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.

• Keywords
• Cardiorenal protection, Clinical inertia, Glucose lowering drugs, Type 2 diabetes,
• MeSH
• Glucagon-Like Peptide-1 Receptor Agonists MeSH
• Biomarkers blood   MeSH
• Global Health MeSH
• Diabetes Mellitus, Type 2 * blood   diagnosis   drug therapy   epidemiology   MeSH
• Sodium-Glucose Transporter 2 Inhibitors * adverse effects   therapeutic use   MeSH
• Risk Assessment MeSH
• Incretins * adverse effects   therapeutic use   MeSH
• Cardiovascular Diseases * diagnosis   epidemiology   prevention & control   MeSH
• Clinical Decision-Making MeSH
• Blood Glucose * drug effects   metabolism   MeSH
• Practice Patterns, Physicians' MeSH
• Humans MeSH
• Evidence-Based Medicine MeSH
• Kidney Diseases * diagnosis   epidemiology   prevention & control   MeSH
• Protective Factors MeSH
• Glycemic Control * adverse effects   MeSH
• Risk Factors MeSH
• Practice Guidelines as Topic MeSH
• Treatment Outcome MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Glucagon-Like Peptide-1 Receptor Agonists MeSH
• Biomarkers MeSH
• Sodium-Glucose Transporter 2 Inhibitors * MeSH
• GLP1R protein, human MeSH Browser
• Incretins * MeSH
• Blood Glucose * MeSH

BACKGROUND: For patients with type 2 diabetes (T2D), cardiovascular disease (CVD) is the single most common cause of mortality. In 2008 and 2012, the Federal Drug Administration (FDA) and the European Medicines Agency (EMA) respectively mandated cardiovascular outcomes trials (CVOTs) on all new anti-diabetic agents, as prospective trials statistically powered to rule out excess cardiovascular risk in patients with T2D. Unexpectedly, some of these CVOTs have demonstrated not only cardiovascular safety, but also cardioprotective effects, as was first shown for the SGLT2 inhibitor empagliflozin in EMPA-REG OUTCOME. EXPERT OPINION: To debate newly available CVOT data and to put them into context, we convened as a group of medical experts from the Central and Eastern European Region. Here we describe our discussions, focusing on the conclusions we can draw from EMPA-REG OUTCOME and other SGLT2 inhibitor CVOTs, including when considered alongside real-world evidence. CONCLUSION: CVOTs investigating SGLT2 inhibitors have suggested benefits beyond glucose lowering that have been confirmed in real-world evidence studies.

• Keywords
• Canagliflozin, Cardiovascular disease, Dapagliflozin, Empagliflozin, SGLT2 inhibitor, Type 2 diabetes,
• MeSH
• Diabetes Mellitus, Type 2 drug therapy   MeSH
• Sodium-Glucose Transporter 2 Inhibitors adverse effects   MeSH
• Incidence MeSH
• Cardiovascular Diseases epidemiology   etiology   MeSH
• Comorbidity MeSH
• Humans MeSH
• Prognosis MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Sodium-Glucose Transporter 2 Inhibitors MeSH