The Place and Value of Sodium-Glucose Cotransporter 2 Inhibitors in the Evolving Treatment Paradigm for Type 2 Diabetes Mellitus: A Narrative Review

Abstract

Over recent years, the expanding evidence base for sodium-glucose cotransporter-2 inhibitor (SGLT2i) therapies has revealed benefits beyond their glucose-lowering efficacy in the treatment of Type 2 diabetes mellitus (T2DM), resulting in their recognition as cardiorenal medicines. While SGLT2is continue to be recommended among the second-line therapies for the treatment of hyperglycaemia, their true value now extends to the prevention of debilitating and costly cardiovascular and renal events for high-risk individuals, with particular benefit shown in reducing major adverse cardiac events and heart failure (HF) and slowing the progression of chronic kidney disease. However, SGLT2i usage is still suboptimal among groups considered to be at greatest risk of cardiorenal complications. The ongoing coronavirus disease 2019 (COVID-19) pandemic has intensified financial pressures on healthcare systems, which may hamper further investment in newer effective medicines. Emerging evidence indicates that glycaemic control should be prioritised for people with T2DM in the era of COVID-19 and practical advice on the use of T2DM medications during periods of acute illness remains important, particularly for healthcare professionals working in primary care who face multiple competing priorities. This article provides the latest update from the Improving Diabetes Steering Committee, including perspectives on the value of SGLT2is as cost-effective therapies within the T2DM treatment paradigm, with particular focus on the latest published evidence relating to the prevention or slowing of cardiorenal complications. The implications for ongoing and future approaches to diabetes care are considered in the light of the continuing coronavirus pandemic, and relevant aspects of international treatment guidelines are highlighted with practical advice on the appropriate use of SGLT2is in commonly occurring T2DM clinical scenarios. The ‘SGLT2i Prescribing Tool for T2DM Management’, previously published by the Steering Committee, has been updated to reflect the latest evidence and is provided in the Supplementary Materials to help support clinicians delivering T2DM care. Supplementary Information The online version contains supplementary material available at 10.1007/s13300-022-01228-w.

SGLT2 Inhibitors – The New Standard of Care for Cardiovascular, Renal and Metabolic Protection in Type 2 Diabetes: A Narrative Review

“…Elsewhere, data suggest that HbA1c may be better sustained with combination therapy, compared with stepwise T2DM treatment, and the debate regarding the advantages of intensive blood-glucose management in reducing adverse CV outcomes continues [ 15 , 16 ]. The beneficial properties of oral glucose-lowering drugs in avoiding or decelerating progression toward macrovascular complications have been demonstrated in many studies and are well recognised in the literature and in current NICE, ADA/EASD, Primary Care Diabetes Europe and Kidney Disease: Improving Global Outcomes (KDIGO) guidelines, which advocate early combination therapy incorporating SGLT2is for appropriate individuals [ 3 , 4 , 8 , 9 , 11 , 16 – 39 ]. Diabetes therapy should aim to provide the maximum protection in the minimum time with the relative risks and side effects considered alongside other chronic diseases/comorbidities.…”

“…SGLT2i use has also been typically associated with the lowering of other CV risk factors, such as blood pressure, and recipients often experience weight loss [ 2 , 12 , 17 , 18 , 34 , 35 , 49 , 52 , 53 , 57 – 60 ]. Organ protection remains the cornerstone objective for long-term management of T2DM and the wider implementation of SGLT2is early in the therapeutic pathway would support better outcomes through the lowering of both macrovascular risk and complication severity [ 1 – 4 , 12 , 17 – 23 , 28 , 31 , 35 , 52 , 53 , 56 , 61 ].…”

Abordaje holístico: la clave en el paciente con diabetes mellitus

“…En lo que respecta a los FRCV, actualmente los fármacos que han aportado mayor beneficio son los inhibidores del cotransportador de sodio-glucosa 2 (iSGLT-2) que, además de facilitar el control glucémico, han demostrado reducciones significativas de peso, mejoran la función renal y reducen la tensión arterial de forma moderada 8 .…”

¿Cómo podemos realizar la protección renal del paciente con DM2?

“…[7][8][9][10][11] La elección de un iSGLT-2 debería priorizar los fármacos con beneficios renales o cardiovasculares documentados, teniendo en cuenta el FG, ya que el grado de función renal influye en la eficacia antihiperglucémica, pero no en el beneficio cardiovascular y renal. 12,13 Las fichas técnicas de los iSGLT-2 están actualizándose en función de las evidencias de los estudios que han mostrado beneficio. Por ello es preciso revisar los muy probables cambios en las mismas.…”