Drug Safety

, Volume 30, Issue 9, pp 741–753 | Cite as

Thiazolidinediones and their Fluid-Related Adverse Effects

Facts, Fiction and Putative Management Strategies
Practical Drug Safety


Thiazolidinediones (TZDs) or glitazones are agents that are widely used for the treatment of type 2 diabetes mellitus. These drugs have a multitude of therapeutic effects including reduction in insulin resistance and hyperglycaemia, anti-inflammatory effects and amelioration of hypertension, microalbuminuria and hepatic steatosis.

The TZD molecular target, peroxisome proliferator-activated receptor γ (PPARγ), a nuclear transcription factor, is expressed diffusely in humans, including many tissues comprising the cardiovascular and renal systems. This suggests a potential for TZDs to elicit perturbing effects on these systems, which are independent of their effects on glucose and lipid metabolism.

One of the most common adverse effects of TZDs is fluid retention, which can result in, or exacerbate, oedema and congestive heart failure (CHF). The frequency of peripheral oedema is approximately 5% when TZDs are used in mono-or combination oral therapy, and about 15% when used with insulin.

Patients with type 2 diabetes are at high risk of myriad morbid complications, including CHF. The development of CHF, particularly in the elderly, is a harbinger of premature mortality. TZD-induced oedema is largely peripheral, may have its origins in changes in haemodynamics, with some contribution from molecules, which regulate cell and tissue permeability (e.g. vascular endothelial growth factor and protein kinase Cβ), and remains the preponderant manifestation of TZD-induced fluid retention even in those with existing heart failure. Preclinical and pilot clinical data attest to the fact that at least part of the fluid retention derives from a direct effect of TZDs on sodium reabsorption via the renal medullary collecting duct, a mechanism that is sensitive to diuretic agents that have this nephron segment as their site of action, in whole or in part (spironolactone, amiloride and hydrochlorothiazide). Our review suggests various potential clinical strategies by which TZD-induced fluid retention might be effectively monitored and addressed.


Congestive Heart Failure Metformin Rosiglitazone Pioglitazone Brain Natriuretic Peptide 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



No sources of funding were used to assist in the preparation of this review. Dr Karalliedde has received honoraria for lectures and grant support from GlaxoSmithKline, the manufacturer of rosiglitazone. Dr Buckingham is a former employee of, and stockholder in, GlaxoSmithKline.


  1. 1.
    Lehmann JM, Moore LB, Smith-Oliver TA, et al. An antidiabetic thiazolidinedione is a high affinity ligand for peroxisome proliferator-activated receptor γ (PPARγ). J Biol Chem 1995 Jun 2; 270(22): 12953–6PubMedCrossRefGoogle Scholar
  2. 2.
    Chojkier M. Troglitazone and liver injury: in search of answers. Hepatology 2005; 41(2): 237–46PubMedCrossRefGoogle Scholar
  3. 3.
    Neuschwander-Tetri BA, Brunt EM, Wehmeier KR, et al. Improved nonalcoholic steatohepatitis after 48 weeks of treatment with the PPAR-γ ligand rosiglitazone. Hepatology 2003; 38(4): 1008–17PubMedGoogle Scholar
  4. 4.
    Promrat K, Lutchman G, Uwaifo GI, et al. A pilot study of pioglitazone treatment for non-alcoholic steatohepatitis. Hepatology 2004; 39(1): 188–96PubMedCrossRefGoogle Scholar
  5. 5.
    Miyazaki Y, Mahankali A, Matsuda M, et al. Improved glycemic control and enhanced insulin sensitivity in type 2 diabetic subjects treated with pioglitazone. Diabetes Care 2001; 24(4): 710–9PubMedCrossRefGoogle Scholar
  6. 6.
    Miyazaki Y, Glass L, Triplitt C, et al. Effect of rosiglitazone on glucose and non-esterified fatty acid metabolism in type II diabetic patients. Diabetologia 2001; 44(12): 2210–9PubMedCrossRefGoogle Scholar
  7. 7.
    Reaven GA. Banting Lecture 1988: Role of insulin resistance in human disease. Diabetes 1988; 37(12): 1595–607PubMedCrossRefGoogle Scholar
  8. 8.
    Giusti V, Verdumo C, Suter M, et al. Expression of peroxisome proliferator-activated receptor-γ1 and peroxisome proliferator-activated receptor-γ2 in visceral and subcutaneous adipose tissue of obese women. Diabetes 2003; 52(7): 1673–6PubMedCrossRefGoogle Scholar
  9. 9.
    The DREAM (Diabetes REduction Assessment with ramipril and rosiglitazone Medication) Trial Investigators. Effect of rosiglitazone on the frequency of diabetes in patients with impaired glucose tolerance or impaired fasting glucose: a randomised controlled trial. Lancet 2006 Sept 23; 368(9541): 1096–105CrossRefGoogle Scholar
  10. 10.
    Kahn SE, Haffner SM, Heise MA, et al. Glycemic durability of rosiglitazone, metformin, or glyburide monotherapy. N Engl J Med 2006 Dec 7; 355(23): 2427–43PubMedCrossRefGoogle Scholar
  11. 11.
    Nakamura T, Ushiyama C, Osada S, et al. Pioglitazone reduces urinary podocyte excretion in type 2 diabetes patients with microalbuminuria. Metabolism 2001; 50(10): 1193–6PubMedCrossRefGoogle Scholar
  12. 12.
    Bakris G, Viberti G, Weston WM, et al. Rosiglitazone reduces urinary albumin excretion in type II diabetes. J Hum Hypertens 2003; 17: 7–12PubMedCrossRefGoogle Scholar
  13. 13.
    Natali A, Baldeweg S, Toschi E, et al. Vascular effects of improving metabolic control with metformin or rosiglitazone in type 2 diabetes. Diabetes Care 2004; 27(6): 1349–57PubMedCrossRefGoogle Scholar
  14. 14.
    Langenfeld MR, Forst T, Hohberg C, et al. Pioglitazone decreases carotid intima-media thickness independently of glycemic control in patients with type 2 diabetes mellitus: results from a controlled randomized study. Circulation 2005 May 17; 111(19): 2525–31PubMedCrossRefGoogle Scholar
  15. 15.
    Satoh N, Ogawa Y, Usui T, et al. Antiatherogenic effect of pioglitazone in type 2 diabetic patients irrespective of the responsiveness to its antidiabetic effect. Diabetes Care 2003; 26(9): 2493–9PubMedCrossRefGoogle Scholar
  16. 16.
    Marfella R, D’Amico M, Esposito K, et al. The ubiquitin-proteasome system and inflammatory activity in diabetic atherosclerotic plaques: effects of rosiglitazone treatment. Diabetes 2006; 55(3): 622–32PubMedCrossRefGoogle Scholar
  17. 17.
    Dormandy JA, Charbonnel B, Eckland DJA, et al. Secondary prevention of macrovascular events in patients with type 2 diabetes in the PROactive Study (PROspective pioglitAzone Clinical Trial in macro Vascular Events): a randomised controlled trial. Lancet 2005 Oct 8; 366(9493): 1279–89PubMedCrossRefGoogle Scholar
  18. 18.
    Sauer WH, Cappola AR, Berlin JA, et al. Insulin sensitizing pharmacotherapy for prevention of myocardial infarction in patients with diabetes mellitus. Am J Cardiol 2006; 97(5): 651–4PubMedCrossRefGoogle Scholar
  19. 19.
    Wilcox R, Bousser M-G, Betteridge DJ, et al. Effects of pioglitazone in patients with type 2 diabetes with or without previous stroke: results from PROactive (PROspective pioglitAzone Clinical Trial in macroVascular Events 04). Stroke 2007; 38(3): 865–73PubMedCrossRefGoogle Scholar
  20. 20.
    Schwartz AV, Sellmeyer DE, Vittinghoff E, et al. Thiazolidinedione use and bone loss in older diabetic adults. J Clin Endocrinol Metab 2006; 91(9): 3349–54PubMedCrossRefGoogle Scholar
  21. 21.
    Adams M, Montague CT, Prins JB, et al. Activators of peroxisome proliferator-activated receptor γ have depot-specific effects on human preadipocyte differentiation. J Clin Invest 1997; 100(12): 3149–53PubMedCrossRefGoogle Scholar
  22. 22.
    Miyazaki Y, Mahankali A, Matsuda M, et al. Effect of pioglitazone on abdominal fat distribution and insulin sensitivity in type 2 diabetic patients. J Clin Endocrinol Metab 2002; 87(6): 2784–91PubMedCrossRefGoogle Scholar
  23. 23.
    Kolak M, Yki-Jarvinen H, Kannisto K, et al. Effects of chronic rosiglitazone therapy on gene expression in human adipose tissue in vivo in patients with type 2 diabetes. J Clin Endocrinol Metab 2007; 92(2): 720–4PubMedCrossRefGoogle Scholar
  24. 24.
    Nichols GA, Hillier TA, Erbey JR, et al. Congestive heart failure in type 2 diabetes. Diabetes Care 2001; 24(9): 1614–9 752PubMedCrossRefGoogle Scholar
  25. 25.
    Kenchaiah S, Evans JC, Levy D, et al. Obesity and the risk of heart failure. N Engl J Med 2002 Aug 1; 347(5): 305–13PubMedCrossRefGoogle Scholar
  26. 26.
    Li X, Li S, Ulusoy E, et al. Childhood adiposity as a predictor of cardiac mass in adulthood: the Bogalusa Heart Study. Circulation 2004 Nov 30; 110(922): 3488–92PubMedCrossRefGoogle Scholar
  27. 27.
    Chinali M, de Simone G, Roman MJ, et al. Impact of obesity on cardiac geometry and function in a population of adolescents: the Strong Heart Study. J Am Coll Cardiol 2006 Jun 6; 47(11): 2267–73PubMedCrossRefGoogle Scholar
  28. 28.
    Arnlov J, Lind L, Zethelius B, et al. Several factors associated with the insulin resistance syndrome are predictors of left ventricular systolic dysfunction in a male population after 20 years of follow-up. Am Heart J 2001; 142(4): 720–4PubMedCrossRefGoogle Scholar
  29. 29.
    Ingelsson E, Sundstrom J, Arnlov J, et al. Insulin resistance and risk of congestive heart failure. JAMA 2005 Jul 20; 294(3): 334–41PubMedCrossRefGoogle Scholar
  30. 30.
    Swan JW, Anker SD, Walton C, et al. Insulin resistance in chronic heart failure: relation to severity and etiology of heart failure. J Am Coll Cardiol 1997; 30(2): 527–32PubMedCrossRefGoogle Scholar
  31. 31.
    Doehner W, Rauchhaus M, Ponikowski P, et al. Impaired insulin sensitivity as an independent risk factor for mortality in patients with stable chronic heart failure. J Am Coll Cardiol 2005 Sep 20; 46(6): 1019–26PubMedCrossRefGoogle Scholar
  32. 32.
    Kannel WB, Hjortland M, Castelli WP. Role of diabetes in congestive heart failure: the Framingham Study. Am J Cardiol 1974 Jul; 34(1): 29–34PubMedCrossRefGoogle Scholar
  33. 33.
    Iribarren C, Karter AJ, Go AS, et al. Glycemic control and heart failure among adult patients with diabetes. Circulation 2001 Jun 5; 103(22): 2668–73PubMedCrossRefGoogle Scholar
  34. 34.
    SmithKline Beecham Pharmaceuticals. Avandia (rosiglitazone) [package insert]. Philadelphia (PA): SmithKline Beecham Pharmaceuticals, 2001Google Scholar
  35. 35.
    Takeda Pharmaceuticals, Inc. Actos (pioglitazone) [package insert]. Lincolnshire (IL): Takeda Pharmaceuticals, Inc., 2000Google Scholar
  36. 36.
    Rennings AJM, Smits P, Stewart MW, et al. Fluid retention and vascular effects of rosiglitazone in obese, insulin-resistant, nondiabetic subjects. Diabetes Care 2006; 29(3): 581–7PubMedCrossRefGoogle Scholar
  37. 37.
    Basu A, Jensen MD, McCann F, et al. Effects of pioglitazone versus glipizide on body fat distribution, body water content, and hemodynamics in type 2 diabetes. Diabetes Care 2006; 29(3): 510–4PubMedCrossRefGoogle Scholar
  38. 38.
    Karalliedde J, Buckingham R, Starkie M, et al. Effect of various diuretic treatments on rosiglitazone-induced fluid retention. J Am Soc Nephrol 2006; 17(12): 3482–90PubMedCrossRefGoogle Scholar
  39. 39.
    Nagasawa E, Abe Y, Nishimura J, et al. Pivotal role of peroxisome proliferator-activated receptor γ (PPARγ) in regulation of erythroid progenitor cell proliferation and differentiation. Exp Hematol 2005; 33(8): 857–64PubMedCrossRefGoogle Scholar
  40. 40.
    Raji A, Seely EW, Bekins SA, et al. Rosiglitazone improves insulin sensitivity and lowers blood pressure in hypertensive patients. Diabetes Care 2003; 26(1): 172–8PubMedCrossRefGoogle Scholar
  41. 41.
    Gerber P, Lubben G, Heusler S, et al. Effects of pioglitazone on metabolic control and blood pressure: a randomised study in patients with type 2 diabetes mellitus. Curr Med Res Opin 2003; 19(6): 532–9PubMedCrossRefGoogle Scholar
  42. 42.
    Zanchi A, Chiolero A, Maillard M, et al. Effects of the peroxisomal proliferator-activated receptor-γ agonist pioglitazone on renal and hormonal responses to salt in healthy men. J Clin Endocrinol Metab 2004; 89(3): 1140–5PubMedCrossRefGoogle Scholar
  43. 43.
    Guan Y, Hao C, Cha DR, et al. Thiazolidinediones expand body fluid volume through PPARγ stimulation of ENaC-mediated renal salt absorption. Nat Med 2005; 11(8): 861–6PubMedCrossRefGoogle Scholar
  44. 44.
    Zhang H, Zhang A, Kohan DE, et al. Collecting duct-specific deletion of peroxisome proliferator-activated receptor γ blocks thiazolidinedione-induced fluid retention. Proc Natl Acad Sci 2005 Jun 28; 102(26): 9406–11PubMedCrossRefGoogle Scholar
  45. 45.
    Kleyman TR, Cragoe EJ. Amiloride and its analogs as tools in the study of ion transport. J Membrane Biol 1988; 105(1): 1–21CrossRefGoogle Scholar
  46. 46.
    Hong G, Lockhart A, Davis B, et al. PPARγ activation enhances cell surface ENaCα via up-regulation of SGK1 in human collecting duct cells. FASEB J 2003; 17(13): 1966–8PubMedGoogle Scholar
  47. 47.
    Kalambokis GN, Tsatsoulis AA, Tsianos EV. The edematogenic properties of insulin. Am J Kidney Dis 2004; 44(4): 575–90PubMedGoogle Scholar
  48. 48.
    Raji A, Gerhard-Herman MD, Williams JS, et al. Effect of pioglitazone on insulin sensitivity, vascular function and cardiovascular inflammatory markers in insulin-resistant non-diabetic Asian Indians. Diabet Med 2006; 23(5): 537–43PubMedCrossRefGoogle Scholar
  49. 49.
    Wang J, Barbry P, Maiyar AC, et al. SGK integrates insulin and mineralocorticoid regulation of epithelial sodium transport. Am J Physiol Renal Physiol 2001; 280(2): F303–13PubMedGoogle Scholar
  50. 50.
    Nofziger C, Chen L, Shane MA, et al. PPARγ agonists do not directly enhance basal or insulin-stimulated Na+ transport via the epithelial Na+ channel. Pflugers Arch 2005; 451(3): 445–53PubMedCrossRefGoogle Scholar
  51. 51.
    Raskin P, Rendell M, Riddle MC, et al. A randomized trial of rosiglitazone therapy in patients with inadequately controlled insulin-treated type 2 diabetes. Diabetes Care 2001; 24(7): 1226–32PubMedCrossRefGoogle Scholar
  52. 52.
    Rosenstock J, Einhorn D, Hershon K, et al. Efficacy and safety of pioglitazone in type 2 diabetes: a randomised, placebo-controlled study in patients receiving stable insulin therapy. Int J Clin Pract 2002; 56(4): 251–7PubMedGoogle Scholar
  53. 53.
    Niemeyer NV, Janney LM. Thiazolidinedione-induced edema. Pharmacotherapy 2002; 22(7): 924–9PubMedCrossRefGoogle Scholar
  54. 54.
    Tang WHW, Francis GS, Hoogwerf BJ, et al. Fluid retention after initiation of thiazolidinedione therapy in diabetic patients with established chronic heart failure. J Am Coll Cardiol 2003 Apr 16; 41(8): 1394–8PubMedCrossRefGoogle Scholar
  55. 55.
    Yamakawa K, Hosoi M, Koyama H, et al. Peroxisome proliferator-activated receptor-γ agonists increase vascular endothelial growth factor expression in human vascular smooth muscle cells. Biochem Biophys Res Comm 2000 May 19; 271(3): 571–4PubMedCrossRefGoogle Scholar
  56. 56.
    Emoto M, Fukuda N, Nakamori Y, et al. Plasma concentrations of vascular endothelial growth factor are associated with peripheral oedema in patients treated with thiazolidinedione. Diabetologia 2006; 49(9): 2217–8PubMedCrossRefGoogle Scholar
  57. 57.
    Sotiropoulos KB, Clermont A, Yasuda Y, et al. Adipose-specific effect of rosiglitazone on vascular permeability and protein kinase C activation: novel mechanism for PPARγ agonist’s effects on edema and weight gain. FASEB J 2006; 20(6): E367–80Google Scholar
  58. 58.
    Coluciello M. Vision loss due to macular edema induced by rosiglitazone treatment of diabetes mellitus. Arch Ophthalmol 2003; 123(9): 1273–5CrossRefGoogle Scholar
  59. 59.
    Ryan EH, Han DP, Ramsay RC, et al. Diabetic macular edema associated with glitazone use. Retina 2006; 26(5): 562–70PubMedCrossRefGoogle Scholar
  60. 60.
    Delea TE, Edelsberg JS, Hagiwara M. Use of thiazolidinediones and risk of heart failure in people with type 2 diabetes: a retrospective cohort study. Diabetes Care 2003; 26(11): 2983–9PubMedCrossRefGoogle Scholar
  61. 61.
    Karter AJ, Ahmed AT, Liu J, et al. Pioglitazone initiation and subsequent hospitalization for congestive heart failure. Diabet Med 2005; 22(8): 986–93 753PubMedCrossRefGoogle Scholar
  62. 62.
    Rajagopalan R, Rosenson RS, Fernandes AW, et al. Association between congestive heart failure and hospitalization in patients with type 2 diabetes mellitus receiving treatment with insulin or pioglitazone: a retrospective data analysis. Clin Ther 2004; 26(9): 1400–10PubMedCrossRefGoogle Scholar
  63. 63.
    Kermani A, Garg A. Thiazolidinedione-associated congestive heart failure and pulmonary edema. Mayo Clin Proc 2003; 78(9): 1088–91PubMedCrossRefGoogle Scholar
  64. 64.
    Srivastava PM, Calafiore P, MacIsaac RJ, et al. Thiazolidinediones and congestive heart failure-exacerbation or new onset of left ventricular dysfunction? Diabet Med 2004; 21(8): 945–50PubMedCrossRefGoogle Scholar
  65. 65.
    St John-Sutton M, Rendell M, Dandona P, et al. A comparison of the effects of rosiglitazone and glyburide on cardiovascular function and glycemic control in patients with type 2 diabetes. Diabetes Care 2002; 25(11): 2058–64CrossRefGoogle Scholar
  66. 66.
    Masoudi FA, Inzucchi SE, Wang Y, et al. Thiazolidinediones, metformin, and outcomes in older patients with diabetes and heart failure: an observational study. Circulation 2005; 111(5): 583–90PubMedCrossRefGoogle Scholar
  67. 67.
    Inzucchi SE, Masoudi FA, Wang Y, et al. Insulin-sensitizing antihyperglycemic drugs and mortality after acute myocardial infarction. Diabetes Care 2005; 28(7): 1680–9PubMedCrossRefGoogle Scholar
  68. 68.
    Buckingham RE, Hanna A. Thiazolidinedione insulin sensitizers and the heart: a tale of two organs? Diabetes Obes Metab (OnlineEarly Articles). Epub 2007 Jan 16Google Scholar
  69. 69.
    Reynolds LR, Konz EC, Frederich RC, et al. Rosiglitazone amplifies the benefits of lifestyle intervention measures in long-standing type 2 diabetes mellitus. Diabetes Obes Metab 2002; 4(4): 270–5PubMedCrossRefGoogle Scholar
  70. 70.
    Asnani S, Richard BC, Desouza C, et al. Is weight loss possible in patients treated with thiazolidindiones? Experience with a low-calorie diet. Curr Med Res Opin 2003; 19(7): 609–13PubMedCrossRefGoogle Scholar
  71. 71.
    Nesto RW, Bell D, Bonow RO, et al. Thiazolidinedione use, fluid retention, and congestive heart failure: a consensus statement from the American Heart Association and American Diabetes Association. Circulation 2003 Dec 9; 108(23): 2941–8PubMedCrossRefGoogle Scholar
  72. 72.
    Iwanaga Y, Nishi I, Furuichi S, et al. B-Type natriuretic peptide strongly reflects diastolic wall stress in patients with chronic heart failure. J Am Coll Cardiol 2006; 47(4): 742–8PubMedCrossRefGoogle Scholar
  73. 73.
    Bhalla MA, Chiang A, Epshteyn VA, et al. Prognostic role of B-type natriuretic peptide levels in patients with type 2 diabetes mellitus. J Am Coll Cardiol 2004; 44(5): 1047–52PubMedCrossRefGoogle Scholar
  74. 74.
    Wang TJ, Larson MG, Levy D, et al. Impact of obesity on plasma natriuretic peptide levels. Circulation 2004 Feb 10; 109(5): 594–600PubMedCrossRefGoogle Scholar
  75. 75.
    Horwich TB, Hamilton MA, Fonarow GC. B-Type natriuretic peptide levels in obese patients with advanced heart failure. J Am Coll Cardiol 2006; 47(1): 85–90PubMedCrossRefGoogle Scholar
  76. 76.
    Tsutamoto T, Wada A, Sakai H, et al. Relationship between renal function and plasma brain natriuretic peptide in patients with heart failure. J Am Coll Cardiol 2006; 47(3): 582–6PubMedCrossRefGoogle Scholar
  77. 77.
    Ogawa S, Takeuchi K, Ito S. Plasma BNP levels in the treatment of type 2 diabetes with pioglitazone. J Clin Endocrinol Metab 2003; 88(8): 3993–6PubMedCrossRefGoogle Scholar
  78. 78.
    Dargie H, Hildebrandt PR, Riegger G, et al. Baseline B-type natriuretic peptide identifies patients with type 2 diabetes and class I/II heart failure at risk of fluid retention when treated with rosiglitazone [abstract no. 1048-173]. J Am Coll Cardiol 2005 Feb 1; 45 (3 Suppl. A): 139AGoogle Scholar
  79. 79.
    Hansen L, Ekstrom CT, Palacios RT, et al. The Pro12Ala variant of the PPARG gene is a risk factor for peroxisome proliferator-activated receptor-γ/α agonist-induced edema in type 2 diabetic patients. J Clin Endocrinol Metab 2006; 91(9): 3446–50PubMedCrossRefGoogle Scholar
  80. 80.
    Gregersen MI. Blood volume. Physiol Rev 1958; 39: 307–42Google Scholar
  81. 81.
    Dill DB, Costill DL. Calculation of percentage changes in volumes of blood, plasma, and red cells in dehydration. J Appl Physiol 1974; 37: 247–8PubMedGoogle Scholar
  82. 82.
    Wilson DR, Honrath U, Sonnenberg H. Thiazide diuretic effect on medullary collecting duct function in the rat. Kidney Int 1983; 23: 711–6PubMedCrossRefGoogle Scholar
  83. 83.
    Kim G-H, Masilamani S, Turner R, et al. The thiazide-sensitive Na-Cl cotransporter is an aldosterone-induced protein. Proc Natl Acad Sci U S A 1998; 95(11): 14552–7PubMedCrossRefGoogle Scholar
  84. 84.
    Shankar SS, Brater DC. Loop diuretics: from the Na-K-2Cl transporter to clinical use. Am J Physiol Renal Physiol 2003; 284(1): F11–21PubMedGoogle Scholar
  85. 85.
    Boden G, Homko C, Mozzoli M, et al. Combined use of rosiglitazone and fenofibrate in patients with type 2 diabetes: prevention of fluid retention. Diabetes 2007; 56: 248–55PubMedCrossRefGoogle Scholar
  86. 86.
    Karalliedde J, Viberti GC. Comment on: Boden et al. (2007) Combined use of rosiglitazone and fenofibrate in patients with type 2 diabetes: prevention of fluid retention: Diabetes 56: 248–255 [letter]. Diabetes 2007 May; 56 (5): e3CrossRefGoogle Scholar
  87. 87.
    Nissen SE, Wolski K, Topol EJ. Effect of murgalitazar on death and major adverse cardiovascular events in patients with type 2 diabetes mellitus. JAMA 2005; 294: 2581–6PubMedCrossRefGoogle Scholar

Copyright information

© Adis Data Information BV 2007

Authors and Affiliations

  1. 1.Unit for Metabolic Medicine, Department of Diabetes and Endocrinology, Cardiovascular DivisionKing’s College London School of Medicine, Guy’s Hospital, King’s College LondonLondonUK

Personalised recommendations