SGLT-2 inhibitors: pharmacokinetics characteristics and effects on lipids

Filippas-Ntekouan, S.; Tsimihodimos, V.; Filippatos, Theodosios D.; Dimitriou, T.; Elisaf, Moses

doi:10.1080/17425255.2018.1541348

Cited by 39 publications

(43 citation statements)

References 62 publications

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“…Peak plasma concentration is achieved in 1.5–2 hours in adults (Table 1). 5 Food consumption does not significantly affect the efficacy of dapagliflozin 6. Dapagliflozin is mainly protein-bound and has the largest volume of distribution (118 L) between the SGLT2 inhibitors 5.…”

Section: Pharmacologymentioning

confidence: 99%

<p>Differential pharmacology and clinical utility of dapagliflozin in type 2 diabetes</p>

Papakitsou

Vougiouklakis

Elisaf

et al. 2019

CPAA

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Dapagliflozin belongs in the family of sodium-glucose cotransporter 2 (SGLT2) inhibitors and acts by reducing glucose reabsorption in the proximal tubule. The aim of this review is to present the differential pharmacology and clinical utility of dapagliflozin. Dapagliflozin is orally administered, has a long half-life of 12.9 hours and (similar to empagliflozin) is a much weaker SGLT1 inhibitor compared with canagliflozin. Dapagliflozin significantly decreases glycated hemoglobin and fasting glucose levels in patients with type 2 diabetes mellitus (T2DM). The drug improves body weight, blood pressure, uric acid, triglycerides and high-density lipoprotein cholesterol. In the DECLARE-TIMI 58 trial, a large trial of 17,160 T2DM patients with established cardiovascular disease (CVD) or without established CVD but with multiple risk factors, dapagliflozin compared with placebo resulted in a significantly lower rate of the composite outcome of CVD death or hospitalization for heart failure (HHF); this effect was mainly due to a lower rate of HHF in the dapagliflozin group (HR: 0.73; 95%CI: 0.61–0.88), whereas no difference was observed in the rate of CVD death (HR: 0.98; 95%CI: 0.82–1.17). Moreover, dapagliflozin was noninferior to placebo with respect to major adverse CVD events. Dapagliflozin exerts beneficial effects on albuminuria. Additionally, in the DECLARE-TIMI 58 trial it significantly reduced the composite renal endpoint (40% decrease in glomerular filtration rate, end stage renal disease, or renal death) in both patients with established CVD and patients with multiple risk factors (overall HR: 0.53; 95%CI: 0.43–0.66). However dapagliflozin, like the other SGLT2 inhibitors, is associated with an increased risk of genital and urinary tract infections (usually mild mycotic infections) and acute kidney injury in cases of reduced extracellular volume. Dapagliflozin is a useful antidiabetic treatment which also exerts beneficial effects in the management of heart failure and diabetic kidney disease.

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Section: Pharmacologymentioning

confidence: 99%

<p>Differential pharmacology and clinical utility of dapagliflozin in type 2 diabetes</p>

Papakitsou

Vougiouklakis

Elisaf

et al. 2019

CPAA

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“…Except for the quantitative effects of SGLT2i on serum lipids, studies with SGLT2i have shown changes in lipoprotein sub-fractions [94]. A Japanese study reported that Dapa administration suppressed atherogenic small dense LDL-C, whereas it increased HDL2-C, which is a favorable cardiometabolic marker [95].…”

Section: Cardiovascular Effect Of Sglt2imentioning

confidence: 99%

“…To sum up, SGLT2i administration is associated with a small increase in LDL-C and HDL-C levels, while triglyceride and small dense LDL levels tend to modestly decrease [94].…”

Section: Cardiovascular Effect Of Sglt2imentioning

confidence: 99%

SGLT2 Inhibitors: A Review of Their Antidiabetic and Cardioprotective Effects

Tentolouris

Vlachakis

Tzeravini

et al. 2019

IJERPH

196

131

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Type 2 diabetes mellitus is a chronic metabolic disease associated with high cardiovascular (CV) risk. Sodium-glucose co-transporter 2 inhibitors (SGLT2i) are the latest class of antidiabetic medication that inhibit the absorption of glucose from the proximal tubule of the kidney and hence cause glycosuria. Four SGLT2i are currently commercially available in many countries: canagliflozin, dapagliflozin, empagliflozin, and ertugliflozin. SGLT2i reduce glycated hemoglobin by 0.5%–1.0% and have shown favorable effects on body weight, blood pressure, lipid profile, arterial stiffness and endothelial function. More importantly, SGLT2i have demonstrated impressive cardioprotective and renoprotective effects. The main mechanisms underlying their cardioprotective effects have been attributed to improvement in cardiac cell metabolism, improvement in ventricular loading conditions, inhibition of the Na+/H+ exchange in the myocardial cells, alteration in adipokines and cytokines production, as well as reduction of cardiac cells necrosis and cardiac fibrosis. The main adverse events of SGLT2i include urinary tract and genital infections, as well as euglycemic diabetic ketoacidosis. Concerns have also been raised about the association of SGLT2i with lower limb amputations, Fournier gangrene, risk of bone fractures, female breast cancer, male bladder cancer, orthostatic hypotension, and acute kidney injury.

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“…Hal ini dapat diartikan bahwa akan terjadi peningkatan penderita sebanyak 56,2% dari tahun 2015 sampai 2040 (Aziz et al, 2020). Selain itu, individu dengan DM tipe 2 berisiko tinggi mengalami berbagai penyakit penyerta, seperti peningkatan tekanan darah, dislipidemia, dan hiperkoagulabilitas, yang secara substansial meningkatkan risiko kardiovaskular (Filippas-Ntekouan et al, 2018). DM tipe 2 sering dikaitkan dengan komorbiditas yang memperburuk risiko kardiovaskular, seperti obesitas dan hipertensi.…”

Section: Pendahuluanunclassified

“…Sodiumglucose co-transporter-2 (SGLT-2) inhibitor adalah kelas terbaru dari agen hipoglikemik oral yang disetujui. Sebagai kategori baru, karakteristik farmakokinetik obat-obatan ini penting bagi dokter untuk memilih rejimen yangpaling tepat (Filippas-Ntekouan et al, 2018). SGLT-2 inhibitor telah direkomendasikan oleh pedoman klinis sebagai pendekatan farmakologis potensial untuk terapi lini kedua setelah kegagalan metformin atau intoleransi.…”

Section: Pendahuluanunclassified

Effect of SGLT-2 Inhibitor Therapy on Cardiovascular Health in Diabetes Mellitus Patients

Destiana

2019

jppp

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Penyakit kardiovaskular telah menjadi penyebab utama mortalitas dan morbiditas pada pasien dengan diabetes melitus tipe 2. Faktor utama peningkatan risiko penyakit kardiovaskular antara lain hiperglikemia kronis, penurunan sensitivitas insulin, adipositas viseral, dan khususnya komorbiditas hipertensi dan peningkatan arterial stiffness. Sementara itu, sodium-glukosa cotransporter-2 inhibitor, kategori baru dalam terapi diabetes diketahui mengurangi glukosa darah pada pasien dengan meningkatkan glikosuria melalui penghambatan reabsorpsi glukosa urin. Terapi tersebut juga menghasilkan diuresis osmotik yang diinduksi glukosa, penurunan berat badan, dan penurunan tekanan darah. Tujuan dari literature review ini adalah untuk mengetahui efek sodium-glukosa co-transporter-2 inhibitor terhadap kesehatan kardiovaskular pada pasien diabetes mellitus. Penelitian ini merupakan literature review yang melibatkan sumber pustaka sebanyak 20 pustaka yang berasal dari 3 jurnal nasional dan 17 jurnal internasional dengan kata kunci yang digunakan antara lain diabetes mellitus,cardiovascular dan SGLT-2 inhibitor. Beberapa penelitian secara signifikan menunjukkan efek SGLT-2 inhibitor pada kesehatan kardiovaskular, yang terlihat dengan adanya penurunan mortalitas dan rawat inap gagal jantung, tekanan darah dan renal outcome yang lebih baik, peningkatan fungsi jantung pada kardiomiopati diabetes dan iskemik miokard.

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SGLT-2 inhibitors: pharmacokinetics characteristics and effects on lipids

Cited by 39 publications

References 62 publications

<p>Differential pharmacology and clinical utility of dapagliflozin in type 2 diabetes</p>

<p>Differential pharmacology and clinical utility of dapagliflozin in type 2 diabetes</p>

SGLT2 Inhibitors: A Review of Their Antidiabetic and Cardioprotective Effects

Effect of SGLT-2 Inhibitor Therapy on Cardiovascular Health in Diabetes Mellitus Patients

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