Pharmacotherapy of type 2 diabetes: An update

Upadhyay, Jagriti; Polyzos, Stergios A.; Perakakis, Nikolaos; Thakkar, Bindiya; Paschou, Stavroula Α.; Katsiki, Niki; Underwood, Patricia; Park, Kyung-Hee; Seufert, Jochen; Kang, Eun Seok; Sternthal, Elliot; Karagiannis, Asterios; Mantzoros, Christos S.

doi:10.1016/j.metabol.2017.08.010

Cited by 169 publications

(105 citation statements)

References 346 publications

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“…SGLT2 inhibitors represent a new antidiabetic drug category that reduce renal tubular absorption of glucose, thus enhancing glycosuria and resulting in blood glucose lowering and improved glycemic control (Vallon, 2015). Apart from glucose reduction, SGLT2 inhibitors may beneficially affect several cardiometabolic risk factors, such as body weight, blood pressure, uric acid, fat distribution, arterial stiffness, and vascular resistance, as well as cardiac metabolism, function, and hemodynamics (Athyros, Katsiki, & Karagiannis, 2016;Kaplan et al, 2018;Katsiki, Athyros, & Mikhailidis, 2017;Katsiki, Mikhailidis, & Theodorakis, 2017;Katsiki, Purrello, Tsioufis, & Mikhailidis, 2017;Mamakou et al, 2017;Tikkanen, Chilton, & Johansen, 2016;Upadhyay et al, 2018;).…”

Section: Sglt2 Inhibitorsmentioning

confidence: 99%

Sodium–glucose cotransporter 2 inhibitors and inflammation in chronic kidney disease: Possible molecular pathways

Yaribeygi

Butler

Atkin

et al. 2018

Journal Cellular Physiology

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117

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Clinical trials with sodium-glucose cotransporter 2 (SGLT2) inhibitors (empagliflozin, dapagliflozin, and canagliflozin) have shown a decrease in the progression of chronic kidney disease (CKD). SGLT2 inhibitors represent a new category of oral antidiabetic agents that can also reduce systolic and diastolic blood pressure, as well as serum uric acid, and improve the glomerular filtration rate. Apart from affecting renal hemodynamics and glycotoxicity, evidence suggests that SGLT2 inhibitors may be renoprotective due to their effects on inflammation in renal tissues. Inflammatory responses play a prominent role in the pathophysiology of CKD as several structural and functional disorders of renal failure are strongly related to the overproduction of proinflammatory mediators. The present review discusses the anti-inflammatory properties of SGLT2 inhibitors. The different molecular pathways through which SGLT2 inhibitors may affect inflammation in the kidneys are also commented upon.

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Section: Sglt2 Inhibitorsmentioning

confidence: 99%

Sodium–glucose cotransporter 2 inhibitors and inflammation in chronic kidney disease: Possible molecular pathways

Yaribeygi

Butler

Atkin

et al. 2018

Journal Cellular Physiology

Self Cite

117

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“…Type 2 diabetes (T2D) is a chronic disease with quickly rising prevalence worldwide and estimated to affect 642 million individuals by 2040 . It is a major cause of death and imposes a significant burden on the healthcare economy . Treatment of T2D includes diet, physical exercise and pharmacotherapy .…”

Section: Introductionmentioning

confidence: 99%

“…Recent studies indicate that high‐intensity interval exercise (HIIE) is one of the most suitable exercise types for T2D treatment . As for pharmacotherapy, metformin is considered the first‐line agent in the management of T2D . Metformin is a strong base, present as a hydrophilic cation in biological fluids .…”

Section: Introductionmentioning

confidence: 99%

“…1 It is a major cause of death and imposes a significant burden on the healthcare economy. 2 Treatment of T2D includes diet, physical exercise and pharmacotherapy. 3 Recent studies indicate that high-intensity interval exercise (HIIE) is one of the most suitable exercise types for T2D treatment.…”

Section: Introductionmentioning

confidence: 99%

“…4,5 As for pharmacotherapy, metformin is considered the first-line agent in the management of T2D. 2 Metformin is a strong base, present as a hydrophilic cation in biological fluids. 6 It is not metabolized Exercise is widely accepted as having therapeutic effects; thus, it is important to know whether it interacts with medications.…”

Section: Introductionmentioning

confidence: 99%

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Effect of exercise on key pharmacokinetic parameters related to metformin absorption in healthy humans: A pilot study

Nikolaidis

Virgiliou

Vekiou³

et al. 2020

Scandinavian Med Sci Sports

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Exercise is widely accepted as having therapeutic effects; thus, it is important to know whether it interacts with medications. The aim of the present pilot study was to examine the effect of high‐intensity interval exercise (known to have antidiabetic action) on key pharmacokinetic parameters related to absorption of metformin (the first‐line medication against type 2 diabetes). Ten healthy men participated in two sessions, spaced one to two weeks apart in random, counterbalanced order. In both sessions, participants received 1000 mg of metformin orally, 1‐1.5 hours after breakfast. Then, they either ran for 60 minutes at alternating intensity, starting at 40 minutes after metformin administration, and rested without food consumption over the next 3 hours or they rested without food consumption during the entire testing period. Venous blood samples were collected before and at 0.5, 2, 2.5, 3, 3.5, 4, and 4.5 hours after metformin administration for metformin determination by liquid chromatography‐mass spectrometry. Capillary blood samples were also collected for lactate and glucose measurements. Data from the two sessions were compared through Wilcoxon or Student's t test, as appropriate. Maximum plasma concentration of metformin (Cmax) was higher at exercise compared to rest (P = .059). Time to reach Cmax (Tmax) decreased with exercise (P = .009), and the area under the metformin concentration vs time curve was higher at exercise (P = .047). The addition of exercise to metformin administration did not cause hypoglycemia or lactic acidosis. In conclusion, our results provide the first evidence that pharmacokinetic values related to metformin absorption are affected by exercise.

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Glucagon‐Like Peptide‐1 Receptor Activators

Wagner¹,

Evers²,

Bossart³

et al. 2021

Burger's Medicinal Chemistry and Drug Discovery

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Type 2 diabetes (T2D) and obesity have reached pandemic levels and represent a major health burden to modern society. Peptidic GLP‐1 receptor agonists (GLP‐1RAs) have been established as an effective therapy with respect to glycemic control and provide moderate body weight reduction. Marketed first‐generation GLP‐1RAs are suitable for once‐ or twice‐daily subcutaneous dosing. Their substantial benefit on glucose control led to the discovery and development of longer lasting therapeutic options to improve patient convenience and compliance. Recently reported positive cardiovascular outcome studies for some GLP‐1RAs further underscore their therapeutic value. Besides long‐lasting action, alternative delivery formats for injectable GLP‐1RAs have been explored, for example oral formulations. One such oral formulation of a GLP‐1 analog has completed Phase 3 studies and is now approved for the treatment of T2D. In contrast, the discovery of orally available small molecule agonists of the GLP‐1R has been historically challenging, and only recently a few compounds have reached early clinical development. To further improve the efficacy of GLP‐1RAs, so‐called GLP‐1R dual or triple agonists have been developed. These peptides show promising results in early clinical trials but are awaiting confirmation of their therapeutic benefit in late‐stage development.

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Pharmacotherapy of type 2 diabetes: An update

Cited by 169 publications

References 346 publications

Sodium–glucose cotransporter 2 inhibitors and inflammation in chronic kidney disease: Possible molecular pathways

Sodium–glucose cotransporter 2 inhibitors and inflammation in chronic kidney disease: Possible molecular pathways

Effect of exercise on key pharmacokinetic parameters related to metformin absorption in healthy humans: A pilot study

Glucagon‐Like Peptide‐1 Receptor Activators

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