Molecular mechanisms by which SGLT2 inhibitors can induce insulin sensitivity in diabetic milieu: A mechanistic review

Yaribeygi, Habib; Sathyapalan, Thozhukat; Maleki, Mina; Jamialahmadi, Tannaz; Sahebkar, Amirhossein

doi:10.1016/j.lfs.2019.117090

Cited by 66 publications

(62 citation statements)

References 102 publications

(175 reference statements)

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“… 82 In addition to their glucose-lowering effect, they can also improve insulin sensitivity via several molecular pathways including reduction of glucotoxicity and lipotoxicity, enhance β-cells function, reduce the oxidative damage and inflammatory processes, improve caloric deposition and weight loss. 83 …”

Section: Treatment Options For Managing Metabolic Comorbiditiesmentioning

confidence: 99%

A review of therapeutic options for managing the metabolic aspects of polycystic ovary syndrome

Abdalla

Deshmukh

Atkin

et al. 2020

Therapeutic Advances in Endocrinology

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Polycystic ovary syndrome (PCOS) is a common endocrine disorder in women of reproductive age. Metabolic sequelae associated with PCOS range from insulin resistance to type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD). Insulin resistance plays a significant role in the pathophysiology of PCOS and it is a reliable marker for cardiometabolic risk. Although insulin sensitising agents such as metformin have been traditionally used for managing metabolic aspects of PCOS, their efficacy is low in terms of weight reduction and cardiovascular risk reduction compared with newer agents such as incretin mimetics and SGLT2 inhibitors. With current pharmaceutical advances, potential therapeutic options have increased, giving patients and clinicians more choices. Incretin mimetics are a promising therapy with a unique metabolic target that could be used widely in the management of PCOS. Likewise, bariatric procedures have become less invasive and result in effective weight loss and the reversal of metabolic morbidities in some patients. Therefore, surgical treatment targeting weight loss becomes increasingly common in the management of obese women with PCOS. Newer emerging therapies, including twincretins, triple GLP-1 agonists, glucagon receptor antagonists and imeglemin, are promising therapeutic options for treating T2DM. Given the similarity of metabolic and pathological features between PCOS and T2DM and the variety of therapeutic options, there is the potential to widen our strategy for treating metabolic disorders in PCOS in parallel with current therapeutic advances. The review was conducted in line with the recommendations from the international evidence-based guideline for the assessment and management of polycystic ovary syndrome 2018.

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Section: Treatment Options For Managing Metabolic Comorbiditiesmentioning

confidence: 99%

A review of therapeutic options for managing the metabolic aspects of polycystic ovary syndrome

Abdalla

Deshmukh

Atkin

et al. 2020

Therapeutic Advances in Endocrinology

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“…SGLT 2 inhibitors, such as dapagliflozin and empagliflozin, decrease renal glucose reabsorption, resulting in enhanced urinary glucose excretion and subsequent reductions in plasma glucose and glycosylated hemoglobin concentrations( Nauck, 2014 ). SGLT2 inhibitors could improve insulin sensitivity and glucose homeostasis via reducing glucotoxicity, improving β cell function, reducing oxidative damages and inflammatory processes and inducing caloric disposition and weight loss( Yaribeygi et al, 2020 ). Dapagliflozin could improve brain insulin sensitivity, alleviate brain mitochondrial dysfunction, attenuate brain apoptosis and brain inflammation, and preserve hippocampal synaptic plasticity( Sa-nguanmoo et al, 2017 ).…”

Section: Repurposing Of Anti-diabetic Agents As a Potential Treatmentmentioning

confidence: 99%

Repurposing of Anti-Diabetic Agents as a New Opportunity to Alleviate Cognitive Impairment in Neurodegenerative and Neuropsychiatric Disorders

Chen

Cao

et al. 2021

Front. Pharmacol.

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Cognitive impairment is a shared abnormality between type 2 diabetes mellitus (T2DM) and many neurodegenerative and neuropsychiatric disorders, such as Alzheimer’s disease (AD) and schizophrenia. Emerging evidence suggests that brain insulin resistance plays a significant role in cognitive deficits, which provides the possibility of anti-diabetic agents repositioning to alleviate cognitive deficits. Both preclinical and clinical studies have evaluated the potential cognitive enhancement effects of anti-diabetic agents targeting the insulin pathway. Repurposing of anti-diabetic agents is considered to be promising for cognitive deficits prevention or control in these neurodegenerative and neuropsychiatric disorders. This article reviewed the possible relationship between brain insulin resistance and cognitive deficits. In addition, promising therapeutic interventions, especially current advances in anti-diabetic agents targeting the insulin pathway to alleviate cognitive impairment in AD and schizophrenia were also summarized.

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“…is process does not depend on insulin resistance and β-cell function [20]. Recent studies have shown that in addition to lowering blood glucose, the SGLT2 inhibitor dapagliflozin…”

Section: Discussionmentioning

confidence: 99%

“…SGLT2 inhibitors, which act independently of insulin, selectively inhibit SGLT2 in the kidney and block the reabsorption of glucose, thereby lowering blood glucose levels. This process does not depend on insulin resistance and β -cell function [ 20 ]. Recent studies have shown that in addition to lowering blood glucose, the SGLT2 inhibitor dapagliflozin also has a positive effect on patients with heart failure [ 10 – 12 , 21 – 23 ].…”

Section: Discussionmentioning

confidence: 99%

Dapagliflozin in Patients with Chronic Heart Failure: A Systematic Review and Meta-Analysis

Cai

2021

Cardiology Research and Practice

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Sodium-glucose cotransporter-2 (SGLT2) inhibitors represent newly developed oral antidiabetic drugs that are practiced for type 2 diabetes mellitus management and may decrease the risk of the first hospitalization in heart failure. The activity of SGLT2 inhibitors is not related to glucose, and the effectiveness and safety of SGLT2 inhibitors in individuals with chronic heart failure (CHF) remain unclear. We systematically retrieved PubMed, Cochrane Library, Embase, NCKI, VIP, Wanfang Data, and ClinicalTrials.gov records to identify eligible trials. The primary endpoints were cardiovascular death/hospitalization for heart failure (CV death/HHF), cardiovascular death, and hospitalization for heart failure. Secondary endpoints included hypoglycemia, volume depletion, urinary tract infection, left ventricular ejection fraction (LVEF), and NT-proBNP. Nine randomized controlled clinical trials were included. Dapagliflozin was reported to significantly decrease CV death/HHF (relative risk (RR): 0.75; 95% confidence interval (CI): 0.68–0.84), CV death (RR: 0.80; 95% CI: 0.68–0.93), and HHF (RR: 0.72; 95% CI: 0.63–0.83). There was no effect on hypoglycemia (RR: 0.69; 95% CI: 0.34–1.40), volume depletion (RR: 1.17; 95% CI: 0.97–1.41), urinary tract infection (RR: 0.82; 95% CI: 0.43–1.57), LVEF (WMD: 0.53; 95% CI: −4.04–5.09), or NT-proBNP (SMD: −0.66; 95% CI: −1.42–0.10). The risk of CV death/HHF, CV death, and HHF was lower among patients receiving dapagliflozin than patients receiving placebo.

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Molecular mechanisms by which SGLT2 inhibitors can induce insulin sensitivity in diabetic milieu: A mechanistic review

Cited by 66 publications

References 102 publications

A review of therapeutic options for managing the metabolic aspects of polycystic ovary syndrome

A review of therapeutic options for managing the metabolic aspects of polycystic ovary syndrome

Repurposing of Anti-Diabetic Agents as a New Opportunity to Alleviate Cognitive Impairment in Neurodegenerative and Neuropsychiatric Disorders

Dapagliflozin in Patients with Chronic Heart Failure: A Systematic Review and Meta-Analysis

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