Chances and risks of SGLT2 inhibitors

Mayer, Péter

doi:10.1007/s00210-011-0720-0

Cited by 6 publications

(5 citation statements)

References 25 publications

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“…Importantly and even though the number of affected individuals is small, humans with mutations in SGLT2 do not show signs of general renal tubular dysfunction or other pathological changes and seem to have normal life expectancy (Santer and Calado 2010; Vallon and Sharma 2010; Wright et al 2011). Therefore, scientists in academia (Vallon and Sharma 2010; Cangoz et al 2013; Tahrani et al 2013; Ferrannini and Solini 2014), industry (Isaji 2011), and regulatory bodies (Mayer 2012) came to the conclusion that inhibition of SGLT2 may represent a pathophysiologically sound concept for the treatment of type 2 diabetes.…”

Section: Introductionmentioning

confidence: 99%

A comprehensive review of the pharmacodynamics of the SGLT2 inhibitor empagliflozin in animals and humans

Michel

Mayoux

Vallon

2015

Naunyn-Schmiedeberg's Arch Pharmacol

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Empagliflozin (formerly known as BI 10773) is a potent, competitive, and selective inhibitor of the sodium glucose transporter SGLT2, which mediates glucose reabsorption in the early proximal tubule and most of the glucose reabsorption by the kidney, overall. Accordingly, empagliflozin treatment increased urinary glucose excretion. This has been observed across multiple species including humans and was reported under euglycemic conditions, in obesity and, most importantly, in type 2 diabetic patients and multiple animal models of type 2 diabetes and of type 1 diabetes. This led to a reduction in blood glucose, smaller blood glucose excursions during oral glucose tolerance tests, and, upon chronic treatment, a reduction in HbA1c in animal models and patients. In rodents, such effects were observed in early and late phases of experimental diabetes and were associated with preservation of pancreatic β-cell function. Combination studies in animals demonstrated that beneficial metabolic effects of empagliflozin may also manifest when added to other types of anti-hyperglycemic treatments including linagliptin and pioglitazone. While some anti-hyperglycemic drugs lead to weight gain, empagliflozin treatment was associated with reduced body weight in normoglycemic obese and non-obese animals despite an increased food intake, largely due to a loss of adipose tissue; on the other hand, empagliflozin preserved body weight in models of type 1 diabetes. Empagliflozin improved endothelial dysfunction in diabetic rats and arterial stiffness, reduced blood pressure in diabetic patients, and attenuated early signs of nephropathy in diabetic animal models. Taken together, the SGLT2 inhibitor empagliflozin improves glucose metabolism by enhancing urinary glucose excretion; upon chronic administration, at least in animal models, the reductions in blood glucose levels are associated with beneficial effects on cardiovascular and renal complications of diabetes.

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Section: Introductionmentioning

confidence: 99%

A comprehensive review of the pharmacodynamics of the SGLT2 inhibitor empagliflozin in animals and humans

Michel

Mayoux

Vallon

2015

Naunyn-Schmiedeberg's Arch Pharmacol

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“…Loss of water also leads to loss of body weight. Body weight reductions were reported in clinical trials with dapagliflozin (74). One prospective side effect of SGLT2 inhibitors which may prevent their use in near future was observed in clinical trials with dapagliflozin.…”

Section: Limitations Of Sglt2 Inhibitorsmentioning

confidence: 99%

Development and Recent Advancement of SGLT2 Inhibitors for the Treatment Regime of T2DM

Pathania¹,

Kashyap²,

Singh³

et al. 2016

J Biomed

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Oral hypoglycemics are involved in the current treatment therapy for type II diabetes mellitus. Continuous research on developing an improved class of oral hypoglycemic led to the development of SGLT2 inhibitors. Their unique mechanism of action made them most sought after the class of oral hypoglycemic. Various clinical studies have disclosed that SGLT2 inhibitors are devoid of many side effects compared to other classes of oral hypoglycemics. Discovery of these inhibitors began with the extensive studies on phlorizin, which provide the basic architecture for all the other glifozins i.e. SGLT2 inhibitors. Many molecules of this class such as dapagliflozin, canagliflozin, empagliflozin have been approved by USFDA for the treatment of type II diabetes mellitus. This work provides all the disclosed details of approved gliflozins and other gliflozins which are in development phase, in the conquest of finding "fool-proof" gliflozin.

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“…51,52 Compound 27 (461 mg, 60% yield, HPLC purity (condition I): 99.4%) was prepared as a white solid from 24 (826 mg, 2.0 mmol) according to the method described for the synthesis of 25. 13 Ethyl 4-Methylbenzenesulfonate (29). To a stirred solution of ethanol (2.30 g, 50 mmol) in THF (11.5 mL) was added precooled (0− 5 °C) aqueous sodium hydroxide (6 g NaOH in 32.6 mL of water).…”

Section: ■ Conclusionmentioning

confidence: 99%

“…Compound 5 was reported to display a favorable absorption, distribution, metabolism, and excretion (ADME) profile in rats and humans and to control the blood glucose level well. 22 However, safety concerns 29 led an advisory committee to vote against the approval of 5 in January 2012, and drug approval in the United States was delayed even though it was approved in Europe in November 2012.…”

Section: ■ Introductionmentioning

confidence: 99%

Design, Synthesis, and Biological Evaluation of Deuterated C-Aryl Glycoside as a Potent and Long-Acting Renal Sodium-Dependent Glucose Cotransporter 2 Inhibitor for the Treatment of Type 2 Diabetes

Lv²,

Roberge³

et al. 2014

J. Med. Chem.

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SGLT2 inhibitors deuterated at sites susceptible to oxidative metabolism were found to have a slightly longer tmax and half-life (t1/2), dose-dependent increase in urinary glucose excretion (UGE) in rats, and slightly superior effects on UGE in dogs while retaining similar in vitro inhibitory activities against hSGLT2. In particular, deuterated compound 41 has the potential to be a robust long-acting antidiabetic agent.

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Chances and risks of SGLT2 inhibitors

Cited by 6 publications

References 25 publications

A comprehensive review of the pharmacodynamics of the SGLT2 inhibitor empagliflozin in animals and humans

A comprehensive review of the pharmacodynamics of the SGLT2 inhibitor empagliflozin in animals and humans

Development and Recent Advancement of SGLT2 Inhibitors for the Treatment Regime of T2DM

Design, Synthesis, and Biological Evaluation of Deuterated C-Aryl Glycoside as a Potent and Long-Acting Renal Sodium-Dependent Glucose Cotransporter 2 Inhibitor for the Treatment of Type 2 Diabetes

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