are a group of diabetologists united by a shared concern that clinical inertia is preventing these patients from receiving life-saving treatments, as well as placing them at greater risk of hospitalisation for heart failure and progression of renal disease. We propose a manifesto for change, in order to increase uptake of SGLT2i and GLP-1 RA in appropriate patients as a matter of urgency, especially those who could be readily switched from an agent without proven cardiorenal benefit. Central to our manifesto is a shift from linear treatment algorithms based on HbA1c target setting to parallel, independent considerations of atherosclerotic cardiovascular disease, heart failure and renal risks, in accordance with newly updated guidelines. Finally, we call upon all colleagues to play their part in implementing our manifesto at a local level, ensuring that patients do not pay a heavy price for continued clinical inertia in T2D.

Sodium–glucose transporter-2 inhibitors for prevention and treatment of cardiorenal complications of type 2 diabetes

“…embracing the five components of SGLT-2i (empagliflozin, canagliflozin, dapagliflozin, ertugliflozin and sotagliflozin), as emerged by outcome trials. It is sad to acknowledge that, despite the continuing accumulation of data regarding the benefits of SGLT-2i which are incorporated in newly updated guidelines, many eligible patients with T2D are still not receiving these agents, depriving them of protection against the progression of avoidable cardiorenal complications [77].…”

Can glucose-lowering drugs affect the prognosis of COVID-19 in patients with type 2 diabetes?

“…On the basis of evidence from smaller studies, Lim and colleagues 8 recommended that DPP-4 inhibitors be used across a broad spectrum of COVID-19 severity, but that SGLT2 inhibitors should only be used with caution, and metformin should be stopped in severe cases. Because positive results with respect to all-cause mortality have previously been reported for metformin and SGLT2 inhibitors, 9 withdrawal or non-use of these drugs could have a negative effect on the prognosis of patients with type 2 diabetes and COVID-19. Given the large cohort in Khunti and colleagues' study 4 and the absence of evidence for risk with these drugs, recommendations on the use of glucose-lowering drugs by people with type 2 diabetes during the COVID-19 pandemic might now become more liberal, allowing use of all glucose-lowering drugs in stable situations.…”

Transposition of cardiovascular outcome trial effects to the real-world population of patients with type 2 diabetes

“…To the best of our knowledge, there is no prior attempt to transpose effects of diabetes medications observed in CVOTs to a real-world population, with quantitative estimates. Thus, our new findings can help reducing inertia in the use of GLM for which solid cardiorenal protective data exist [ 35 ].…”