Pharmacokinetics of Empagliflozin, a Sodium Glucose Cotransporter-2 (SGLT-2) Inhibitor, Coadministered with Sitagliptin in Healthy Volunteers

Brand, Tobias; Macha, Sreeraj; Mattheus, Michaela; Pinnetti, Sabine; Woerle, Hans J.

doi:10.1007/s12325-012-0055-3

Cited by 56 publications

(35 citation statements)

References 14 publications

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“…Similarly, coadministration of empagliflozin 50 mg with sitagliptin 100 mg did not have a clinically meaningful effect on the AUC tau,ss or C max,ss of sitagliptin (Table 5). These results indicate that empagliflozin and sitagliptin can be co-administered without dose adjustments [67] .…”

Section: Pharmacokineticsmentioning

confidence: 78%

“…An open label, randomised, multiple-dose (5 days), crossover study with three treatments and two treatment sequences investigated the potential DDI between empagliflozin and sitagliptin in 16 healthy male volunteers [67] . Co-administration of sitagliptin 100 mg with empagliflozin 50 mg did not have a clinically relevant effect on the AUC tau,ss or C max,ss of the analyte in plasma at steady state over a uniform dosing interval tau of empagliflozin (Table 5).…”

Section: Pharmacokineticsmentioning

confidence: 99%

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Pharmacokinetic Characteristics and Clinical Efficacy of an SGLT2 Inhibitor Plus DPP-4 Inhibitor Combination Therapy in Type 2 Diabetes

Scheen

2016

Clin Pharmacokinet

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SUMMARYType 2 diabetes (T2D) generally requires a combination of several pharmacological approaches to control hyperglycaemia. Combining a sodium-glucose cotransporter type 2 inhibitor (SGLT2i, known as gliflozin) and a dipeptidyl peptidase-4 inhibitor known as gliptin) appears to be an attractive strategy because of complementary modes of action.This narrative review analyzes the pharmacokinetics and clinical efficacy of different combined therapies with a SGLT2i (canagliflozin, dapagliflozin, empagliflozin, ertugliflozin, ipragliflozin, luseogliflozin, tofogliflozin) and a DPP-4i (linagliptin, saxagliptin, sitagliptin, teneligliptin). Drug-drug pharmacokinetic interaction studies do not show any significant changes in peak concentrations (C max ) and total exposure (area under the curve of plasma concentrations or AUC) of either drug when they were given orally together compared to corresponding values when each of them was absorbed alone. Some fixed-dose combinations (FDC) are already available (dapagliflozin-saxagliptin, empagliflozin-linagliptin) or in development (ertugliflozin-sitagliptin), and preliminary results showed bioequivalence of the two medications given as FDC tablets when compared with co-administration of the individual tablets. Dual therapy is more potent than either monotherapy in patients treated with diet and exercise or already treated with metformin. SGLT2i and DPP-4i could be used as initial combination or in a stepwise approach. The additional glucose-lowering effect appears to be more marked when a gliflozin is added to a gliptin than when a gliptin is added to a gliflozin. Combining the two pharmacological options is safe and does not induce hypoglycaemia. Key-words : Combined therapy -DPP-4 inhibitor -Fixed-dose combination -SGLT2 inhibitor -Type 2 diabetesKey points -The combination of a sodium-glucose cotransporter type 2 inhibitor (SGLT2i), which promotes glycosuria and improves glucose tolerance independently of insulin, and a dipeptidyl peptidase-4 inhibitor (DPP-4i), an incretin-based therapy that corrects islet dysfunction, is an attractive approach for the management of type 2 diabetes.-Both dapagliflozin plus saxagliptin and empagliflozin plus linagliptin combined therapies have been tested as separate tablets (no clinically relevant pharmacokinetic drug-drug interactions) and as fixed-dose combination (FDC: bioequivalence studies); such combined therapies are more efficacious than either monotherapy to control blood glucose, without worsening of the safety profile.-Other combinations of a SGLT2i and a DPP-4i have been evaluated in studies that also showed the absence of drug-drug pharmacokinetic interactions and better glucose control compared to either therapy alone. An ertugliflozin-sitagliptin FDC is in current development.-Initial SGLT2i -DPP-4i combination may be considered or one medication may be added to the other, with apparently better results when the SGLT2i was added to the DPP-4i compared with the reverse sequence. However, which glucose-lowering agent sh...

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Section: Pharmacokineticsmentioning

confidence: 78%

Section: Pharmacokineticsmentioning

confidence: 99%

Pharmacokinetic Characteristics and Clinical Efficacy of an SGLT2 Inhibitor Plus DPP-4 Inhibitor Combination Therapy in Type 2 Diabetes

Scheen

2016

Clin Pharmacokinet

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“…The combination therapy of empagliflozin with other existing anti-diabetic drugs has been effective in reducing the glycaemic levels. [13][14][15][16] Moreover, the combination therapy has demonstrated no harmful drug interactions. Therefore, monotherapy and combination therapy with empagliflozin is a potential new approach for the treatment of T2DM.…”

Section: Efficacy Of Empagliflozin As Monotherapy and Combination Thementioning

confidence: 99%

Empagliflozin: an exciting prospect in the treatment of diabetes

Srinivas¹,

George²,

Sriram³

2017

Int J Basic Clin Pharmacol

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Type 2 diabetes mellitus (T2DM) continues to be a chronic and disabling disease that is associated with high mortality and morbidity. The epidemic burden of diabetes mellitus has increased in developing countries and Asia is considered as the “diabetic epicentre”. Type 2 diabetes (T2DM), is characterised by reduced secretion of insulin from pancreatic beta cells independently or associated with reduced response of peripheral tissues to circulating insulin. A proper glycaemic control is essential to delay the micro and macrovascular complications of T2DM. Standard anti-diabetic agents including insulin happen to induce minor to major adverse outcomes in certain populations over prolonged period of administration. Hence there has been a compelling need to develop newer and novel approach to treatment of T2DM. Sodium-glucose co-transporter 2 (SGLT-2) inhibitors are a novel category of drugs that happen to reduce glycaemic overload by inducing glycosuria. The safety, efficacy and tolerability profile of these drugs were studied separately under various trials and was approved for use in August 2014 by US-FDA. This review is an attempt to describe the history of SGLT-2 inhibitors, their mechanism of action, safety and efficacy as well as its current status among anti-diabetic agents.

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“…It is co-administered with other oral glucose-lowering agents (metformin, sitagliptin, linagliptin and glimepiride) in combination therapy of diabetes management. [16][17][18][19] It is also administered with cardiovascular/ antihypertensive compounds (diuretics, verapamil, ramipril and digoxin) and cholesterol lowering agent (simvastatin) in cases of diabetes with hypertension and diabetes with hyperlipidemia. 21,22 It can be administered with an anticoagulant (warfarin) and an oral contraceptive (ethinylestradiol/ levonorgestrel).…”

Section: Pharmacokineticsmentioning

confidence: 99%

Empagliflozin: a wonder drug in preventing diabetic nephropathy and cardiovascular effects

Naveena

2016

Int J Basic Clin Pharmacol

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Pharmacokinetics of Empagliflozin, a Sodium Glucose Cotransporter-2 (SGLT-2) Inhibitor, Coadministered with Sitagliptin in Healthy Volunteers

Abstract: These results indicate that empagliflozin and sitagliptin can be coadministered without dose adjustments.

Cited by 56 publications

References 14 publications

Pharmacokinetic Characteristics and Clinical Efficacy of an SGLT2 Inhibitor Plus DPP-4 Inhibitor Combination Therapy in Type 2 Diabetes

Pharmacokinetic Characteristics and Clinical Efficacy of an SGLT2 Inhibitor Plus DPP-4 Inhibitor Combination Therapy in Type 2 Diabetes

Empagliflozin: an exciting prospect in the treatment of diabetes

Empagliflozin: a wonder drug in preventing diabetic nephropathy and cardiovascular effects

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