SGLT inhibitors as antidiabetic agents: a comprehensive review

Kshirsagar, Rahul Padmakar; Kulkarni, Abhishek; Chouthe, Rashmi S.; Pathan, Shahebaaz K.; Une, Hemant D.; Reddy, G. Bhanuprakash; Diwan, Prakash V.; Ansari, Siddique Akber; Sangshetti, Jaiprakash N.

doi:10.1039/c9ra08706k

Cited by 24 publications

(11 citation statements)

References 160 publications

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“…By selectively inhibiting renal glucose reabsorption, SGLT2-Is (also called gliflozins) have emerged in the last decade as glucose-lowering drugs, producing appreciable improvements to glycemic control through a mechanism of action totally independent from insulin and related to the glucose amount that is filtered daily by the glomerulus, reaching the proximal tubule [ 249 ]. As largely demonstrated, SGLT2-Is produce a reduction in HbA1c of 7–10 mmol/mol (0.6–0.9%) in diabetic subjects without determining hypoglycemia.…”

Section: Sglt2 Inhibitors (Sglt2-is)mentioning

confidence: 99%

Coronary Microvascular Dysfunction in Diabetes Mellitus: Pathogenetic Mechanisms and Potential Therapeutic Options

et al. 2022

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Diabetic patients are frequently affected by coronary microvascular dysfunction (CMD), a condition consisting of a combination of altered vasomotion and long-term structural change to coronary arterioles leading to impaired regulation of blood flow in response to changing cardiomyocyte oxygen requirements. The pathogenesis of this microvascular complication is complex and not completely known, involving several alterations among which hyperglycemia and insulin resistance play particularly central roles leading to oxidative stress, inflammatory activation and altered barrier function of endothelium. CMD significantly contributes to cardiac events such as angina or infarction without obstructive coronary artery disease, as well as heart failure, especially the phenotype associated with preserved ejection fraction, which greatly impact cardiovascular (CV) prognosis. To date, no treatments specifically target this vascular damage, but recent experimental studies and some clinical investigations have produced data in favor of potential beneficial effects on coronary micro vessels caused by two classes of glucose-lowering drugs: glucagon-like peptide 1 (GLP-1)-based therapy and inhibitors of sodium-glucose cotransporter-2 (SGLT2). The purpose of this review is to describe pathophysiological mechanisms, clinical manifestations of CMD with particular reference to diabetes, and to summarize the protective effects of antidiabetic drugs on the myocardial microvascular compartment.

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Section: Sglt2 Inhibitors (Sglt2-is)mentioning

confidence: 99%

Coronary Microvascular Dysfunction in Diabetes Mellitus: Pathogenetic Mechanisms and Potential Therapeutic Options

et al. 2022

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“…2 A plethora of C-aryl glycosides are found in nature and serve as key substrates in various biological mechanisms or are used as antitumor, 3 antibiotic, 4 and type II antidiabetic agents (Figure 1). 5 As an example, pseudouridine is the first modified C-nucleoside 6 discovered in RNAs of living organisms. Different classes of RNAs are subject to pseudouridylation such as tRNAs, ribosomal RNAs, and small nuclear RNAs.…”

Section: Introductionmentioning

confidence: 99%

Diastereoselective Pd-Catalyzed Anomeric C(sp³)–H Activation: Synthesis of α-(Hetero)aryl C-Glycosides

et al. 2021

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Anomeric C-H bond activation is an unsolved long-standing synthetic challenge. Herein we report a diastereoselective Pd-catalyzed anomeric C(sp 3 )-H activation methodology that allows the synthesis of elusive C-(hetero)arylglycosides with an exclusive α-selectivity.a Reactions were performed an oven dried re-sealable tube using sugar 1a (0.1 mmol), ArX 2 (3 equiv), Pd(OAc)2 (0.01 mmol), Ag2CO3 (3 equiv) in tAmOH (1.0 mL) at 120 °C. b Yield of isolated product.

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“…Phlorizin, binding the extracellular surface of SGLT1 and SGLT2 in the presence of Na + , inhibits proteins in a reversible, competitive way ( 31 ). However, caused of its poor solubility in water and low absorption in the gastrointestinal tract, several molecules with a similar structure were subsequently developed ( 32 ).…”

Section: Sglt2 Inhibitorsmentioning

confidence: 99%

Anti-inflammatory role of SGLT2 inhibitors as part of their anti-atherosclerotic activity: Data from basic science and clinical trials

Cataldo

Taktaz

Fontanella

et al. 2022

Front. Cardiovasc. Med.

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Atherosclerosis is a progressive inflammatory disease leading to mortality and morbidity in the civilized world. Atherosclerosis manifests as an accumulation of plaques in the intimal layer of the arterial wall that, by its subsequent erosion or rupture, triggers cardiovascular diseases. Diabetes mellitus is a well-known risk factor for atherosclerosis. Indeed, Type 2 diabetes mellitus patients have an increased risk of atherosclerosis and its associated-cardiovascular complications than non-diabetic patients. Sodium-glucose co-transport 2 inhibitors (SGLT2i), a novel anti-diabetic drugs, have a surprising advantage in cardiovascular effects, such as reducing cardiovascular death in a patient with or without diabetes. Numerous studies have shown that atherosclerosis is due to a significant inflammatory burden and that SGLT2i may play a role in inflammation. In fact, several experiment results have demonstrated that SGLT2i, with suppression of inflammatory mechanism, slows the progression of atherosclerosis. Therefore, SGLT2i may have a double benefit in terms of glycemic control and control of the atherosclerotic process at a myocardial and vascular level. This review elaborates on the anti-inflammatory effects of sodium-glucose co-transporter 2 inhibitors on atherosclerosis.

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SGLT inhibitors as antidiabetic agents: a comprehensive review

Abstract: Diabetes is one of the most common disorders that substantially contributes to an increase in global health burden.

Cited by 24 publications

References 160 publications

Coronary Microvascular Dysfunction in Diabetes Mellitus: Pathogenetic Mechanisms and Potential Therapeutic Options

Coronary Microvascular Dysfunction in Diabetes Mellitus: Pathogenetic Mechanisms and Potential Therapeutic Options

Diastereoselective Pd-Catalyzed Anomeric C(sp³)–H Activation: Synthesis of α-(Hetero)aryl C-Glycosides

Anti-inflammatory role of SGLT2 inhibitors as part of their anti-atherosclerotic activity: Data from basic science and clinical trials

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SGLT inhibitors as antidiabetic agents: a comprehensive review

Abstract: Diabetes is one of the most common disorders that substantially contributes to an increase in global health burden.

Cited by 24 publications

References 160 publications

Coronary Microvascular Dysfunction in Diabetes Mellitus: Pathogenetic Mechanisms and Potential Therapeutic Options

Coronary Microvascular Dysfunction in Diabetes Mellitus: Pathogenetic Mechanisms and Potential Therapeutic Options

Diastereoselective Pd-Catalyzed Anomeric C(sp3)–H Activation: Synthesis of α-(Hetero)aryl C-Glycosides

Anti-inflammatory role of SGLT2 inhibitors as part of their anti-atherosclerotic activity: Data from basic science and clinical trials

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Diastereoselective Pd-Catalyzed Anomeric C(sp³)–H Activation: Synthesis of α-(Hetero)aryl C-Glycosides