SGLT2 Inhibitors: Cardiovascular Benefits Beyond HbA1c—Translating Evidence into Practice

Abstract

Cardiovascular disease (CVD), including heart failure (HF), is a leading cause of morbidity and mortality in people with type 2 diabetes mellitus (T2DM). CVD and T2DM share common risk factors for development and progression, and there is significant overlap between the conditions in terms of worsening outcomes. In assessing the cardiovascular (CV) safety profiles of anti-diabetic drugs, sodium-glucose cotransporter-2 inhibitor (SGLT2i) therapies have emerged with robust evidence for reducing the risk of adverse CVD outcomes in people with T2DM who have either established CVD or are at risk of developing CVD. A previous consensus document from the Improving Diabetes Steering Committee has examined the potential role of SGLT2is in T2DM management and considered the risk-benefit profile of the class and the appropriate place for these medicines within the T2DM pathway. This paper builds on these findings and presents practical guidance for maximising the pleiotropic benefits of this class of medicines in people with T2DM in terms of Enhanced Digital Features To view enhanced digital features for this article go to https://doi.org/10.6084/ m9.figshare.8276270.

Renal Outcomes in Type 2 Diabetes: A Review of Cardiovascular and Renal Outcome Trials

“…The administration of empagliflozin attenuated renal hyperfiltration in participants with eGFR [ 135 ml/min/ 1.73 m 2 and did not alter renal function in those with a normal eGFR. This important observation highlights that SGLT-2 inhibitors can influence the glomerular hyperfiltration that characterises the earlier stages of diabetic nephropathy, thereby lessening its progression [12,15,16].…”

“…The consequent increased urinary excretion of glucose is responsible for the improved glycaemia and weight loss. Moreover, the reduced tubular reabsorption of sodium and glucose promotes natriuresis, reducing blood pressure [11,12]. One meta-analysis reported significant reductions in the progression of albuminuria, the risk of worsening renal impairment, the need for a renal transplant, and death from a renal cause [13].…”

“…In mouse models at least, production of these proinflammatory cytokines is attenuated by the administration of SGLT-2 inhibitors such as dapagliflozin or empagliflozin, leading to reduced glomerulosclerosis and tubulointerstitial fibrosis [17,18]. These drugs also preserve renal function by addressing risk factors for renal disease: they reduce blood pressure and improve hyperglycaemia and weight loss [12,16]. The combined effect of stabilising the GFR, reduced tubulointerstitial fibrosis and improved risk factors for renal disease explains the reduced incidence and progression of albuminuria in people with diabetes who are using SGLT-2 inhibitors.…”

Drug Therapy in Obesity: A Review of Current and Emerging Treatments

“…Sodium-glucose co-transporter-2 (SGLT-2) inhibitors are currently licensed for the treatment of T2D, though there is a growing body of evidence to support their use in cardiovascular [56] and renal disease [57]. These drugs block the SGLT-2 protein in the proximal convoluted tubule, thereby inducing a glucose-mediated osmotic diuresis and natriuresis, improving several metabolic measures [58].…”

SGLT2 Inhibitors: Slowing of Chronic Kidney Disease Progression in Type 2 Diabetes

“…The group is committed to providing healthcare colleagues with clarity regarding the evidence base supporting SGLT2i agents, highlighting the relative benefits and risks of these therapies. Educational materials and publications, such as the previously published consensus documents, provided by the panel are intended to increase confidence and understanding regarding the appropriate place of these medicines within the current UK T2DM treatment paradigm [1,2]. Professor David Wheeler was involved with the planning, delivery, analysis and publication of the CREDENCE study, which included human participants and complied with the tenets of the Declaration of Helsinki.…”