Sodium-glucose Cotransporter 2 Inhibitors: The Pleiotropic Mechanisms of Actions

Pantelidis, Panteleimon; Kalliakmanis, Andreas; Mitas, Christos; Sideris, Michail; Grassos, Charalampos; Pittaras, Andreas; Manolis, Athanasios

doi:10.2174/1871529x18666180206130218

Cited by 4 publications

(2 citation statements)

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“…The mechanisms that contribute to the beneficial effects of SGLT2i and GLP-1RAs in patients with T2DM have been extensively studied. ( Figure 5 ) Briefly, SGLT2i inhibits the SGLT receptors in the proximal tubule, which inhibits the reabsorption of glucose from primary urine, resulting in glycosuria and a decrease in HbA1c and fasting glucose levels ( 29 ). The hypoglycemic effects of SGLT2i do not rely on insulin secretion, which minimizes the risk of hypoglycemia.…”

Section: Discussionmentioning

confidence: 99%

First-line treatment with sodium-glucose cotransporter 2 inhibitors and glucagon-like peptide-1 receptor agonists in type 2 diabetic population at low risk of cardiovascular disease: a meta-analysis

Deng,

Mei,

Song

et al. 2024

Front. Endocrinol.

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BackgroundThe benefit of first-line use of sodium-dependent glucose transport 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1RAs) in type 2 diabetes mellitus (T2DM) with low risk of cardiovascular diseases are not clear.MethodsPubMed, EMBASE and Cochrane Library databases were searched to identify eligible randomized controlled trials. We used the odds ratio (OR) and mean difference (MD) and the corresponding 95% confidence interval (CI) to assess the dichotomous and continuous variable, respectively.ResultsThirteen studies involving 2,885 T2DM at low risk of cardiovascular diseases were included. Compared to placebo, first line use of SGLT2i significantly reduced glycosylated hemoglobin type A1C (HbA1c) (MD: -0.72), weight (MD: -1.32) and fasting plasma glucose (FPG) (MD: -27.05) levels. Compared with metformin, SGLT2i reduced body weight (MD: -1.50) and FPG (MD: -10.13) more effectively, with similar reduction for HbA1c (MD: -0.05). No significant increased safety adverse was found for SGLT2i, including nasopharyngitis (OR: 1.07), urinary tract infection (OR: 2.31), diarrhea (OR: 1.18) and hypoglycemia (OR: 1.06). GLP-1RAs significantly reduced HbA1c (MD: -1.13), weight (MD: -2.12) and FPG (MD: -31.44) levels as first-line therapy compared to placebo. GLP-1RAs significantly increased occurrence of diarrhea (OR: 2.18), hypoglycemia (OR: 3.10), vomiting (OR: 8.22), and nausea (OR: 4.41).ConclusionFirst line use of SGLT2i and GLP-1RAs is effective in reducing HbA1c, weight, and FPG levels in T2DM patients at low risk for cardiovascular disease. SGLT2i may be superior to metformin in controlling body weight and FPG. GLP-1RAs may increase the occurrence of diarrhea, hypoglycemia, vomiting, and nausea.Systematic review registrationPROSPERO (International Prospective Register of Systematic Reviews. https://www.york.ac.uk/inst/crd, CRD42022347233).

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Section: Discussionmentioning

confidence: 99%

First-line treatment with sodium-glucose cotransporter 2 inhibitors and glucagon-like peptide-1 receptor agonists in type 2 diabetic population at low risk of cardiovascular disease: a meta-analysis

Deng,

Mei,

Song

et al. 2024

Front. Endocrinol.

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“…Furthermore, the relative risk for CV events in patients with DM is two to four times higher than that in patients without DM [ 3 ]. Sodium-glucose cotransporter (SGLT) 2 inhibitors are widely used anti-diabetic drugs that increase urinary glucose excretion [ 4 ]. In addition to their hypoglycemic effects, SGLT2 inhibitors have cardioprotective effects although the underlying mechanism is unclear.…”

Section: Introductionmentioning

confidence: 99%

Cardioprotective Effects of Sodium-Glucose Cotransporter Subtype Inhibition on Ischemic and Pharmacological Preconditioning

Egashira,

Ichinomiya,

Yokoyama

et al. 2024

Cureus

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Background: Sodium-glucose cotransporter (SGLT) 2 inhibitors partially inhibit SGLT1 expression; however, whether a clinical dose of SGLT2 inhibitor abrogates ischemic preconditioning (IPC) is unknown, and the pharmacological cardioprotective effect under SGLT1 inhibition has not been examined. In this study, we investigated whether a clinical dose of tofogliflozin abrogates IPC and whether pharmacological preconditioning with olprinone has cardioprotective effects under SGLT1 inhibition.Methods: Male Wistar rats were divided into seven groups (seven rats per group) and subjected to the following treatments before inducing ischemia/reperfusion (I/R; 30 minutes of coronary artery occlusion followed by 120 minutes of reperfusion): saline infusion control treatment (Con); ischemic preconditioning (IPC); IPC after phlorizin infusion (IPC+Phl); IPC after low-dose tofogliflozin infusion (IPC+L-Tof); IPC after high-dose tofogliflozin infusion (IPC+H-Tof); olprinone infusion (Olp); and Olp infusion after phlorizin infusion (Olp+Phl).Results: The infarct size was significantly decreased in the IPC group, but not in the IPC+Phl group. In contrast, the infarct size decreased in the IPC+L-Tof and IPC+H-Tof groups. Additionally, Olp reduced the infarct size, and the effect was preserved in Olp+Phl groups. Phosphorylated AMP-activated protein kinase (AMPK) expression was lower in the IPC+Phl group compared to that in the IPC group. Conclusion:The cardioprotective effect of IPC was attenuated by strong SGLT1 inhibition, but the effect was preserved under a clinical dose of highly selective SGLT2 inhibitor. Olprinone exerts a cardioprotective effect even under strong SGLT1 inhibition.

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Understanding the cardiovascular risk with non-insulin antidiabetic drugs

Athyros

Imprialos

Stavropoulos

et al. 2019

Expert Opinion on Drug Safety

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Sodium-glucose Cotransporter 2 Inhibitors: The Pleiotropic Mechanisms of Actions

Cited by 4 publications

References 0 publications

First-line treatment with sodium-glucose cotransporter 2 inhibitors and glucagon-like peptide-1 receptor agonists in type 2 diabetic population at low risk of cardiovascular disease: a meta-analysis

First-line treatment with sodium-glucose cotransporter 2 inhibitors and glucagon-like peptide-1 receptor agonists in type 2 diabetic population at low risk of cardiovascular disease: a meta-analysis

Cardioprotective Effects of Sodium-Glucose Cotransporter Subtype Inhibition on Ischemic and Pharmacological Preconditioning

Understanding the cardiovascular risk with non-insulin antidiabetic drugs

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