What Makes Sodium-Glucose Co-Transporter-2 Inhibitors Stand out in Heart Failure?
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MACROVASCULAR COMPLICATIONS IN DIABETES (VR ARODA AND L-S CHANG, SECTION EDITORS)
What Makes Sodium-Glucose Co-Transporter-2 Inhibitors Stand out in Heart Failure? Muhammad Shahzeb Khan 1 & Muthiah Vaduganathan 2 Accepted: 10 September 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Purpose of Review We highlight the unique properties of the sodium-glucose cotransporter-2 (SGLT-2 inhibitors) which may lend favorably to their efficient integration in the background of other heart failure (HF) therapies. We also discuss the unique aspects of SGLT-2 inhibitor dosing, lack of titration needs, effects on kidney function and electrolytes, diuretic activity, and safety in the high-risk peri-hospitalization window. Recent Findings Dapagliflozin was recently approved for the treatment of heart failure with reduced ejection fraction (HFrEF), irrespective of the presence or absence of type 2 diabetes mellitus (T2DM) based on the findings of the pivotal DAPA-HF trial. All SGLT-2 inhibitors are once daily medications with minimal drug-drug interactions and do not require titration (for HF treatment) unlike other HF medications. SGLT-2 inhibitors offer modest weight loss and blood pressure reduction without major adverse effects of hyperkalemia, making it ideal for near-simultaneous initiation with other HF medications, and use in high-risk populations (including older adults). Moreover, SGLT-2 inhibitors appear to afford long-term kidney protection in diverse populations. Summary SGLT-2 inhibitors are the latest class of therapies to demonstrate important clinical benefits among patients with HFrEF, and their pharmacological properties favor ease of use and integration in multi-drug disease-modifying regimens. Keywords Antihyperglycemic therapies . Diabetes mellitus . Heart failure . SGLT-2 inhibitors
Introduction There are approximately 500 million patients with type 2 diabetes mellitus (T2DM) and 64 million patients with heart failure (HF) globally [1, 2]. T2DM and HF often co-exist with one causing a worse prognosis in the other [3, 4]. Antihyperglycemic therapies such as thiazolidinediones and saxagliptin may increase HF events and thus are discouraged among patients with established HF [5, 6]. Other therapies This article is part of the Topical Collection on Macrovascular Complications in Diabetes * Muthiah Vaduganathan [email protected] 1
Department of Medicine, Cook County Health and Hospital System, Chicago, IL, USA
2
Heart and Vascular Center, Brigham and Women’s Hospital Heart & Vascular Center and Harvard Medical School, 75 Francis St, Boston, MA 02115, USA
such as the glucagon-like peptide-1 receptor agonists (GLP1 RA) appear to primarily target atherosclerotic disease pathways while minimally altering pathways that affect HF events. The sodium-glucose cotransporter-2 (SGLT2) inhibitors have been shown to reduce risk of HF events among various at-risk populations with T2DM (Table 1) [7–9, 10••]. SGLT-2 inhibitors block reabsorption of filtered glucose in the prox
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