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Pharmacokinetic and pharmacodynamic profile of empagliflozin, a sodium glucose co-transporter 2 inhibitor.

Scheen AJ - Clin Pharmacokinet (2014)

Bottom Line: SGLT2 inhibitors exert their effects independently of insulin.Clinical studies did not reveal any relevant drug-drug interactions with several other drugs commonly prescribed to patients with T2DM, including warfarin.Increased UGE resulted in proportional reductions in fasting plasma glucose and mean daily glucose concentrations.

View Article: PubMed Central - PubMed

Affiliation: Division of Diabetes, Nutrition and Metabolic Disorders and Division of Clinical Pharmacology, Department of Medicine, CHU Sart Tilman (B35), University of Liège, B-4000, Liège 1, Belgium, andre.scheen@chu.ulg.ac.be.

ABSTRACT
Empagliflozin is an orally active, potent and selective inhibitor of sodium glucose co-transporter 2 (SGLT2), currently in clinical development to improve glycaemic control in adults with type 2 diabetes mellitus (T2DM). SGLT2 inhibitors, including empagliflozin, are the first pharmacological class of antidiabetes agents to target the kidney in order to remove excess glucose from the body and, thus, offer new options for T2DM management. SGLT2 inhibitors exert their effects independently of insulin. Following single and multiple oral doses (0.5-800 mg), empagliflozin was rapidly absorbed and reached peak plasma concentrations after approximately 1.33-3.0 h, before showing a biphasic decline. The mean terminal half-life ranged from 5.6 to 13.1 h in single rising-dose studies, and from 10.3 to 18.8 h in multiple-dose studies. Following multiple oral doses, increases in exposure were dose-proportional and trough concentrations remained constant after day 6, indicating a steady state had been reached. Oral clearance at steady state was similar to corresponding single-dose values, suggesting linear pharmacokinetics with respect to time. No clinically relevant alterations in pharmacokinetics were observed in mild to severe hepatic impairment, or in mild to severe renal impairment and end-stage renal disease. Clinical studies did not reveal any relevant drug-drug interactions with several other drugs commonly prescribed to patients with T2DM, including warfarin. Urinary glucose excretion (UGE) rates were higher with empagliflozin versus placebo and increased with dose, but no relevant impact on 24-h urine volume was observed. Increased UGE resulted in proportional reductions in fasting plasma glucose and mean daily glucose concentrations.

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Related in: MedlinePlus

Structural formula of empagliflozin
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Fig1: Structural formula of empagliflozin

Mentions: The subject of this review is empagliflozin (BI 10773; 1-chloro-4-(β-d-glucopyranos-1-yl)-2-[4-((S)-tetrahydrofuran-3-yl-oxy)-benzyl]-benzene; C23H27ClO7; molecular weight 450.9; Fig. 1), an orally active, potent and selective inhibitor of SGLT2 being studied for the treatment of patients with T2DM [8, 12], developed by Boehringer Ingelheim and Eli Lilly and Company. Phase III trials of empagliflozin given as monotherapy or in combination with oral antidiabetes drugs or insulin reported statistically significant and clinically relevant improvements in glycaemic control, body weight and systolic blood pressure when compared with placebo and active comparators [13–17]. Adverse events with SGLT2 inhibitors include increased rates of genital infection and urinary tract infection, which are attributed to elevated urinary glucose levels. More patients on empagliflozin than on placebo reported events consistent with genital infection; however, events consistent with urinary tract infection were comparable in both groups [18]. Empagliflozin is currently progressing through phase III clinical trials, while regulatory decisions are awaited for marketing applications recently submitted in the USA and Europe.Fig. 1


Pharmacokinetic and pharmacodynamic profile of empagliflozin, a sodium glucose co-transporter 2 inhibitor.

Scheen AJ - Clin Pharmacokinet (2014)

Structural formula of empagliflozin
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3927118&req=5

Fig1: Structural formula of empagliflozin
Mentions: The subject of this review is empagliflozin (BI 10773; 1-chloro-4-(β-d-glucopyranos-1-yl)-2-[4-((S)-tetrahydrofuran-3-yl-oxy)-benzyl]-benzene; C23H27ClO7; molecular weight 450.9; Fig. 1), an orally active, potent and selective inhibitor of SGLT2 being studied for the treatment of patients with T2DM [8, 12], developed by Boehringer Ingelheim and Eli Lilly and Company. Phase III trials of empagliflozin given as monotherapy or in combination with oral antidiabetes drugs or insulin reported statistically significant and clinically relevant improvements in glycaemic control, body weight and systolic blood pressure when compared with placebo and active comparators [13–17]. Adverse events with SGLT2 inhibitors include increased rates of genital infection and urinary tract infection, which are attributed to elevated urinary glucose levels. More patients on empagliflozin than on placebo reported events consistent with genital infection; however, events consistent with urinary tract infection were comparable in both groups [18]. Empagliflozin is currently progressing through phase III clinical trials, while regulatory decisions are awaited for marketing applications recently submitted in the USA and Europe.Fig. 1

Bottom Line: SGLT2 inhibitors exert their effects independently of insulin.Clinical studies did not reveal any relevant drug-drug interactions with several other drugs commonly prescribed to patients with T2DM, including warfarin.Increased UGE resulted in proportional reductions in fasting plasma glucose and mean daily glucose concentrations.

View Article: PubMed Central - PubMed

Affiliation: Division of Diabetes, Nutrition and Metabolic Disorders and Division of Clinical Pharmacology, Department of Medicine, CHU Sart Tilman (B35), University of Liège, B-4000, Liège 1, Belgium, andre.scheen@chu.ulg.ac.be.

ABSTRACT
Empagliflozin is an orally active, potent and selective inhibitor of sodium glucose co-transporter 2 (SGLT2), currently in clinical development to improve glycaemic control in adults with type 2 diabetes mellitus (T2DM). SGLT2 inhibitors, including empagliflozin, are the first pharmacological class of antidiabetes agents to target the kidney in order to remove excess glucose from the body and, thus, offer new options for T2DM management. SGLT2 inhibitors exert their effects independently of insulin. Following single and multiple oral doses (0.5-800 mg), empagliflozin was rapidly absorbed and reached peak plasma concentrations after approximately 1.33-3.0 h, before showing a biphasic decline. The mean terminal half-life ranged from 5.6 to 13.1 h in single rising-dose studies, and from 10.3 to 18.8 h in multiple-dose studies. Following multiple oral doses, increases in exposure were dose-proportional and trough concentrations remained constant after day 6, indicating a steady state had been reached. Oral clearance at steady state was similar to corresponding single-dose values, suggesting linear pharmacokinetics with respect to time. No clinically relevant alterations in pharmacokinetics were observed in mild to severe hepatic impairment, or in mild to severe renal impairment and end-stage renal disease. Clinical studies did not reveal any relevant drug-drug interactions with several other drugs commonly prescribed to patients with T2DM, including warfarin. Urinary glucose excretion (UGE) rates were higher with empagliflozin versus placebo and increased with dose, but no relevant impact on 24-h urine volume was observed. Increased UGE resulted in proportional reductions in fasting plasma glucose and mean daily glucose concentrations.

Show MeSH
Related in: MedlinePlus