SGLT2 inhibitors in hypertension: Role beyond diabetes and heart failure

Gupta, Rahul; Maitz, Theresa; Egeler, David; Mehta, Anila; Nyaeme, Mark; Hajra, Adrija; Goel, Akshay; Sreenivasan, Jayakumar; Patel, Neelkumar; Aronow, Wilbert S.

doi:10.1016/j.tcm.2022.05.005

Cited by 12 publications

(9 citation statements)

References 46 publications

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“…Additionally, the effect was comparable to conventional antihypertensive monotherapies [50]. Empagliflozin has a clinically relevant reduction in blood pressure [51,52]. The cardiorenal effects of SGLT2i differ depending on race.…”

Section: Sglt2 Inhibitors Have a Secondary Effect On Blood Pressurementioning

confidence: 84%

The relationship between SGLT2 and systemic blood pressure regulation

Ahwin,

Martinez

2024

Hypertens Res

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The sodium-glucose cotransporter 2 (SGLT2) is a glucose transporter that is located within the proximal tubule of the kidney’s nephrons. While it is typically associated with the kidney, it was later identified in various areas of the central nervous system, including areas modulating cardiorespiratory regulation like blood pressure. In the kidney, SGLT2 functions by reabsorbing glucose from the nephron’s tubule into the bloodstream. SGLT2 inhibitors are medications that hinder the function of SGLT2, thus preventing the absorption of glucose and allowing for its excretion through the urine. While SGLT2 inhibitors are not the first-line choice, they are given in conjunction with other pharmaceutical interventions to manage hyperglycemia in individuals with diabetes mellitus. SGLT2 inhibitors also have a surprising secondary effect of decreasing blood pressure independent of blood glucose levels. The implication of SGLT2 inhibitors in lowering blood pressure and its presence in the central nervous system brings to question the role of SGLT2 in the brain. Here, we evaluate and review the function of SGLT2, SGLT2 inhibitors, their role in blood pressure control, the future of SGLT2 inhibitors as antihypertensive agents, and the possible mechanisms of SGLT2 blood pressure control in the central nervous system.

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Section: Sglt2 Inhibitors Have a Secondary Effect On Blood Pressurementioning

confidence: 84%

The relationship between SGLT2 and systemic blood pressure regulation

Ahwin,

Martinez

2024

Hypertens Res

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“…[ 14 ] SGLT2is are kind of drugs that lowering the blood glucose levels by hastening glycosuria. SGLT2i exert many systematic roles beyond lowering blood glucose, such as hypertension, [ 15 ] hepatocellular carcinoma, [ 16 ] cardiovascular disease, [ 17 ] cognitive function. [ 18 ] Meantime SGLT2i have important roles in aging process.…”

Section: Discussionmentioning

confidence: 99%

The Comparation of Renal Anti‐Senescence Effects and Blood Metabolites between Dapagliflozin and Metformin in Non‐Diabetes Environment

Zeng,

Chen,

Gao

et al. 2023

Advanced Biology

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Delaying kidney senescence process will benefit renal physiologic conditions, and prompt the kidney recovering from different pathological states. The renal anti‐senescence effects of sodium‐glucose cotransporter‐2 inhibitors (SGLT2i) and metformin have been proven in diabetic settings, but the roles of each one and combination of two drugs in natural kidney aging process remain undefined and deserve further research. Senescence‐accelerated mouse prone 8 (SAMP8) were orally administered dapagliflozin, metformin, and a combination of them for 16 weeks. Dapagliflozin exhibits better effects than metformin in lowering senescence related markers, and the combination therapy shows the best results. In vitro experiments demonstrate the same results that the combination of dapagliflozin and metformin can exert a better anti‐senescence effect. Blood metabolites detection in vivo shows dapagliflozin mainly leads to the change of blood metabolites enriched in choline metabolism, and metformin tends to induce change of blood metabolites enriched in purine metabolism. In conclusion, the results suggest dapagliflozin may have a better renal anti‐senescence effect than metformin in non‐diabetes environment, and the combination of the two drugs can strengthen the effect. The two drugs can lead to different blood metabolites alteration, which may lead to different systemic effects.

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“…Other side effects were suggested to be associated with SGLT2i as bone fractures, amputations, and malignancies, but results are controversial [88].…”

Section: Sglt2i Side Effectsmentioning

confidence: 99%

Sodium-Glucose Co-Transporter 2 Inhibitors: Mechanism of Action and Efficacy in Non-Diabetic Kidney Disease from Bench to Bed-Side

Abdelrahman,

Awad,

Abdel-Rahman

2024

JCM

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Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are currently available for the management of type 2 diabetes mellitus. SGLT2i acts by inhibiting renal SGLT2, thereby increasing glucosuria and lowering serum glucose. Recent trials are emerging supporting a role for SGLT2i irrespective of the diabetic status pointing towards that SGLT2i have other mechanisms of actions beyond blood sugar control. In this review, we will shed light on the role of this group of medications that act as SGLT2i in non-diabetics focusing on pre-clinical and clinical data highlighting the mechanism of renoprotection and effects of SGLT2i in the non-diabetic kidneys.

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SGLT2 inhibitors in hypertension: Role beyond diabetes and heart failure

Cited by 12 publications

References 46 publications

The relationship between SGLT2 and systemic blood pressure regulation

The relationship between SGLT2 and systemic blood pressure regulation

The Comparation of Renal Anti‐Senescence Effects and Blood Metabolites between Dapagliflozin and Metformin in Non‐Diabetes Environment

Sodium-Glucose Co-Transporter 2 Inhibitors: Mechanism of Action and Efficacy in Non-Diabetic Kidney Disease from Bench to Bed-Side

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