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Are SGLT2 Inhibitors Reasonable Antihypertensive Drugs and Renoprotective?

  • Therapeutic Trials (M Weir, Section Editor)
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Abstract

By eliminating glucose in the urine, the sodium-glucose-linked cotransporter-2 (SGLT2) inhibitors act as osmotic diuretics to lower blood pressure in addition to reducing plasma glucose and assisting with weight loss. While not approved as antihypertensive agents, the ability of this new class of antihyperglycemic agents to lower blood pressure is not insubstantial, and while not used primarily for this indication, they may assist diabetic individuals in attaining currently recommended blood pressure targets. In addition to lowering systemic pressure, preclinical and exploratory human studies suggest that SGLT2 inhibitors may also lower intraglomerular pressure, potentially reducing the rate of GFR decline in patients with diabetic nephropathy. However, given the lack of clinically meaningful endpoint data, the use of SGLT2 inhibitors, primarily, as either antihypertensive or renoprotective agents would, at present, be premature. Fortunately, further insight will be garnered from large, randomized controlled trials that will assess the effects of various SGLT2 inhibitors on cardiovascular and renal outcomes.

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Abbreviations

ABPM:

Ambulatory blood pressure monitoring

ACR:

Albumin/creatinine ratio

ACE:

Angiotensin converting enzyme

ARB:

Angiotensin receptor blocker

CKD:

Chronic kidney disease

FDA:

Federal Drug Agency (US)

eGFR:

Estimated glomerular filtration rate

EMA:

European Medicines Agency (European Union)

GFR:

Glomerular filtration rate

HCTZ:

Hydrochlorothiazide

JGA:

Juxtaglomerular apparatus

NNH:

Number needed to harm

RCTs:

Randomized controlled trials

SGLT1:

Sodium-glucose-linked cotransporter-1

SGLT2:

Sodium-glucose-linked cotransporter-2

SNGFR:

Single nephron glomerular filtration rate

RAS:

Renin-angiotensin system

TGF:

Tubuloglomerular Feedback

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Conflict of Interest

R.E. Gilbert reports grants to his institution, membership on advisory boards and honoraria for CME events from Astra Zeneca, membership on advisory boards and honoraria for CME events from Janssen, membership on advisory boards and honoraria for CME events from Boehringer Ingelheim. J.A. Lovshin declares no conflict of interest.

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This article does not contain any studies with human or animal subjects performed by any of the authors.

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  1. Mt. Sinai Hospital, Division of Endocrinology and Metabolism, University of Toronto, Toronto, ON, Canada

    J. A. Lovshin

  2. Keenan Research Centre, Li Ka Shing Knowledge Institute, St. Michael’s Hospital, Toronto, ON, Canada

    R. E. Gilbert

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Correspondence to J. A. Lovshin.

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Lovshin, J.A., Gilbert, R.E. Are SGLT2 Inhibitors Reasonable Antihypertensive Drugs and Renoprotective?. Curr Hypertens Rep 17, 40 (2015). https://doi.org/10.1007/s11906-015-0551-3

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