Drug-Drug Interactions with Sodium-Glucose Cotransporters Type 2 (SGLT2) Inhibitors, New Oral Glucose-Lowering Agents for the Management of Type 2 Diabetes Mellitus.
[en] Inhibitors of sodium-glucose cotransporters type 2 (SGLT2) reduce hyperglycaemia by decreasing renal glucose threshold and thereby increasing urinary glucose excretion. They are proposed as a novel approach for the management of type 2 diabetes mellitus. They have proven their efficacy in reducing glycated haemoglobin, without inducing hypoglycaemia, as monotherapy or in combination with various other glucose-lowering agents, with the add-on value of promoting some weight loss and lowering arterial blood pressure. As they may be used concomitantly with many other drugs, we review the potential drug-drug interactions (DDIs) regarding the three leaders in the class (dapagliglozin, canagliflozin and empagliflozin). Most of the available studies were performed in healthy volunteers and have assessed the pharmacokinetic interferences with a single administration of the SGLT2 inhibitor. The exposure [assessed by peak plasma concentrations (C max) and area under the concentration-time curve (AUC)] to each SGLT2 inhibitor tested was not significantly influenced by the concomitant administration of other glucose-lowering agents or cardiovascular agents commonly used in patients with type 2 diabetes. Reciprocally, these medications did not influence the pharmacokinetic parameters of dapagliflozin, canagliflozin or empagliflozin. Some modest changes were not considered as clinically relevant. However, drugs that could specifically interfere with the metabolic pathways of SGLT2 inhibitors [rifampicin, inhibitors or inducers of uridine diphosphate-glucuronosyltransferase (UGT)] may result in significant changes in the exposure of SGLT2 inhibitors, as shown for dapagliflozin and canagliflozin. Potential DDIs in patients with type 2 diabetes receiving chronic treatment with an SGLT2 inhibitor deserve further attention, especially in individuals treated with several medications or in more fragile patients with hepatic and/or renal impairment.
Scheen, André ; Université de Liège - ULiège > Département des sciences cliniques > Diabétologie, nutrition et maladie métaboliques
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Anglais
Titre :
Drug-Drug Interactions with Sodium-Glucose Cotransporters Type 2 (SGLT2) Inhibitors, New Oral Glucose-Lowering Agents for the Management of Type 2 Diabetes Mellitus.
Scheen AJ, Lefebvre PJ. Oral antidiabetic agents: a guide to selection. Drugs. 1998;55(2):225-36.
Krentz AJ, Bailey CJ. Oral antidiabetic agents: current role in type 2 diabetes mellitus. Drugs. 2005;65(3):385-411.
Scheen AJ, Lefèbvre PJ. Antihyperglycemic agents: drug interactions of clinical importance. Drug Saf. 1995;12(1):32-45.
Scheen AJ, Demagalhaes A, Salvatore T, et al. Reduction of the acute bioavailability of metformin by the alpha-glucosidase inhibitor acarbose in normal man. Eur J Clin Investig. 1994;24:50-4.
Inzucchi SE, Bergenstal RM, Buse JB, et al. Management of hyperglycaemia in type 2 diabetes: a patient-centered approach. Position statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetologia. 2012;55(6):1577-96.
Bennett WL, Maruthur NM, Singh S, et al. Comparative effectiveness and safety of medications for type 2 diabetes: an update including new drugs and 2-drug combinations. Ann Intern Med. 2011;154(9):602-13.
Ryden L, Grant PJ, Anker SD, et al. ESC Guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD: The Task Force on diabetes, pre-diabetes, and cardiovascular diseases of the European Society of Cardiology (ESC) and developed in collaboration with the European Association for the Study of Diabetes (EASD). Eur Heart J. 2013;34(39):3035-87.
Lafeber M, Grobbee DE, Spiering W, et al. The combined use of aspirin, a statin, and blood pressure-lowering agents (polypill components) in clinical practice in patients with vascular diseases or type 2 diabetes mellitus. Eur J Prev Cardiol. 2013;20(5):771-8.
Scheen AJ. Drug interactions of clinical importance with antihyperglycaemic agents: an update. Drug Saf. 2005;28(7):601-31.
Tirkkonen T, Heikkila P, Huupponen R, et al. Potential CYP2C9-mediated drug-drug interactions in hospitalized type 2 diabetes mellitus patients treated with the sulphonylureas glibenclamide, glimepiride or glipizide. J Intern Med. 2010;268(4):359-66.
Scheen AJ. Pharmacokinetic interactions with thiazolidinediones. Clin Pharmacokinet. 2007;46(1):1-12.
Scheen AJ. Drug-drug and food-drug pharmacokinetic interactions with new insulinotropic agents repaglinide and nateglinide. Clin Pharmacokinet. 2007;46(2):93-108.
Scheen AJ. Dipeptidylpeptidase-4 inhibitors (gliptins): focus on drug-drug interactions. Clin Pharmacokinet. 2010;49(9):573-88.
Hurren KM, Pinelli NR. Drug-drug interactions with glucagon-like peptide-1 receptor agonists. Ann Pharmacother. 2012;46(5):710-7.
Tahrani AA, Bailey CJ, Del Prato S, et al. Management of type 2 diabetes: new and future developments in treatment. Lancet. 2011;378(9786):182-97.
Abdul-Ghani MA, Norton L, Defronzo RA. Role of sodium-glucose cotransporter 2 (SGLT 2) inhibitors in the treatment of type 2 diabetes. Endocr Rev. 2011;32(4):515-31.
Vasilakou D, Karagiannis T, Athanasiadou E, et al. Sodium-glucose cotransporter 2 inhibitors for type 2 diabetes: a systematic review and meta-analysis. Ann Intern Med. 2013;159(4):262-74.
Scheen AJ. Evaluating SGLT2 inhibitors for type 2 diabetes: pharmacokinetic and toxicological considerations. Expert Opin Drug Metab Toxicol. doi: 10.1517/17425255.2014.873788.
Plosker GL. Dapagliflozin: a review of its use in type 2 diabetes mellitus. Drugs. 2012;72(17):2289-312.
Kasichayanula S, Liu X, Lacreta F, et al. Clinical pharmacokinetics and pharmacodynamics of dapagliflozin, a selective inhibitor of sodium-glucose co-transporter type 2. Clin Pharmacokinet. 2014;53(1):17-27.
Elkinson S, Scott LJ. Canagliflozin: first global approval. Drugs. 2013;73(9):979-88.
Lamos EM, Younk LM, Davis SN. Canagliflozin, an inhibitor of sodium-glucose cotransporter 2, for the treatment of type 2 diabetes mellitus. Expert Opin Drug Metab Toxicol. 2013;9(6):763-75.
Scheen AJ. Pharmacokinetic and pharmacodynamic profile of empagliflozin, a sodium glucose co-transporter 2 inhibitor. Clin Pharmacokinet. doi: 10.1007/s40262-013-0126-x.
Scheen AJ. Pharmacokinetic considerations for the treatment of diabetes in patients with chronic kidney disease. Expert Opin Drug Metab Toxicol. 2013;9(5):529-50.
Seman L, Macha S, Nehmiz G, et al. Empagliflozin (BI 10773), a potent and selective SGLT2 inhibitor, induces dose-dependent glucosuria in healthy subjects. Clin Pharmacol Drug Dev. 2013;2(2):152-61.
Grempler R, Thomas L, Eckhardt M, et al. Empagliflozin, a novel selective sodium glucose cotransporter-2 (SGLT-2) inhibitor: characterisation and comparison with other SGLT-2 inhibitors. Diabetes Obes Metab. 2012;14(1):83-90.
Kasichayanula S, Liu X, Shyu WC, et al. Lack of pharmacokinetic interaction between dapagliflozin, a novel sodium-glucose transporter 2 inhibitor, and metformin, pioglitazone, glimepiride or sitagliptin in healthy subjects. Diabetes Obes Metab. 2011;13(1):47-54.
Strojek K, Yoon KH, Hruba V, et al. Effect of dapagliflozin in patients with type 2 diabetes who have inadequate glycaemic control with glimepiride: a randomized, 24-week, double-blind, placebo-controlled trial. Diabetes Obes Metab. 2011;13(10):928-38.
Imamura A, Kusunoki M, Ueda S, et al. Impact of voglibose on the pharmacokinetics of dapagliflozin in Japanese patients with type 2 diabetes. Diabetes Ther. 2013;4(1):41-9.
Janssen Pharmaceuticals Inc. Invokana™ (canagliflozin) tablets, for oral use: US prescribing information. 2013. http://www.janssenmd.com/pdf/ invokana/PI-INVOKANA.pdf. Accessed 11 Oct 2013.
Devineni D, Sarich TC, Wexler D, et al. Effects of canagliflozin on the pharmacokinetics (PK) and pharmacodynamics (PD) of metformin and glyburide [abstract no. 2268-PO 2011]. Presented at the American Diabetes Association (ADA) 71st Scientific Sessions; San Diego, CA; 24-28 June 2011.
Macha S, Dieterich S, Mattheus M, et al. Pharmacokinetics of empagliflozin, a sodium glucose cotransporter-2 (SGLT2) inhibitor, and metformin following co-administration in healthy volunteers. Int J Clin Pharmacol Ther. 2013;51(2):132-40.
Macha S, Mattheus M, Pinnetti S, et al. Pharmacokinetics of empagliflozin, a sodium glucose cotransporter 2 inhibitor, and glimepiride following co-administration in healthy volunteers: a randomised, open-label, crossover study. Diab Res Clin Metab. 2012;1:1-7.
Brand T, Macha S, Mattheus M, et al. Pharmacokinetics of empagliflozin, a sodium glucose cotransporter-2 (SGLT-2) inhibitor, coadministered with sitagliptin in healthy volunteers. Adv Ther. 2012;29(10):889-99.
Friedrich C, Metzmann K, Rose P, et al. A randomized, open-label, crossover study to evaluate the pharmacokinetics of empagliflozin and linagliptin after coadministration in healthy male volunteers. Clin Ther. 2013;35(1):A33-42.
Scheen AJ. Cytochrome P450-mediated cardiovascular drug interactions. Expert Opin Drug Metab Toxicol. 2011;7(9):1065-82.
Kasichayanula S, Chang M, Liu X, et al. Lack of pharmacokinetic interactions between dapagliflozin and simvastatin, valsartan, warfarin, or digoxin. Adv Ther. 2012;29(2):163-77.
Devineni D, et al. Lack of clinically meaningful interaction between canagliflozin, a sodium glucose co-transporter 2 inhibitor, and digoxin or warfarin in healthy subjects [poster]. Presented at the 2012 Annual Meeting of the American College of Clinical Pharmacology (ACCP), San Diego, CA: 23-25 September 2012.
Macha S, Rose P, Mattheus M, et al. Lack of drug-drug interaction between empagliflozin, a sodium glucose cotransporter 2 inhibitor, and warfarin in healthy volunteers. Diabetes Obes Metab. 2013;24(15):316-23.
Macha S, Lang B, Pinnetti S, et al. Lack of pharmacokinetic interaction between the sodium glucose cotransporter-2 (SGLT-2) inhibitor empagliflozin and simvastatin in healthy volunteers [abstract no. PCS-33-7]. J Diabetes Investig 2012; 3 Suppl 1: 228.
Macha S, Sennewald R, Rose P, et al. Lack of clinically relevant drug-drug interaction between empagliflozin, a sodium glucose cotransporter 2 inhibitor, and verapamil, ramipril, or digoxin in healthy volunteers. Clin Ther. 2013;35(3):226-35.
Giessmann T, Heise T, Macha S, et al. Lack of interaction between the sodium glucose cotransporter-2 inhibitor empagliflozin and hydrochlorothiazide or torasemide in patients with T2DM [abstract no. 2440-PO]. Diabetes 2012;61 Suppl:A614.
Kasichayanula S, Liu X, Griffen SC, et al. Effects of rifampin and mefenamic acid on the pharmacokinetics and pharmacodynamics of dapagliflozin. Diabetes Obes Metab. 2013;15(3):280-3.
Skee D, Shalayda K, Vandebosch A, et al. The effects of multiple doses of canagliflozin on the pharmacokinetics and safety of single doses of an oral contraceptive containing ethinyl estradiol and levonorgestrel [poster]. Presented at the 111th Annual Meeting of the American Society for Clinical Pharmacology and Therapeutics (ASCPT), Atlanta, GA; 17-20 March 2010.
Devineni D, Curtin CR, Polidori D, et al. Pharmacokinetics and pharmacodynamics of canagliflozin, a sodium glucose co-transporter 2 inhibitor, in subjects with type 2 diabetes mellitus. J Clin Pharmacol. 2013;53(6):601-10.
Macha S, Mattheus M, Pinnetti S, et al. Effect of empagliflozin on the steady-state pharmacokinetics of ethinylestradiol and levonorgestrel in healthy female volunteers. Clin Drug Investig. 2013;20(33):351-7.
Kasichayanula S, Liu X, Pe Benito M, et al. The influence of kidney function on dapagliflozin exposure, metabolism and pharmacodynamics in healthy subjects and in patients with type 2 diabetes mellitus. Br J Clin Pharmacol 2013;76(3):432-44.
Macha S, Mattheus M, Halabi A, et al. Pharmacokinetics, pharmacodynamics and safety of empagliflozin, a sodium glucose cotransporter 2 (SGLT2) inhibitor, in subjects with renal impairment. Diabetes Obes Metab (Epub 16 Jul 2013).
Devineni D, Marbury T, Curtin C, et al. Effects of renal function on canagliflozin (CANA) pharmacokinetics (PK) and pharmacodynamics (PD) in non-diabetic subjects [abstract no. PUB295]. JASN Abstract Supplement of the American Society of Nephrology (ASN) Kidney Week, San Diego California; 30 October-4 November 2012.
Food and Drug Administration. Center for Drug Evaluation and Research report. Canagliflozin (Invokana). http://www.accessdata.fda.gov/drugsatfda-docs/ nda/2013/204042Orig1s000ClinPharmR.pdf. Accessed 09 Jan 2014.
Yale JF, Bakris G, Cariou B, et al. Efficacy and safety of canagliflozin in subjects with type 2 diabetes and chronic kidney disease. Diabetes Obes Metab. 2013;15(5):463-73.
