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Published in The Lancet Diabetes & Endocrinology, a paper co-authored by seven leading diabetes experts in Europe and the United Sates, including UNC’s John Buse, MD, PhD, warns against medical inertia that prevents physicians from helping patients with type 2 diabetes and cardiorenal disease.

CHAPEL HILL, NC — Large clinical trials involving patients with type 2 diabetes at high cardiovascular risk have led to remarkable advances in our understanding of the effectiveness of two types of diabetes drugs – GLP-1 receptor agonists and SGLT2 inhibitors – to reduce high blood sugar and reduce adverse health events related to the heart and kidney disease. But only a small proportion of patients with diabetes and cardiovascular disease are currently treated with these medications. Moreover, cardiologists very rarely prescribe these potentially life-saving drugs.

A group of seven leading diabetes doctors and cardiologists are trying to change that to help patients live longer, healthier lives. They published a call to action in The Lancet Diabetes & Endocrinology to move the care of these patients forward, based heavily on successful large phase 3 clinical trials for these classes of medications.

In 2019, the American Diabetes Association (ADA), the European Association for the Study of Diabetes (EASD), and European Society of Cardiology (ESC) published updated recommendations for the management of such patients. The recommendations suggest metformin as the first-­line therapy in newly diagnosed type 2 diabetes; however, the ADA–EASD consensus recommends this for all patients with newly diagnosed type 2 diabetes, whereas the ESC guidelines indicate that SGLT2 inhibitors or GLP­1 receptor agonists should be offered first if patients have cardiovascular disease or in patients at high or very high cardiovascular risk. This difference is not profound considering the ADA–EASD consensus report recommends that patients at high risk of heart and/or kidney disease should be treated with SGLT2 inhibitors or GLP­1 receptor agonists, independent of blood sugar levels.

Furthermore, most patients with type 2 diabetes rapidly progress to requiring combination therapy. So, in the context of the ESC treatment approach, the addition of metformin to initial SGLT2 inhibitor or GLP­1 receptor agonist therapy will often be required soon after diagnosis.

Yet, these differing views seem to have caused hesitation in prescribing an SGLT2 inhibitor or GLP1 receptor agonist.

In an article published in The Lancet, leading doctors from Europe and the United States wrote bluntly, “We are concerned that ongoing discussions focusing on the differences between the endocrinologists’ consensus report from the ADA and EASD and cardiologists’ guidelines from the ESC are contributing to clinical inertia, thereby effectively denying evidence-based treatments advocated by both groups to patients with type 2 diabetes and cardiorenal disease,” which is an umbrella term referring to acute or chronic dysfunction in either the heart of kidneys inducing acute or chronic dysfunction of the other organ.

The two senior authors are John Buse, MD, PhD, director of the UNC Diabetes Care Center in Chapel Hill, North Carolina, and Francesco Cosentino, MD, PhD, professor of cardiology at the Karolinska Institute and Karolinska University Hospital in Stockholm, Sweden.

The other authors are Nikolaus Marx, MD, Professor of Internal Medicine at the University Hospital Aachen, Germany; Melanie Davies, MD, Professor in the Diabetes Research Centre at the University of Leicester, Leicester, UK; Peter Grant, MD, Professor of Medicine at the Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds in the UK; Chantal Mathieu, MD, PhD, Clinical and Experimental Endocrinology, Universitair Ziekenhuis Gasthuisberg, Professor of Medicine at Katholieke Universiteit Leuven in Belgium; and John Petrie, MD, PhD, Professor of Medicine at the Institute of Cardiovascular and Medical Sciences, BHF Glasgow Cardiovascular Research Centre in the UK.

The researchers convened to emphasize where commonalities exist and to propose an integrated framework that encompasses the views and approaches proposed by the ESC, the ADA, and EASD.

They wrote in The Lancet: “Coordinated action is required to ensure that people with type 2 diabetes, cardiovascular disease, heart failure, or chronic kidney disease are treated appropriately with an SGLT2 inhibitor or GLP-1 receptor agonist. In our opinion, this course should be initiated independent of background therapy, current glycemic control, or individualized treatment goals.”

First, people with type 2 diabetes and prevalent cardiovascular disease or at high cardiovascular risk should be treated with a GLP­1 receptor agonist or an SGLT2 inhibitor. Second, patients with type 2 diabetes and heart failure should be treated with an SGLT2 inhibitor. Third, patients with type 2 diabetes and chronic kidney disease should be treated with an SGLT2 inhibitor; if this therapy is not tolerated or not preferred, a GLP­1 receptor agonist should be considered. Finally, these treatment decisions should be made independent of background therapy, current glycemic control, or individualized treatment goals. The SGLT2 inhibitor or GLP­1 receptor agonist prescribed should have shown outcome benefit in the relevant clinical trials.

“I am so glad that the American and European cardiologists and diabetes specialists could come together to call for action like this,” said Buse, the Verne S. Caviness Distinguished Professor of at the UNC School of Medicine and Co-Director of the North Carolina Translational and Clinical Sciences (NC TraCS) Institute at UNC Chapel Hill. “These new treatments save lives in patients with diabetes, kidney disease and heart disease, and we should not be quibbling about what drug comes first.”

Matt Cavender, MD, MPH, assistant professor of medicine and co-director of cardiology clinical trials at the UNC Medical Center, who was not an author on the paper, said, “It’s important for providers, regardless of specialty, to all work together to make sure we develop systems of care that ensure patients have access to therapies which are evidence-based and have been shown to reduce cardiovascular events. We need to embrace multidisciplinary care, which is what we have been doing at UNC.”

Media contact: Mark Derewicz, 919-923-0959