Obesity-associated cardiometabolic complications in polycystic ovary syndrome: The potential role of sodium-glucose cotransporter-2 inhibitors

Pruett, Jacob E.; Romero, Damián G.; Cardozo, Licy L. Yanes

doi:10.3389/fendo.2023.951099

Cited by 6 publications

(4 citation statements)

References 141 publications

(215 reference statements)

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“…Previous studies have con rmed the impact of SGLT2 inhibitors on PCOS (19,20). It has been shown that in a high androgenemic PCOS model, the SGLT2 inhibitor empagli ozin (EMPA) has been bene cial for obesity and blood pressure reduction (21).…”

Section: Discussionmentioning

confidence: 99%

Dapagliflozin Attenuates Inflammation and Apoptosis in a Rat Model of Letrozole-Induced Polycystic Ovary Syndrome

Zhang,

Li,

Liu

et al. 2024

Preprint

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Polycystic ovary syndrome (PCOS) is a common endocrine and metabolic disorder related to chronic low-grade inflammation of the ovary. Several women of childbearing age are affected by polycystic ovary syndrome. Sodium-glucose cotransporter-2 (SGLT2) inhibitors are a new class of anti-diabetes drugs that can reduce the weight and hyperglycemia of Type-2 diabetes patients. However, the regulatory role of dapagliflozin, an inhibitor of SGLT2, in PCOS remains unclear. This study randomly divided 24 six-week-old female SD rats into Control, Letrozole, and Letrozole + dapagliflozin groups. PCOS model rats were constructed by gavage of letrozole (1 mg/kg) for 21 days. The intervention was conducted after the gavage of dapagliflozin (10 mg/kg) for 14 days to evaluate the estrous cycle and ovarian imaging changes of rats in each group. In addition, this study observed the weight, ovarian weight, and ovarian morphology changes of rats in each group. The pathological changes of ovaries were examined using H&E staining, the changes of inflammatory-related factors were detected using immunohistochemistry and Western blot, and the changes in apoptosis of ovarian tissue cells were identified using TUNEL staining. Compared with the letrozole group, dapagliflozin treatment significantly improved PCOS symptoms and recovered ovarian morphology and physiological function after drug intervention. Dapagliflozin treatment also reduced ovarian inflammatory factors of IL-1β, IL-6, TNF-α, and NF-κB expression levels and improved the ovary’s apoptosis level. In summary, the treatment with dapagliflozin showed a protective effect on PCOS and reduced the inflammation and apoptosis of the ovary.

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Section: Discussionmentioning

confidence: 99%

Dapagliflozin Attenuates Inflammation and Apoptosis in a Rat Model of Letrozole-Induced Polycystic Ovary Syndrome

Zhang,

Li,

Liu

et al. 2024

Preprint

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“…As SGLT-2 is a sodium-glucose cotransporter, SGLT-2 inhibitors reduce sodium reabsorption in the proximal tubule, 40 which leads to increased sodium delivered to the macula densa, reducing renin release and activating the RAAS. 41 In contrast, some studies have shown that sodium reabsorption is reduced in the proximal tubule and that polyureic natriuretic stimulation induced by SGLT-2 inhibitors activates systemic RAAS in patients with diabetes but does not affect intrarenal RAAS. [42][43][44] Furthermore, no significant changes in plasma aldosterone levels are seen in patients treated with SGLT-2 inhibitors, which may be related to the aldosterone circadian rhythm.…”

Section: Obesity-associated Hypertension Sglt-2 Inhibitors and The Re...mentioning

confidence: 97%

Sodium–Glucose Cotransporter Protein 2 Inhibitors: Novel Application for the Treatment of Obesity-Associated Hypertension

Hu,

Bao,

Gao

et al. 2024

DMSO

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Obesity is becoming increasingly prevalent in China and worldwide and is closely related to the development of hypertension. The pathophysiology of obesity-associated hypertension is complex, including an overactive sympathetic nervous system (SNS), activation of the renin–angiotensin–aldosterone system (RAAS), insulin resistance, hyperleptinemia, renal dysfunction, inflammatory responses, and endothelial function, which complicates treatment. Sodium–glucose cotransporter protein 2 (SGLT-2) inhibitors, novel hypoglycemic agents, have been shown to reduce body weight and blood pressure and may serve as potential novel agents for the treatment of obesity-associated hypertension. This review discusses the beneficial mechanisms of SGLT-2 inhibitors for the treatment of obesity-associated hypertension. SGLT-2 inhibitors can inhibit SNS activity, reduce RAAS activation, ameliorate insulin resistance, reduce leptin secretion, improve renal function, and inhibit inflammatory responses. SGLT-2 inhibitors can, therefore, simultaneously target multiple mechanisms of obesity-associated hypertension and may serve as an effective treatment for obesity-associated hypertension.

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“…Because prior research has shown such tremendous benefits for patients with other medical conditions who are started on an SGLT2 inhibitor, there has been an interest in exploring whether this may be a novel treatment option for patients with PCOS [27][28][29][30]. In this review, we examine the effects of SGLT2 inhibitors on various outcomes in women with polycystic ovary syndrome.…”

Section: Sglt2 Inhibitors In Pcosmentioning

confidence: 99%

The Role of Sodium-Glucose Cotransporter-2 Inhibitors in the Treatment of Polycystic Ovary Syndrome: A Review

Porth,

Oelerich,

Sivanandy

2024

JCM

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Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in reproductive-age women impacting their reproductive, mental, and metabolic health. Insulin resistance is a major driver of the pathophysiology of PCOS. There are several challenges with the management of this complex disorder including insufficient treatment options. Over the past 88 years, multiple hormonal and non-hormonal medications have been tried to treat the various components of this syndrome and there is no FDA (Food and Drug Administration)-approved medication specifically for PCOS yet. Sodium-glucose cotransporter-2 (SGLT-2) inhibitors have a unique mechanism of inhibiting the coupled reabsorption of sodium and glucose in renal proximal convoluted tubules. This review aims to examine the efficacy and side-effect profile of SGLT-2 inhibitors in patients with PCOS. In a limited number of studies, SGLT-2 inhibitors appear to be effective in improving menstrual frequency, reducing body weight and total fat mass, lowering total testosterone and DHEAS levels, and improving some glycemic indices in women with PCOS. SGLT2 inhibitors are generally well tolerated. With future research, it is possible that SGLT-2 inhibitors could become a key therapeutic option for PCOS.

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Obesity-associated cardiometabolic complications in polycystic ovary syndrome: The potential role of sodium-glucose cotransporter-2 inhibitors

Cited by 6 publications

References 141 publications

Dapagliflozin Attenuates Inflammation and Apoptosis in a Rat Model of Letrozole-Induced Polycystic Ovary Syndrome

Dapagliflozin Attenuates Inflammation and Apoptosis in a Rat Model of Letrozole-Induced Polycystic Ovary Syndrome

Sodium–Glucose Cotransporter Protein 2 Inhibitors: Novel Application for the Treatment of Obesity-Associated Hypertension

The Role of Sodium-Glucose Cotransporter-2 Inhibitors in the Treatment of Polycystic Ovary Syndrome: A Review

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