Abstract
Because management of type 2 diabetes mellitus usually involves combined pharmacological therapy to obtain adequate glucose control and treatment of concurrent pathologies (especially dyslipidaemia and arterial hypertension), drugdrug interactions must be carefully considered with antihyperglycaemic drugs. Additive glucose-lowering effects have been extensively reported when combining sulphonylureas (or the new insulin secretagogues, meglitinide derivatives, i.e. nateglinide and repaglinide) with metformin, sulphonylureas (or meglitinide derivatives) with thiazolidinediones (also called glitazones) and the biguanide compound metformin with thiazolidinediones. Interest in combining α-glucosidase inhibitors with either sulphonylureas (or meglitinide derivatives), metformin or thiazolidinediones has also been demonstrated. These combinations result in lower glycosylated haemoglobin (HbA1c), fasting glucose and postprandial glucose levels than with either monotherapy. Even if modest pharmacokinetic interferences have been reported with some combinations, they do not appear to have important clinical consequences. No significant adverse effects, except a higher risk of hypoglycaemic episodes that may be attributed to better glycaemic control, occur with any combination. Challenging the classical dual therapy with sulphonylurea plus metformin, there is a recent trend to use alternative dual combinations (sulphonylurea plus thiazolidinedione or metformin plus thiazolidinedione). In addition, triple therapy with the addition of a thiazolidinedione to the metformin-sulphonylurea combination has been recently evaluated and allows glucose targets to be reached before insulin therapy is considered. This triple therapy appears to be safe, with no deleterious drug-drug interactions being reported so far.
Potential interferences may also occur between glucose-lowering agents and other drugs, and such drug-drug interactions may have important clinical implications. Relevant pharmacological agents are those that are widely coadministered in diabetic patients (e.g. lipid-lowering agents, antihypertensive agents); those that have a narrow efficacy/toxicity ratio (e.g. digoxin, warfarin); or those that are known to induce (rifampicin [rifampin]) or inhibit (fluconazole) the cytochrome P450 (CYP) system. Metformin is currently a key compound in the pharmacological management of type 2 diabetes, used either alone or in combination with other antihyperglycaemics. There are no clinically relevant metabolic interactions with metformin, because this compound is not metabolised and does not inhibit the metabolism of other drugs. In contrast, sulphonylureas, meglitinide derivatives and thiazolidinediones are extensively metabolised in the liver via the CYP system and thus, may be subject to drug-drug metabolic interactions. Many HMGCoA reductase inhibitors (statins) are also metabolised via the CYP system. Even if modest pharmacokinetic interactions may occur, it is not clear whether drugdrug interactions between oral antihyperglycaemic agents and statins may have clinical consequences regarding both efficacy and safety. In contrast, a marked pharmacokinetic interference has been reported between gemfibrozil and repaglinide and, to a lesser extent, between gemfibrozil and rosiglitazone. This leads to a drastic increase in plasma concentrations of each antihyperglycaemic agent when they are coadministered with the fibric acid derivative, and an increased risk of adverse effects.
Some antihypertensive agents may favour hypoglycaemic episodes when coprescribed with sulphonylureas or meglitinide derivatives, especially ACE inhibitors, but this effect seems to result from a pharmacodynamic drug-drug interaction rather than from a pharmacokinetic drug-drug interaction. No, or only modest, interferences have been described with glucose-lowering agents and other pharmacological compounds such as digoxin or warfarin. The effects of inducers or inhibitors of CYP isoenzymes on the metabolism and pharmacokinetics of the glucose-lowering agents of each pharmacological class has been tested. Significantly increased (with CYP inhibitors) or decreased (with CYP inducers) plasma levels of sulphonylureas, meglitinide derivatives and thiazolidinediones have been reported in healthy volunteers, and these pharmacokinetic changes may lead to enhanced or reduced glucose-lowering action, and thus hypoglycaemia or worsening of metabolic control, respectively. In addition, some case reports have evidenced potential drug-drug interactions with various antihyperglycaemic agents that are usually associated with a higher risk of hypoglycaemia.
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References
Kahn SE. The relative contributions of insulin resistance and beta-cell dysfunction to the pathophysiology of type 2 diabetes. Diabetologia 2003; 46: 3–19
Scheen AJ. Pathophysiology of type 2 diabetes. Acta Clin Belg 2003; 58: 335–41
Scheen AJ, Lefbevre PJ. Oral antidiabetic agents: a guide to selection. Drugs 1998; 55: 225–36
Lebovitz HE. Oral therapies for diabetic hyperglycemia. Endocrinol Metab Clin N Am 2001; 30: 909–33
Inzucchi SE. Oral antihyperglycemic therapy for type 2 diabetes: scientific review. JAMA 2002; 287: 360–72
Charpentier G. Oral combination therapy for type 2 diabetes. Diabetes Metab Res Rev 2002; 18Suppl. 3: S70–6
Van Gaal LF, De Leeuw I. Rationale and options for combination therapy in the treatment of type 2 diabetes. Diabetologia 2003; 46Suppl. 1: M44–50
Scheen AJ. Current management of coexisting obesity and type 2 diabetes. Drugs 2003; 63: 1165–84
Hu G, Qiao Q, Tuomilehto J, et al. Prevalence of the metabolic syndrome and its relation to all-cause and cardiovascular mortality in nondiabetic European men and women. DECODE Study Group. Arch Intern Med 2004; 164: 1066–76
Grundy SM, Hansen B, Smith SC, et al. Clinical management of metabolic syndrome. Report of the American Heart Association/National Heart, Lung, and Blood Institute/American Diabetes Association: conference on scientific issues related to management. Circulation 2004; 109: 551–6
Scheen AJ. Management of the metabolic syndrome. Minerva Endocrinol 2004; 29: 31–45
Gaede P, Vedel P, Larsen N, et al. Multifactorial intervention and cardiovascular disease in patients with type 2 diabetes. N Engl J Med 2003; 348: 383–93
Gale E. The polypill and type 2 diabetes. Diabet Med 2004; 21: 8–10
Grant RW, Pirraglia PA, Meigs JB, et al. Trends in complexity of diabetes care in the United States from 1991 to 2000. Arch Intern Med 2004; 164: 1134–9
Scheen AJ, Lefebvre PJ. Antihyperglycaemic agents: drug interactions of clinical importance. Drug Saf 1995; 12: 32–45
Scheen AJ. Drug treatment of non-insulin-dependent diabetes mellitus in the 1990s: achievements and future developments. Drugs 1997; 54: 355–68
Krentz AJ, Ferner RE, Bailey CJ. Comparative tolerability profiles of oral antidiabetic agents. Drug Saf 1994; 11: 223–41
Davidson MB. Triple therapy: definitions, application, and treating to target. Diabetes Care 2004; 27: 1834–5
Ahmann AJ, Riddle MC. What to do when two oral agents fail to control type 2 diabetes: a matter of opinion or a matter of fact? Am J Med 2004; 116: 276–8
Rendell M. The role of sulphonylureas in the management of type 2 diabetes mellitus. Drugs 2004; 64: 1339–58
Riddle M. Combining sulfonylureas and other oral agents. Am J Med 2000; 108Suppl 6a: 15S–22S
Dunn CJ, Peters DH. Metformin: a review of its pharmacological properties and therapeutic use in non-insulin-dependent diabetes mellitus. Drugs 1995; 49: 721–49
Cusi K, DeFronzo RA. Metformin: a review of its metabolic effects. Diabetes Rev 1998; 6: 89–131
Setter SM, Iltz JL, Thams J, et al. Metformin hydrochloride in the treatment of type 2 diabetes mellitus: a clinical review with a focus on dual therapy. Clin Ther 2003; 25: 2991–3027
Hermann LS, Schersten B, Bitzen PO, et al. Therapeutic comparison of metformin and sulfonylurea, alone and in various combinations: a double-blind controlled study. Diabetes Care 1994; 17: 1100–9
Palmer KJ, Brodgen RN. Gliclazide, an update on its pharmacological properties and therapeutic efficacy in non-insulin-dependent diabetes mellitus. Drugs 1993; 46: 92–125
Mc Gavin JK, Perry CM, Goa KL. Gliclazide modified release. Drugs 2002; 62: 1357–64
Langtry HD, Balfour JA. Glimepiride: a review of its use in the management of type 2 diabetes mellitus. Drugs 1998; 55: 563–84
McCall AL. Clinical review of glimepiride. Expert Opin Pharmacother 2001; 2: 699–713
Massi-Nenedetti M. Glimepiride in type 2 diabetes mellitus: a review of the worldwide therapeutic experience. Clin Ther 2003; 25: 799–816
Charpentier G, Fleury F, Kabir M, et al. Improved glycaemic control by addition of glimepiride to metformin monotherapy in type 2 diabetic patients. Diabet Med 2001; 18: 828–34
Schernthaner G, Grimaldi A, Di Mario U, et al. GUIDE study: double-blind comparison of once-daily gliclazide MR and glimepiride in type 2 diabetic patients. Eur J Clin Invest 2004; 34: 535–42
Marathe PH, Arnold ME, Meeker J, et al. Pharmacokinetics and bioavailability of a metformin/glyburide tablet administered alone and with food. J Clin Pharmacol 2000; 40: 1494–502
Blonde L, Rosenstock J, Mooradian AD, et al. Glyburide/metformin combination product is safe and efficacious in patients with type 2 diabetes failing sulfonylurea therapy. Diabetes Obes Metab 2002; 4: 368–75
Garber AJ, Larsen J, Schneider SH, et al. Simultaneous glibenclamide/metformin therapy is superior to component monotherapy as an initial pharmacological treatment for type 2 diabetes. Diabetes Obes Metab 2002; 4: 201–8
Marre M, Howlett H, Lehert P, et al. Improved glycaemic control with metformin-glibenclamide combined tablet therapy (Glucovance®) in type 2 diabetic patients inadequately controlled with metformin. Diabet Med 2002; 19: 673–80
Garber AJ, Bruce S, Fiedorek FT. Durability of efficacy and long-term safety profile of glyburide/metformin tablets in patients with type 2 diabetes mellitus: an open-label extension study. Clin Ther 2002; 24: 1401–13
Goldstein BJ, Pans M, Rubin CJ. Multicenter, randomised, double-masked, parallel-group assessment of simultaneous glipizide/metformin as second-line pharmacologic treatment for patients with type 2 diabetes mellitus that is inadequately controlled by a sulfonylurea. Clin Ther 2003; 25: 890–903
UKPDS Prospective Diabetes Study Group. Effects of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). Lancet 1998; 352: 854–65
Mooradian AD, Chehade J. Implications of the UK Prospective Diabetes Study: questions answered and issues remaining. Drugs Aging 2000; 16: 159–64
Olsson J, Lindberg G, Gottsater M, et al. Increased mortality in type II diabetic patients using sulphonylurea and metformin in combination: a population-based observational study. Diabetologia 2000; 43: 558–60
Fisman EZ, Tenenbaum A, Boyko V, et al. Oral antidiabetic treatment in patients with coronary disease: time-related increased mortality on combined glyburide/metformin therapy over a 7.7-year follow-up. Clin Cardiol 2001; 24: 151–8
Mannucci E, Monami M, Masotti G, et al. All-cause mortality in diabetic patients treated with combinations of sulfonylureas and biguanides. Diabetes Metab Res Rev 2004; 20: 44–7
Braunstein S. New developments in type 2 diabetes mellitus: combination therapy with a thiazolidinedione. Clin Ther 2003; 25: 1895–917
Diamant M, Heine RJ. Thiazolidinediones in type 2 diabetes mellitus: current clinical evidence. Drugs 2003; 63: 1373–405
Meriden T. Progress with thiazolidinediones in the management of type 2 diabetes mellitus. Clin Ther 2004; 26: 177–90
Martens FMAC, Visseren FLJ, Lemay J, et al. Metabolic and additional vascular effects of thiazolidinediones. Drugs 2002; 62: 1463–80
Scheen AJ. Hepatotoxicity with thiazolidinediones: is it a class effect? Drug Saf 2001; 24: 873–88
Gillies PS, Dunn CJ. Pioglitazone. Drugs 2000; 60: 333–43
Chilcott J, Tappenden P, Jones ML, et al. A systematic review of the clinical effectiveness of pioglitazone in the treatment of type 2 diabetes mellitus. Clin Ther 2001; 23: 1792–823
Balfour JA, Plosker GL. Rosiglitazone. Drugs 1999; 57: 921–30
Wagstaff AJ, Goa KL. Rosiglitazone: a review of its use in the management of type 2 diabetes mellitus. Drugs 2002; 62: 1805–37
Kaneko T, Baba S, Toyota T. Dose finding study of AD-4833 in patients with NIDDM on treatment with a sulphonylurea drug: single blind comparative study of four dosages. Jpn J Clin Exp Med 1997; 74: 1278–306
Kaneko T, Baba S, Toyota T. Clinical evaluation of an insulinresistance improving agent, AD-4833, in patients with NIDDM on treatment with SU drug: a placebo controlled double blind clinical study. Jpn J Clin Exp Med 1997; 74: 1515–39
Kipnes MS, Krosnick A, Rendell MS, et al. Pioglitazone hydrochloride in combination with sulfonylurea therapy improves glycemic control in patients with type 2 diabetes mellitus: a randomised, placebo-controlled study. Am J Med 2001; 111: 10–7
Wolffenbuttel BH, Gomis R, Squatrito S, et al. Addition of low-dose rosiglitazone to sulphonylurea therapy improves glycaemic control in type 2 diabetic patients. Diabet Med 2000; 17: 40–7
Vongtharavat V, Wajchenberg BL, Waitman JN, et al. An international study of the effects of rosiglitazone plus sulphonylurea in patients with type 2 diabetes: 125 Study Group. Curr Med Res Opin 2002; 18: 456–61
Derosa G, Cicero AFG, Gaddi A, et al. Metabolic effects of pioglitazone and rosiglitazone in patients with diabetes and metabolic syndrome treated with glimepiride: a twelve-month, multicenter, double-blind, randomized, controlled, parallel-group trial. Clin Ther 2004; 26: 744–54
Inzucchi SE, Maggs DG, Spollett GR, et al. Efficacy and metabolic effects of metformin and troglitazone in type II diabetes mellitus. N Engl J Med 1998; 338: 867–72
Einhorn D, Rendell M, Rosenzweig J, et al. Pioglitazone hydrochloride in combination with metformin in the treatment of type 2 diabetes mellitus: a randomised, placebo-controlled study. The Pioglitazone 027 Study Group. Clin Ther 2000; 22: 1395–409
Fonseca V, Rosenstock J, Patwardhan R, et al. Effect of metformin and rosiglitazone combination therapy in patients with type 2 diabetes mellitus: a randomised controlled trial. JAMA 2000; 283: 1695–702
Gomez-Perez FJ, Fanghanel-Salmon G, Barbosa AJ, et al. Efficacy and safety of rosiglitazone plus metformin in Mexicans with type 2 diabetes. Diabetes Metab Res Rev 2002; 18: 127–34
Rendell M, Glazer NB, Ye Z. Combination therapy with pioglitazone plus metformin or sulfonylurea in patients with type 2 diabetes: influence of prior antidiabetic drug regimen. J Diabet Complications 2003; 17: 211–7
Hanefeld M, Brunetti P, Schernathaner GH, et al. One-year glycemic control with a sulfonylurea plus pioglitazone versus a sulfonylurea plus metformin in patients with type 2 diabetes. Diabetes Care 2004; 27: 141–7
Di Cicco RA, Allen A, Carr A, et al. Rosiglitazone does not alter the pharmacokinetics of metformin. J Clin Pharmacol 2000; 40: 1280–5
Clissold SP, Edwards C. Acarbose: a preliminary review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential. Drugs 1988; 35: 214–43
Balfour JA, McTavish D. Acarbose: an update of its pharmacology and therapeutic use in diabetes mellitus. Drugs 1993; 46: 1025–54
Salvatore T, Giugliano D. Pharmacokinetic-pharmacodynamic relationships of acarbose. Clin Pharmacokinet 1996; 30: 94–106
Scott LJ, Spencer CM. Miglitol: a review of its therapeutic potential in type 2 diabetes mellitus. Drugs 2000; 59: 521–49
Goke B, Fuder H, Wieckhorst G, et al. Voglibose (AO-128) is an efficient a-glucosidase inhibitor and mobilizes the endogenous GLP-1 reserve. Digestion 1995; 56: 493–501
Scheen AJ. Clinical efficacy of acarbose in the treatment of diabetes: a critical review of controlled trials. Diabetes Metab 1998; 24: 311–20
Breuer HW. Review of acarbose therapeutic strategies in the long-term treatment and in the prevention of type 2 diabetes. Int J Clin Pharmacol Ther 2003; 41: 421–40
Holman RR, Cull CA, Turner RC. A randomized double-blind trial of acarbose in type 2 diabetes shows improved glycemic control over 3 years (UK Prospective Diabetes Study 44). Diabetes Care 1999; 22: 960–4
Costa B, Pinol C. Acarbose in ambulatory treatment of noninsulin- dependent diabetes mellitus associated to imminent sulfonylurea failure: a randomised-multicentric trial in primary health care. Diabetes and Acarbose Research Group. Diabetes Res Clin Pract 1997; 38: 33–40
Willms B, Ruge D. Comparison of acarbose and metformin in patients with type 2 diabetes mellitus insufficiently controlled with diet and sulphonylureas: a randomised, placebo-controlled study. Diabet Med 1999; 16: 755–61
Johnston PS, Coniff RF, Hoogwerf BJ, et al. Effects of the carbohydrase inhibitor miglitol in sulfonylurea-treated NIDDM patients. Diabetes Care 1994; 17: 20–9
Johnston PS, Feig PU, Coniff RF, et al. Chronic treatment of African-American type 2 diabetic patients with a-glucosidase inhibition. Diabetes Care 1998; 21: 416–22
Matsumoto K, Sera Y, Abe Y, et al. Combination therapy of alpha-glucosidase inhibitor and a sulfonylurea compound prolongs the duration of good glycemic control. Metabolism 2002; 51: 1548–52
Gerard J, Lefebvre PJ, Luyckx AS. Glibenclamide pharmacokinetics in acarbose-treated type 2 diabetics. Eur J Clin Pharmacol 1984; 27: 233–6
Scheen AJ, Lefebvre PJ. Potential pharmacokinetics interferences between α-glucosidase inhibitors and other antidiabetic agents [letter]. Diabetes Care 2002; 25: 247–8
Kleist P, Ehrlich A, Suzuki Y, et al. Concomitant administration of the α-glucosidase inhibitor voglibose (AO-128) does not alter the pharmacokinetics of glibenclamide. Eur J Clin Pharmacol 1997; 53: 149–52
Scheen AJ. Clinical pharmacokinetics of metformin. Clin Pharmacokinet 1996; 30: 359–71
Scheen AJ, Ferreira Alves de Magalhaes C, Salvatore T, et al. Reduction of the acute bioavailability of metformin by the aglucosidase inhibitor acarbose in normal man. Eur J Clin Invest 1994; 24Suppl. 3: 50–4
Rosenstock J, Brown A, Fischer J, et al. Efficacy and safety of acarbose in metformin-treated patients with type 2 diabetes. Diabetes Care 1998; 21: 2050–5
Halimi S, Le Berre MA, Grange V. Efficacy and safety of acarbose add-on therapy in the treatment of overweight patients with type 2 diabetes inadequately controlled with metformin: a double-blind, placebo-controlled study.Diabetes Res Clin Pract 2000; 50: 49–56
Phillips P, Karrasch J, Scott R, et al. Acarbose improves glycemic control in overweight type 2 diabetic patients insufficiently treated with metformin. Diabetes Care 2003; 26: 269–73
Chiasson J-L, Naditch L. The synergistic effect of miglitol plus metformin combination therapy in the treatment of type 2 diabetes: Miglitol Canadian University Investigator Group. Diabetes Care 2001; 24: 989–94
Bando Y, Ushiogi Y, Okafuji K, et al. Troglitazone combination therapy in obese type 2 diabetic patients poorly controlled with alpha-glucosidase inhibitors. J Int Med Res 1999; 27: 53–64
Miller AK, Inglis AM, Thompson Culkin K, et al. The effect of acarbose on the pharmacokinetics of rosiglitazone. Eur J Clin Pharmacol 2001; 57: 105–9
Hayashi Y, Miyachi N, Takeuchi T, et al. Clinical evaluation of pioglitazone in patients with type 2 diabetes using aglucosidase inhibitor and examination of its efficacy profile. Diabetes Obes Metab 2003; 5: 58–65
Seino H, Yamaguchi H, Misaki A, et al. Clinical effect of combination therapy of pioglitazone and an alpha-glucosidase inhibitor. Curr Med Res Opin 2003; 19: 675–82
Dornhorst A. Insulinotropic meglitinide analogues. Lancet 2001; 358: 1709–16
Owens DR. Repaglinide: prandial glucose regulator: a new class of oral antidiabetic drug. Diabet Med 1998; 15Suppl. 4: S28–36
Cully CR, Jarvis B. Repaglinide: a review of its therapeutic use in type 2 diabetes mellitus. Drugs 2001; 61: 1625–60
Dunn CJ, Faulds D. Nateglinide. Drugs 2000; 60: 607–15
Norman P, Rabasseda X. Nateglinide: a structurally novel insulin secretion agent. Drugs Today (Barc) 2001; 37Suppl. F: 1–16
McLeod JF. Clinical pharmacokinetics of nateglinide: a rapidlyabsorbed, short-acting insulinotropic agent. Clin Pharmacokinet 2004; 43: 97–120
Moses R. Repaglinide in combination therapy. Diabetes Nutr Metab 2002; 15(6 Suppl.): 33–8
Moses R, Slobodniuk R, Boyages S, et al. Effect of repaglinide addition to metformin monotherapy on glycemic control in patients with type 2 diabetes. Diabetes Care 1999; 22: 119–24
Hirshberg Y, Karara AH, Pietri AO, et al. Improved control of mealtime glucose excursions with coadministration of nateglinide and metformin. Diabetes Care 2000; 23: 349–53
Horton ES, Clinkingbeard C, Galtin M, et al. Nateglinide alone and in combination with metformin improves glycemic control by reducing mealtime glucose levels in type 2 diabetes. Diabetes Care 2000; 23: 1660–5
Marre M, Van Gaal L, Usadel KH, et al. Nateglinide improves glycaemic control when added to metformin monotherapy: results of a randomized trial with type 2 diabetes patients. Diabetes Obes Metab 2002; 4: 177–86
Salas M, Ward A, Caro J. Health and economic effects of adding nateglinide to metformin to achieve dual control of glycosylated hemogobin and postprandial glucose levels in a model of type 2 diabetes mellitus. Clin Ther 2002; 24: 1690–705
Raskin P, Klaff L, McGill S, et al. Efficacy and safety of combination therapy: repaglinide plus metformin versus nateglinide plus metformin. Diabetes Care 2003; 26: 2063–8
Raskin P, Jovanovic L, Berger S, et al. Repaglinide-troglitazone combination therapy: improved glycemic control in type 2 diabetes. Diabetes Care 2000; 23: 979–83
Rosenstock J, Shen SG, Gatlin MR, et al. Combination therapy with nateglinide and a thiazolidinedione improves glycemic control in type 2 diabetes. Diabetes Care 2002; 25: 1529–33
Jovanovic L, Hassman DR, Gooch B, et al. Treatment of type 2 diabetes with a combination regimen of repaglinide plus pioglitazone: Repaglinide/Pioglitazone Study Group. Diabetes Res Clin Pract 2004; 63: 127–34
Gavin LA, Barth J, Arnold D, et al. Troglitazone add-on therapy to a combination of sulphonylureas plus metformin achieved and sustained effective diabetes control. Endocr Pract 2000; 6: 305–10
Yale J, Valiquett T, Ghazzi M, et al. The effect of a thiazolidinedione drug, troglitazone, on glycemia in patients with type 2 diabetes poorly controlled with sulphonylurea and metformin: a multicenter, randomized, double-blind, placebo-controlled trial. Troglitazone Triple-Therapy Study Group. Ann Intern Med 2001; 134: 737–45
Aljabri K, Kozak SE, Thompson DM. Addition of pioglitazone or bedtime insulin to maximal doses of sulfonylurea and metformin in type 2 diabetes patients with poor glucose control: a prospective, randomized trial. Am J Med 2004; 116: 230–5
Kiayias JA, Vlachou ED, Theodosopoulou E, et al. Rosiglitazone in combination with glimepiride plus metformin in type 2 diabetic patients. Diabetes Care 2002; 25: 1251–2
Bell DSH, Ovalle F. Long-term efficacy of triple oral therapy for type 2 diabetes mellitus. Endocr Pract 2002; 8: 271–5
Roy R, Navar M, Palomeno G, et al. Real world effectiveness of rosiglitazone added to maximal (tolerated) doses of metformin and a sulfonylurea agent: a systematic evaluation of triple oral therapy in a minority population. Diabetes Care 2004; 27: 1741–2
Dailey GE, Noor MA, Park J-S, et al. Glycemic control with glyburide/metformin tablets in combination with rosiglitazone in patients with type 2 diabetes: a randomized, double-blind trial. Am J Med 2004; 116: 223–9
Schwartz S, Sievers R, Strange P, et al. Insulin 70/30 mix plus metformin versus triple oral therapy in the treatment of type 2 diabetes after failure of two oral drugs: efficacy, safety, and cost-analysis. Diabetes Care 2003; 26: 2238–43
Brian WR. Hypoglycemic agents. In: Levy RH, Thummel KE, Trager WF, et al, editors. Metabolic drug interactions. Philadelphia (PA): Lippincott Williams & Wilkins, 2000: 529–43
Marks V, Teale JD. Drug-induced hypoglycemia. Endocrinol Metab Clin North Am 1999; 28: 555–77
Holstein A, Egberts EH. Risk of hypoglycaemia with oral antidiabetic agents in patients with type 2 diabetes. Exp Clin Endocrinol Diabetes 2003; 111: 405–14
Collin M, Mucklow JC. Drug interactions, renal impairment and hypoglycaemia in a patient with type II diabetes. Br J Clin Pharmacol 1999; 48: 134–7
Williams D, Feely J. Pharmacokinetic-pharmacodynamic drug interactions with HMG-CoA reductase inhibitors. Clin Pharmacokinet 2002; 41: 343–70
Shorr RI, Ray WA, Daugherty JR, et al. Antihypertensives and the risk of serious hypoglycemia in old persons using insulin or sulfonylureas. JAMA 1997; 278: 40–3
Fichtenbaum CJ, Gerber JG. Interactions between antiretroviral drugs and drugs used for the therapy of the metabolic complications encountered during HIV infection. Clin Pharmacokinet 2002; 41: 1195–211
Melkersson K, Dahl M-L. Adverse metabolic effects associated with atypical antipsychotics: literature review and clinical implications. Drugs 2004; 64: 701–23
DeVane CL, Markowitz JS. Psychoactive drug interactions with pharmacotherapy for diabetes. Psychopharmacol Bull 2002; 36: 40–52
Haffner SM. Statin therapy for the treatment of diabetic dyslipidemia. Diabetes Metab Res Rev 2003; 19: 280–7
Vijan S, Hayward RA. Pharmacologic lipid-lowering therapy in type 2 diabetes mellitus: background paper from the American College of Physicians. Ann Intern Med 2004; 140: 650–8
Snow V, Aronson MD, Hornbake ER, et al. Lipid control in the management of type 2 diabetes mellitus: a clinical practice guideline from the American College of Physicians. Ann Intern Med 2004; 140: 644–9
Steiner G. Fibrates in the metabolic syndrome and in diabetes. Endocrinol Metab Clin North Am 2004; 33: 545–55
Bellosta S, Paoletti R, Corsini A. Safety of statins: focus on clinical pharmacokinetics and drug interactions. Circulation 2004; 109Suppl. III: III–50–7
Martin J, Krum H. Cytochrome P450 drug interactions within the HMG-CoA reductase inhibitor class: are they clinically relevant? Drug Saf 2003; 26: 13–21
Johnson BF, LaBelle P, Wilson J, et al. Effects of lovastatin in diabetic patients treated with chlorpropamide. Clin Pharmacol Ther 1990; 48: 467–72
Appel S, Rufenacht T, Kalafsky G, et al. Lack of interaction between fluvastatin and oral hypoglycaemic agents in healthy subjects and in patients with non-insulin-dependent diabetes mellitus. Am J Cardiol 1995; 76: 29A–32A
Hatorp V, Hansen KT, Thomsen MS. Influence of drugs interacting with CYP3A4 on the pharmacokinetics, pharmacodynamics, and safety of the prandial glucose regulator repaglinide. J Clin Pharmacol 2003; 43: 649–60
Sahi J, Black CB, Hamilton GA, et al. Comparative effects of thiazolidinediones on in vitro P450 enzyme induction and inhibition. Drug Metab Dispos 2003; 31: 439–46
Klotz U, Sailer D. Drug interactions: their impact on safe drug therapy in the example of the new thiazolidinedione group (glitazone) [in German]. Arzneimittel Forschung 2001; 51: 112–7
Ramachandran V, Kostrubsky VE, Komoroski BJ, et al. Troglitazone increases cytochrome P-450 3A protein and activity in primary cultures of human hepatocytes. Drug Metab Dispos 1999; 27: 1194–9
DiTusa L, Luzier AB. Potential interaction between troglitazone and atorvastatin. J Clin Pharm Ther 2000; 25: 279–82
Prueksaritanont T, Vega JM, Zhao J, et al. Interactions between simvastatin and troglitazone or pioglitazone in healthy subjects. J Clin Pharmacol 2001; 41: 573–81
Alsheikh-Ali AA, Abourjaily HM, Karas RH. Risk of adverse events with concomitant use of atorvastatin or simvastatin and glucose-lowering drugs (thiazolidinediones, metformin, sulfonylurea, insulin and acarbose). Am J Cardiol 2002; 89: 1308–10
Alsheikh-Ali AA, Karas RH. Adverse events with concomitant use of simvastatin or atorvastatin and thiazolidinediones. Am J Cardiol 2004; 93: 1417–8
Cox PJ, Ryan DA, Hollis FJ, et al. Absorption, disposition, and metabolism of rosiglitazone, a potent thiazolidinedione insulin sensitizer, in humans. Drug Metab Dispos 2000; 28: 772–80
Eckland DA, Danhof M. Clinical pharmacokinetics of pioglitazone. Exp Clin Endocrinol Diab 2000; 108Suppl. 2: S234–42
Freed MI, Ratner R, Marcovina SM, et al. Effects of rosiglitazone alone and in combination with atorvastatin on the metabolic abnormalities in type 2 diabetes mellitus. Am J Cardiol 2002; 90: 947–52
Glazer NB, Cheatham WW. Thiazolidinediones for type 2 diabetes: no evidence exists that pioglitazone induces hepatic cytochrome P450 isoform CYP3A4 [letter]. BMJ 2001; 322: 235–6
Lewin AJ, Kipnes MS, Meneghini LF, et al. Effects of simvastatin on the lipid profile and attainment of low-density lipoprotein cholesterol goals when added to thiazolidinedione therapy in patients with type 2 diabetes mellitus: a multicenter, randomized, double-blind, placebo-controlled trial. Clin Ther 2004; 26: 379–89
Backman JT, Kyrklund C, Neuvonen M, et al. Gemfibrozil greatly increases plasma concentrations of cerivastatin. Clin Pharmacol Ther 2002; 72: 685–91
Niemi M, Neuvonen PJ, Kivisto KT. Effect of gemfibrozil on the pharmacokinetics and pharmacodynamics of glimepiride. Clin Pharmacol Ther 2001; 70: 439–45
Niemi M, Backman JT, Neuvonen M, et al. Effects of gemfibrozil, itraconazole, and their combination on the pharmacokinetics and pharmacodynamics of repaglinide: potentially hazardous interaction between gemfibrozil and repaglinide. Diabetologia 2003; 46: 347–51
Kajosaari LI, Backman JT, Neuvonen M, et al. Lack of effect of bezafibrate and fenofibrate on the pharmacokinetics and pharmacodynamics of repaglinide. Br J Clin Pharmacol 2004; 58: 390–6
Niemi M, Backman JT, Granfors M, et al. Gemfibrozil considerably increases the plasma concentrations of rosiglitazone. Diabetologia 2003; 46: 1319–23
Jones NP, Mather RA, Sautter M. Rosiglitazone treatment does not impair the triglyceride-lowering activity of fibrates in patients with type 2 diabetes mellitus [abstract]. Diabetes 2000; 49Suppl. 1: A359, 1507-PO
Sowers JR, Epstein M, Frohlich ED. Diabetes, hypertension, and cardiovascular disease. Hypertension 2001; 37: 1053–9
Padwal R, Laupacis A. Antihypertensive therapy and incidence of type 2 diabetes: a systematic review. Diabetes Care 2004; 27: 247–55
Tse WY, Kendall M. Is there a role for beta-blockers in hypertensive diabetic patients? Diabet Med 1994; 11: 137–44
Herings RM, de Boer A, Stricker BH, et al. Hypoglycaemia associated with use of inhibitors of angiotensin converting enzyme. Lancet 1995; 345: 1195–8
Kaplan NM. Management of hypertension in patients with type 2 diabetes mellitus: guidelines based on current evidence. Ann Intern Med 2001; 135: 1079–83
Carey RM, Siragy HM. Newly recognized components of the renin-angiotensin system: potential roles in cardiovascular and renal regulation. Endocr Rev 2003; 24: 261–71
Arauz-Pacheco C, Ramirez LC, Rios JM, et al. Hypoglycaemia induced by angiotensin-converting enzyme inhibitors in patients with non-insulin-dependent diabetes receiving sulfonylurea therapy. Am J Med 1990; 89: 811–3
Moore N, Kreft-Jais C, Haramburu F, et al. Reports of hypoglycaemia associated with the use of ACE inhibitors and other drugs: a case/non-case study in the French pharmacovigilance system database. Br J Clin Pharmacol 1997; 44: 513–8
Girardin E, Raccah D. Interaction between converting enzyme inhibitors and hypoglycemic sulfonamides or insulin [in French]. Presse Med 1998; 27: 1914–23
Morris AD, Boyle DI, McMahon AD, et al. ACE inhibitor use is associated with hospitalization for severe hypoglycaemia in patients with diabetes: DARTS/MEMO Collaboration. Diabetes Care 1997; 20: 1363–7
Scheen AJ. Prevention of type 2 diabetes through inhibition of the renin-angiotensin system. Drugs 2004; 64(22): 2537–65
The DREAM Trial Investigators. Rationale, design and recruitment characteristics of a large, simple international trial of diabetes prevention: the DREAM trial. Diabetologia 2004; 47: 1519–27
Ashcroft FM, Gribble FM. ATP-sensitive K+ channels and insulin secretion: their role in health and disease. Diabetologia 1999; 42: 903–19
Gribble FM, Reimann F. Differential selectivity of insulin secretagogues: mechanisms, clinical implications, and drug interactions. J Diabetes Complications 2003; 17: 11–5
Dhindsa P, Davis KR, Donnelly R. Comparison of the microand macro-vascular effects of glimepriride and gliclazide in metformin-treated patients with type 2 diabetes: a double-bind, crossover study. Br J Clin Pharmacol 2003; 55: 616–9
Riveline JP, Danchin N, Ledru F, et al. Sulfonylureas and cardiovascular effects: from experimental data to clinical use. Available data in humans and clinical applications. Diabetes Metab 2003; 29: 207–22
Hata N, Takano M, Kunimi T, et al. Lack of antagonism between nicorandil and sulfonylurea in stable angina pectoris. Int J Clin Pharmacol Res 2001; 21: 59–63
Dresser GK, Spence JD, Bailey DG. Pharmacokinetic-pharmacodynamic consequences and clinical relevance of cytochrome P450 3A4 inhibition. Clin Pharmacokinet 2000; 38: 41–57
Niemi M, Backman JT, Neuvonen M, et al. Effect of rifampicin on the pharmacokinetics and pharmacodynamics of glyburide and glipizide. Clin Pharmacol Ther 2001; 69: 400–6
Park JY, Kim KA, Park PW, et al. Effect of rifampicin on the pharmacokinetics and pharmacodynamics of gliclazide. Clin Pharmacol Ther 2003; 74: 334–40
Niemi M, Kivisto KT, Backman JT, et al. Effect of rifampicin on the pharmacokinetics and pharmacodynamics of glimepiride. Br J Clin Pharmacol 2000; 50: 591–5
Niemi M, Backman JT, Neuvonen M, et al. Rifampicin decreases the plasma concentrations and effects of repaglinide. Clin Pharmacol Ther 2000; 68: 495–500
Niemi M, Backman JT, Neuvonen M, et al. Effect of rifampicin on the pharmacokinetics and pharmacodynamics of nateglinide in healthy subjects. Br J Clin Pharmacol 2003; 56: 427–32
Park JY, Kim KA, Kang MH, et al. Effect of rifampicin on the pharmacokinetics of rosiglitazone in healthy subjects. Clin Pharmacol Ther 2004; 75: 157–62
Niemi M, Backman JT, Neuvonen PJ. Effects of trimethoprim and rifampin on the pharmacokinetics of the cytochrome P450 2C8 substrate rosiglitazone. Clin Pharmacol Ther 2004; 76: 239–49
Niemi M, Backman JT, Neuvonen M, et al. Effect of fluconazole and fluvoxamine on the pharmacokinetics and pharmacodynamics of glimepiride. Clin Pharmacol Ther 2001; 69: 194–200
Hatorp V, Thomsen MS. Drug interaction studies with repaglinide: repaglinide on digoxin or theophylline pharmacokinetics and cimetidine on repaglinide pharmacokinetics. J Clin Pharmacol 2000; 40: 184–92
Niemi M, Kajosaari LI, Neuvonen M, et al. The CYP2C8 inhibitor trimethoprim increases the plasma concentrations of repaglinide in healthy subjects. Br J Clin Pharmacol 2004; 57: 441–7
Niemi M, Neuvonen PJ, Kivisto KT. The cytochrome P450 3A4 inhibitor clarithromycin increases the plasma concentrations and effects of repaglinide. Clin Pharmacol Ther 2001; 70: 58–65
Niemi M, Neuvonen M, Juntti Patinen L, et al. Effect of fluconazole on the pharmacokinetics and pharmacodynamics of nateglinide. Clin Pharmacol Ther 2003; 74: 25–31
Sabia H, Sunkara G, Ligueros-Saylan M, et al. Effect of a selective CYP2C9 inhibitor on the pharmacokinetics of nateglinide in healthy subjects. Eur J Clin Pharmacol 2004; 60: 407–12
Miller AK, Di Cicco RA, Freed MI. The effect of ranitidine on the pharmacokinetics of rosiglitazone in healthy adult male volunteers. Clin Ther 2002; 24: 1062–71
Serrano JS, Jimenez CM, Serrano MI, et al. A possible interaction of potential clinical interest between digoxin and acarbose. Clin Pharmacol Ther 1996; 60: 589–92
Miura T, Ueno K, Tanaka K, et al. Impairment of absorption of digoxin by acarbose. J Clin Pharmacol 1998; 38: 654–7
Ben-Ami H, Krivoy N, Nagachandran P, et al. An interaction between digoxin and acarbose [letter]. Diabetes Care 1999; 22: 860–1
Cohen E, Almog S, Staruvin D, et al. Do therapeutic doses of acarbose alter the pharmacokinetics of digoxin? Isr Med Assoc J 2002; 4: 772–5
Morreale AP, Janetzky K. Probable interaction of warfarin and acarbose [letter]. Am J Health Syst Pharm 1997; 54: 1551–2
Schall R, Muller FO, Hundt HKL, et al. Study of the effects of miglitol on the pharmacokinetics and pharmacodynamics of warfarin in healthy males. Arzneimittel Forschung 1996; 46: 41–6
Kusumoto M, Ueno K, Fujimura Y, et al. Lack of kinetic interaction between digoxin and voglibose [letter]. Eur J Clin Pharmacol 1999; 55: 79–80
Nagai Y, Hayakawa T, Abe T, et al. Are there different effects of acarbose and voglibose on serum levels of digoxin in a diabetic patient with congestive heart failure? [letter]. Diabetes Care 2000; 23: 1703
Fuder H, Kleist P, Birkel M, et al. The α-glucosidase inhibitor voglibose (A0-128) does not change pharmacodynamics or pharmacokinetics of warfarin. Eur J Clin Pharmacol 1997; 53: 153–7
Kortboyer JM, Eckland D. Pioglitazone has low potential for drug interactions [abstract]. Diabetologia 1999; 42Suppl. 1: A228
Di Cicco RA, Miller AK, Patterson S, et al. Rosiglitazone does not affect the steady-state pharmacokinetics of digoxin. J Clin Pharmacol 2000; 40: 1516–21
Rosenberg MA, Strange P, Cohen A. Assessment of pharmacokinetic and pharmacodynamic interaction between warfarin and repaglinide [abstract]. Diabetes 1999; 48Suppl. 1: A356
Zhou H, Walter YH, Smith H, et al. Nateglinide, a new mealtime glucose regulator: lack of pharmacokinetic interaction with digoxin in healthy volunteers. Clin Drug Invest 2000; 19: 465–71
Sunkara G, Bigler H, Wang Y, et al. The effect of nateglinide on the pharmacokinetics and pharmacodynamics of acenocoumarol. Curr Med Res Opin 2004; 20: 41–8
Jetter A, Kinzig-Schippers M, Skott A, et al. Cytochrome P450 2C9 phenotyping using low-dose tolbutamide. Eur J Clin Pharmacol 2004; 60: 165–71
Shon JH, Yoon YR, Kim KA, et al. Effects of CYP2C19 and CYP2C9 genetic polymorphisms on the disposition of and blood glucose lowering response to tolbutamide in humans. Pharmacogenetics 2002; 12 111–9
Kirchheiner J, Bauer S, Meineke I, et al. Impact of CYP2C9 and CYP2C19 polymorphisms on tolbutamide kinetics and the insulin and glucose response in healthy volunteers. Pharmacogenetics 2002; 12: 101–9
Kirchheiner J, Brockmoller J, Meineke I, et al. Impact of CYP2C9 amino acid polymorphisms on glyburide kinetics and on the insulin and glucose response in healthy volunteers. Clin Pharmacol Ther 2002; 71: 286–96
Niemi M, Cascorbi I, Timm R, et al. Glyburide and glimepiride pharmacokinetics in subjects with different CYP2C9 genotypes. Clin Pharmacol Ther 2002; 72: 326–32
Miners JO, Birkett DJ. Cytochrome P4502C9: an enzyme of major importance in human drug metabolism. Br J Clin Pharmacol 1998; 45: 525–38
Niemi M, Backman JT, Fromm MF, et al. Pharmacokinetic interactions with rifampicin: clinical relevance. Clin Pharmacokinet 2003; 42: 819–50
Finch CK, Chrisman CR, Baciewicz AM, et al. Rifampin and rifabutin drug interactions: an update. Arch Intern Med 2002; 162: 985–92
Surekha V, Peter JV, Jeyaseelan L, et al. Drug interaction: rifampicin and glibenclamide. Natl Med J India 1997; 10: 11–2
Greiner B, Eichelbaum M, Fritz P, et al. The role of intestinal Pglycoprotein in the interaction of digoxin and rifampin. J Clin Invest 1999; 104: 147–53
Goldstein PE, Boom A, van Geffel J, et al. P-glycoprotein inhibition by glibenclamide and related compounds. Pflugers Arch Eur J Physiol 1999; 437: 652–60
Odeh M, Oliven A. Doxycyline-induced hypoglycaemia. J Clin Pharmacol 2000; 40: 1173–4
Roberge RJ, Kaplan R, Frank R, et al. Glyburide-ciprofloxacin interaction with resistant hypoglycemia. Ann Emerg Med 2000; 36: 160–3
Menzies DJ, Dorsainvil PA, Cunha BA, et al. Severe and persistent hypoglycemia due to gatifloxacin interaction with oral hypoglycemic agents. Am J Med 2002; 113: 232–4
Lee K, Mize R, Lowenstein SR. Glyburide-induced hypoglycaemia and ranitidine. Ann Intern Med 1987; 107: 261–2
Kubacka RT, Antal EJ, Juhl RP. The paradoxical effect of cimetidine and ranitidine on glibenclamide pharmacokinetics and pharmacodynamics. Br J Clin Pharmacol 1987; 23: 743–51
Islam SI, Masuda QN, Bolaji OO, et al. Possible interaction between cyclosporine and glibenclamide in posttransplant diabetic patients. Ther Drug Monit 1996; 18: 624–6
Muck W, Heine PR, Breuel HP, et al. The effect of multiple oral dosing of nimodipine on glibenclamide pharmacodynamics and pharmacokinetics in elderly patients with type-2 diabetes mellitus. Int J Clin Pharmacol Ther 1995; 33: 89–94
Boni JP, Cevallos WH, DeCleene S, et al. The influence of bromfenac on the pharmacokinetics and pharmacodynamic responses to glyburide in diabetic subjects. Pharmacotherapy 1997; 17: 783–90
Gleiter CH, Schreeb KH, Freudenthale S, et al. Lack of interaction between thioctic acid, glibenclamide and acarbose. Br J Clin Pharmacol 1999; 48: 819–25
van Giersbergen PLM, Treiber A, Clozel M, et al. In vivo and in vitro studies exploring the pharmacokinetic interaction between bosentan, a dual endothelin receptor antagonist, and glyburide. Clin Pharmacol Ther 2002; 71: 253–62
Martin DE, DeCherney GS, Ilson BE, et al. Eprosartan, an angiotensin II receptor antagonist, does not affect the pharmacodynamics of glyburide in patients with type II diabetes mellitus. J Clin Pharmacol 1997; 37: 155–9
Feely J, Collins WC, Cullen M, et al. Potentiation of the hypoglycaemic response to glipizide in diabetic patients by histamine H2-receptor antagonists. Br J Clin Pharmacol 1993; 35: 321–3
Chidester PD, Connito DJ. Interaction between glipizide and cyclosporine: report of two cases. Transplant Proc 1993; 25: 2136–7
Sagedal S, Asberg A, Hartmann A, et al. Glipizide treatment of post-transplant diabetes does not interfere with cyclosporine pharmacokinetics in renal allograft recipients. Clin Transplant 1998; 12: 553–6
Kihara Y, Otsuki M. Interaction of gliclazide and rifampicin [letter]. Diabetes Care 2000; 23: 1204–5
Abad S, Moachon L, Blanche P, et al. Possible interaction between gliclazide, fluconazole and sulfamethoxazole resulting in severe hypoglycaemia. Br J Clin Pharmacol 2001; 52: 456–7
Holstein A, Plaschke A, Hammer C, et al. Characteristics and time course of severe glimepiride- versus glibenclamide-induced hypoglycaemia. Eur J Clin Pharmacol 2003; 59: 91–7
Klepser TB, Kelly MW. Metformin hydrochloride: an antihyperglycemic agent. Am J Health Syst Pharm 1997; 54: 893–903
Howlett HCS, Bailey CJ. A risk-benefit assessment of metformin in type 2 diabetes mellitus. Drug Saf 1999; 20: 489–503
Somogyi A, Stockley C, Keal J. Reduction of metformin renal tubular secretion by cimetidine in man. Br J Clin Pharmacol 1987; 23: 545–51
Richardt D, Rosmarin C, Havlik I, et al. No effect of miglitol on the oral bioavailability of single-dose phenytoin in healthy males. Clin Drug Invest 1997; 13: 171–4
Farley-Hills E, Sivasankar R, Martin M. Fatal liver failure associated with pioglitazone [letter]. BMJ 2004; 329: 429
Scheen AJ, Luyckx FH. Liver disease in obesity. Best Pract Res Clin Endocrinol Metab 2002; 16: 703–16
Jick SS, Stender M, Myers MW. Frequency of liver disease in type 2 diabetic patients treated with oral antidiabetic agents. Diabetes Care 1999; 22: 2067–71
Belcher G, Lambert C, Edwards GC, et al. Results of liver safety testing in 3713 type 2 diabetic patients treated for one year in double blind controlled trials with pioglitazone, metformin or gliclazide [abstract]. Diabetologia 2003; 4Suppl. 2: A291
Lebovitz HE, Kreider M, Freed MI. Evaluation of liver function in type 2 diabetic patients during clinical trials: evidence that rosiglitazone does not cause hepatic dysfunction. Diabetes Care 2002; 25: 815–21
Scheen AJ. Combined thiazolidinedione-insulin therapy: should we be concerned about safety? Drug Saf 2004; 27: 841–56
Yamazaki H, Suzuki M, Tane K, et al. In vitro inhibitory effects of troglitazone and its metabolites on drug oxidation activities of human cytochrome P450 enzymes: comparison with pioglitazone and rosiglitazone. Xenobiotica 2000; 30: 61–70
Kaplan B, Friedman G, Jacobs M, et al. Potential interaction of troglitazone and cyclosporine. Transplantation 1998; 65: 1399–400
Glazer NB, Cheatham WW. Thiazolididiones for type 2 diabetes: no evidence exists that pioglitazone induces hepatic cytochrome P450 isoform CYP3A4 [letter]. BMJ 2001; 322: 252–3
Carey R, Liu Y. Pioglitazone does not markedly alter oral contraceptive or hormone replacement pharmacokinetics [abstract]. Diabetes 2000; 49Suppl. 1: A340–1
Baldwin SJ, Clarke SE, Chenery RJ. Characterization of the cytochrome P450 enzymes involved in the in vitro metabolism of rosiglitazone. Br J Clin Pharmacol 1999; 48: 424–32
Rao MN, Mullangi R, Katneni K, et al. Lack of effect of sucralfate on the absorption and pharmacokinetics of rosiglitazone. J Clin Pharmacol 2002; 42: 670–5
Thompson KA, Miller AK, Inglis AML, et al. Rosiglitazone does not markedly alter CYP3A4-mediated drug metabolism [abstract]. Diabetologia 1999; 42Suppl. 1: A227
Harris RZ, Inglis AML, Miller AK, et al. Rosiglitazone has no clinically significant effect on nifedipine pharmacokinetics. J Clin Pharmacol 1999; 39: 1189–94
Inglis A, Miller A, Culkin K, et al. Lack of effect of rosiglitazone on the pharmacokinetics of oral contraceptives in healthy female volunteers. J Clin Pharmacol 2001; 41: 683–90
Hatorp V. Clinical pharmacokinetics and pharmacodynamics of repaglinide. Clin Pharmacokinet 2002; 41: 471–83
Plum A, Muller LK, Jansen JA. The effects of selected drugs on the in vitro protein binding of repaglinide in human plasma. Methods Find Exp Clin Pharmacol 2000; 22: 139–43
Bidstrup TB, Bjornsdottir I, Sidelman UG, et al. CYP2C8 and CYP3A4 are the principal enzymes involved in the human in vitro biotransformation of the insulin secretagogue repaglinide. Br J Clin Pharmacol 2003; 56: 305–14
Niemi M, Leathart JB, Neuvonen M, et al. Polymorphism in CYP2C8 is associated with reduced plasma concentrations of repaglinide. Clin Pharmacol Ther 2003; 74: 380–7
Schwietert R, Wemer J, Jonkman JHG, et al. No change in repaglinide pharmacokinetics with cimetidine co-administration [abstract]. Eur J Clin Pharmacol 1997; 52: A140
Schwietert R, Wemer J, Jonkman JHG, et al. Co-administration of repaglinide does not affect digoxin pharmacokinetics [abstract]. Eur J Clin Pharmacol 1997; 52: A140
Weaver ML, Orwig BA, Rodriguez LC, et al. Pharmacokinetics and metabolism of nateglinide in humans. Drug Metab Dispos 2001; 29: 415–21
Kirchheiner J, Meineke I, Muller G, et al. Influence of CYP2C9 and CYP2D6 polymorphisms on the pharmacokinetics of nateglinide in genotyped healthy volunteers. Clin Pharmacokinet 2004; 43: 267–78
Anderson D, Shelley S, Crick N, et al. A 3-way crossover study to evaluate the pharmacokinetic interaction between nateglinide and diclofenac in healthy volunteers. Int J Clin Pharmacol Ther 2002; 40: 457–64
Anderson D, Shelley S, Crick N, et al. No effect of the novel antidiabetic agent nateglinide on the pharmacokinetics and anticoagulant properties of warfarin in healthy volunteers. J Clin Pharmacol 2002; 42: 1358–65
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Scheen, A.J. Drug Interactions of Clinical Importance with Antihyperglycaemic Agents. Drug Saf 28, 601–631 (2005). https://doi.org/10.2165/00002018-200528070-00004
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DOI: https://doi.org/10.2165/00002018-200528070-00004