The Use of SGLT-2 Inhibitors in Type 2 Diabetes and Heart Failure

Abstract

The concurrent management of type 2 diabetes mellitus (T2DM) and chronic congestive heart failure presents several therapeutic challenges. Of concern is that insulin and insulin-sensitizing medications detrimentally "flood" the heart with energy-providing substrates, including fats and glucose. In this population, treatment of T2DM should focus on the reduction of increased substrate supply. Sodium glucose cotransporter-2 (SGLT-2) inhibitors, a new class of antidiabetic medication, operate via this principle by blocking the reabsorption of glucose in the kidney and subsequently releasing glucose through the urine. In this review, we begin with an examination of the mechanisms of glucotoxicity and lipotoxicity in the heart. Then we analyze the potential role of SGLT-2 inhibitor therapy in patients with concurrent T2DM and chronic heart failure. Based on the available evidence, SGLT-2 inhibitors are safe and can be recommended to treat T2DM in patients with chronic heart failure and intact renal function. Further studies are in progress to assess long-term survival benefits.

Clinical Update: Cardiovascular Disease in Diabetes Mellitus

“…373 Possible mechanisms for this observation include osmotic diuresis and reduced arterial stiffness caused by SLGT-2 inhibition leading to lower plasma volume and blood pressure, as well as altering tubular-glomerular feedback mechanisms, 377 or indirect effect on SGLT1, 380 the transporter primarily responsible for intestinal glucose absorption. 477 As with cardiovascular mortality effects, whether this heart failure benefit is a class effect is not yet known and will be evaluated in the ongoing studies Canagliflozin Cardiovascular Assessment Study (NCT01032629) and Multicenter Trial to Evaluate the Effect of Dapagliflozin on the Incidence of Cardiovascular Events (NCT01730534).…”

The potential role and rationale for treatment of heart failure with sodium–glucose co‐transporter 2 inhibitors

“…This occurs rapidly initially and then gradually until a plateau is reached and it is sustained over time. The initial decline is thought to occur as a result of osmotic diuresis; however, the subsequent gradual and predominant weight reduction is likely caused by caloric urinary glucose loss resulting in a reduction in visceral fat mass . There is ample evidence that obesity per se is a strong risk factor for incident HF but whether weight loss and the method of weight loss influence outcomes in patients with manifest HF, or those with diabetes, remains controversial.…”

Precision Medicine for Heart Failure with Preserved Ejection Fraction: An Overview

“…Furthermore, the majority of pheno-group #2 patients have a very high BMI (> 35 kg/m 2 ) and thus may also suffer from the obesity HFpEF phenotype described above. Based on the aforementioned pathophysiology, pheno-group #2 patients may respond best to drugs that target microvascular dysfunction or the cardiometabolic phenotype (e.g., SGLT-2 inhibitors [56]) or even medical or surgical weight loss strategies. Theoretically, controlling blood pressure would also help these patients; however, thus far reducing blood pressure has not led to major improvements in outcomes in HFpEF patients based on trials of angiotensin receptor blockers and angiotensin converting enzyme inhibitors.…”