Empagliflozin

Empagliflozin

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  Dr Shinde VirajAshok Junior resident 2 Department of Pharmacology GMC Nagpur
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   Introduction Pharmacodynamics Pharmacokinetics Adverse drug reaction Currentstatus Overview
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    Belongs tosodium glucose co- transporter inhibitor group  Other drugs belonging to this group are dapagliflozin, sergliflozin , remogliflozin, canagliflozin Introduction
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   Potent highly selectiveSodium Glucose Cotransporter 2 inhibitor
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   Drug  Inhibits reabsorptionof filtered glucose in proximal tubule and  Lowers renal threshold for glucose - ↑ urinary glucose excretion  ↓ blood glucose levels  Dose dependent ↑ glycosuria with doses ≤ 1oomg Pharmacodynamics
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    In astudy, empagliflozin resulted in 1. Improvements in β cell function and insulin sensitivity 2. ↓ insulin secretion and tissue glucose disposal  No clinically relevant effects of single doses of empagliflozin 25mg and 200mg on heart rate corrected QT interval
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    No clinicallyrelevant effects of food  Vd - 73.8 L  Steady state – 5 – 6 days Pharmacokinetics
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    37 %in RBC & 86 % plasma protein bound  Primary route of metabolism – hepatic glucuronidation (UGT)  Excretion  41% eliminated in faeces- majority as unchanged  54% eliminated in urine – of which 50% was unchanged Contd …
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    Avoid coadministrationwith drugs known to induce UGT(5’ uridine diphosphoglucuronyltransferase) enzymes ( phenytoin & carbamazepine)  Doesn’t inhibit , inactivate or induce cytochrome P450 enzymes Drug interactions Potential risk of ↓ efficacy
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    Starting dose– 10mg once daily as  Monotherapy or  In combination with other antihyperglycaemic agents  Patients tolerating this dose & who require tighter glycaemic control  Dosage – may be ↑ to 25 mg ( maximum dose) Dosage & administration
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    Common –1- 10% of patients  Genital infections  Urinary tract infections  Pruritus  ↑ urination Adverse reactions
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    May addto diuretic effects of thiazide & loop diuretics - ↑ risk of dehydration & hypotension  Frequency of minor or major hypoglycaemia was similar to placebo recipient  Risk of hypoglycaemia increases when coadministered with a sulfonylurea and /or insulin
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    Approved inEU and USA and based on most recent guidelines (2013)  First line monotherapy (though not typically first choice) or  Add on therapy to other antihyperglycaemic agents (dual or triple combination)  SGLT 2 inhibitors - associated with body weight loss (may be used in obese patients) Current status of Empagliflozin
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   Add ontherapy to metformin  Non inferior to glimepiride at 52 weeks  Superior to glimepiride at 104 weeks in terms of reduction of HbA1C  In clinical trials overall number of empagliflozin treated patients who developed kidney and bladder cancer was low and similar to that in placebo recipients
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    Empagliflozin :A review of its use in patients with Type 2 Diabetes Mellitus ; Drugs (2014)74 , Lesley J Scott  The sodium glucose cotransporter 2 inhibitor empagliflozin does not prolong QT interval in a thorough QT (TQT) study, Ring et al. Cardiovascular Diabetology 2013, - bio med central References
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