Clinical Drug Investigation

, Volume 24, Issue 4, pp 217–225 | Cite as

Regression of Microalbuminuria in Type 2 Diabetics after Switch to Irbesartan Treatment

An Observational Study in 38 016 Patients in Primary Care
Original Research Article


Objective: This study aimed to assess the blood pressure-lowering potency, renoprotective efficacy and safety of the angiotensin II type 1 (AT1)-receptor blocker irbesartan in monotherapy or in combination with hydrochlorothiazide or other antihypertensive medications in patients with type 2 diabetes mellitus switched from various antihypertensive pretreatments.

Design and methods: Multicentre, open, prospective, 6-month observational study in 38 016 patients at 9838 general practitioners’ offices throughout Germany. Microalbuminuria in type 2 diabetics was measured with semiquantitative immunological Micral-II urine dipstick tests.

Main outcome measure: Proportion of patients with albuminuria at baseline and at 3 and 6 months. Analysis of adverse events.

Results: The study population consisted of an equal number of males and females, mean body mass index was 28.4 kg/m2, and mean glycosylated haemoglobin (HbA1c) was 7.2%. After the switch to irbesartan (in 86% of patients to the 300mg dosage in mono-or combination therapy), mean systolic/diastolic blood pressure was decreased by 23/12mm Hg. Irbesartan treatment over 6 months reduced the proportion of patients with microalbuminuria from 49.2 to 23.2% (relative reduction: 52.8%; p < 0.05) and the rate of patients with macroalbuminuria from 6.0 to 4.4% (relative reduction: 26.7%; p < 0.05). The renoprotective effect of irbesartan was consistent in various subgroups (analyses by sex, weight, diabetes duration, insulin treatment, strength of blood pressure-lowering effect, and antihypertensive pretreatment). Tolerability was excellent: 99.6% of patients remained free of any adverse events during the study.

Conclusion: The profound blood pressure-lowering and renoprotective effect of irbesartan in type 2 diabetes documented in clinical endpoint studies was confirmed in second-line therapy in a large sample of primary-care patients. Furthermore, in patients switched from previous ACE-inhibitor therapy, the renoprotective effect of irbesartan was of the same magnitude as in the total cohort.


Irbesartan HCTZ Renoprotective Effect Oral Antidiabetic Drug Irbesartan Treatment 
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.



This study was supported by Sanofi-Synthelabo Berlin, Germany. We thank the investigators for their commitment to the study. The statistical analysis was performed by Dr Schauerte GmbH, Munich, Germany. PB is also an employee of Sanofi-Synthelabo Germany. The other authors have reported no conflicts of interest directly relevant to the content of this study.


  1. 1.
    Stamler J, Vaccaro O, Neaton JD, et al. Diabetes, other risk factors, and 12-yr cardiovascular mortality for men screened in the multiple risk factor intervention trial. Diabetes Care 1993; 16: 434–44PubMedCrossRefGoogle Scholar
  2. 2.
    Haffner SM, Lehto S, Ronnemaa T, et al. Mortality from coronary heart disease in subjects with type 2 diabetes and in nondiabetic subjects with and without prior myocardial infarction. N Engl J Med 1998; 339: 229–34PubMedCrossRefGoogle Scholar
  3. 3.
    Ritz E. Albuminuria and vascular damage: the vicious twins. N Engl J Med 2003; 348: 2349–52PubMedCrossRefGoogle Scholar
  4. 4.
    American Diabetes Association. Diabetic nephropathy. Diabetes Care 2002; 25: 85–9CrossRefGoogle Scholar
  5. 5.
    Hillege H, Janssen W, Bak A, et al. Microalbuminuria is common, also in a nondiabetic, nonhypertensive population, and an independent indicator of cardiovascular risk factors and cardiovascular morbidity. J Intern Med 2001; 249: 519–26PubMedCrossRefGoogle Scholar
  6. 6.
    Gerstein HC, Mann JFE, Yi Q, et al. Albuminuria and risk of cardiovascular events, death, and heart failure in diabetic and nondiabetic individuals. JAMA 2001; 286: 421–6PubMedCrossRefGoogle Scholar
  7. 7.
    Stehouwer C, Nauta J, Zeldenrust G, et al. Urinary albumin excretion, cardiovascular disease, and endothelial dysfunction in non-insulin-dependent diabetes mellitus. Lancet 1992; 340: 319–23PubMedCrossRefGoogle Scholar
  8. 8.
    Beatty O, Ritchie C, Bell P, et al. Microalbuminuria as identified by a spot morning urine specimen in non-insulin-treated diabetes: an eight-year follow-up study. Diabet Med 1995; 12: 261–6PubMedCrossRefGoogle Scholar
  9. 9.
    Damsgaard E, Froland A, Jorgensen O, et al. Prognostic value of urinary albumin excretion rate and other risk factors in elderly diabetic patients and non-diabetic control subjects surviving the first 5 years after assessment. Diabetologia 1993; 36: 1030–6PubMedCrossRefGoogle Scholar
  10. 10.
    MacLeod J, Lutale J, Marshall S. Albumin excretion and vascular deaths in NIDDM. Diabetologia 1995; 38: 610–6PubMedCrossRefGoogle Scholar
  11. 11.
    American Diabetes Association. Position statement on “diabetic nephropathy”: position statement. Diabetes Care 2004; 27Suppl. 1: S79–83Google Scholar
  12. 12.
    Hasslacher C. Diabetische Nephropathie in “Praxis-Leitlinien der Deutschen Diabetes Gesellschaft”. Diabetes und Stoffwechsel 2002; 11 Suppl. 2: 17–9Google Scholar
  13. 13.
    Parving HH, Lehnert H, Brochner-Mortensen J, et al. The effect of irbesartan on the development of diabetic nephropathy in patients with type 2 diabetes. N Engl J Med 2001; 345: 870–8PubMedCrossRefGoogle Scholar
  14. 14.
    Lewis EJ, Hunsicker LG, Clarke WR, et al. Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes. N Engl J Med 2001; 345: 851–60PubMedCrossRefGoogle Scholar
  15. 15.
    Brenner BM, Cooper ME, de Zeeuw D, et al. Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. N Engl J Med 2001; 345: 861–9PubMedCrossRefGoogle Scholar
  16. 16.
    Fernandez I, Paez Pinto J, Hermosin Bono T, et al. Rapid screening test evaluation for microalbuminuria in diabetes mellitus. Acta Diabetol 1998; 35: 199–202CrossRefGoogle Scholar
  17. 17.
    Piehlmeier W, Renner R, Schramm W, et al. Screening of diabetic patients for microalbuminuria in primary care: The PROSIT-Project. Proteinuria Screening and Intervention. Exp Clin Endocrinol Diabetes 1999; 107: 244–51PubMedGoogle Scholar
  18. 18.
    SAS. Cary NC: SAS Institute Inc., 1999Google Scholar
  19. 19.
    Guidelines committee. European Society of Hypertension-European Society of Cardiology guidelines for the management of arterial hypertension. J Hypertens 2003; 21: 1011–53CrossRefGoogle Scholar
  20. 20.
    Chobanian AV, Bakris GL, Black HR, et al. The seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: The JNC 7 Report. JAMA 2003; 289: 2560–72PubMedCrossRefGoogle Scholar
  21. 21.
    Brueckel J, Koebberling J. Definition, Klassifikation und Diagnostik des Diabetes mellitus. In “Praxis-Leitlinien der Deutschen Diabetes Gesellschaft” Diabetes und Stoffwechsel 2002; 11Suppl. 2: 6–8Google Scholar
  22. 22.
    Zelmanovitz T, Gross J, Oliveira J, et al. The receiver operating characteristics curve in the evaluation of a random urine specimen as a screening test for diabetic nephropathy. Diabetes Care 1997; 20: 516–9PubMedCrossRefGoogle Scholar
  23. 23.
    Lum G. How effective are screening tests for microalbuminuria in random urine specimens? Ann Clin Lab Sci 2000; 30: 406–11PubMedGoogle Scholar
  24. 24.
    Vestbo E, Damsgaard E, Froland A, et al. Urinary albumin excretion in a population based cohort. Diabet Med 1995; 12: 488–93PubMedCrossRefGoogle Scholar
  25. 25.
    Concato J, Shah N, Horwitz RI. Randomized, controlled trials, observational studies, and the hierarchy of research designs. N Engl J Med 2000; 342: 1887–92PubMedCrossRefGoogle Scholar
  26. 26.
    Lewis EJ, Hunsicker LG, Bain RP, et al. The effect of angiotensin-converting-enzyme inhibition on diabetic nephropathy. N Engl J Med 1993; 329: 1456–62PubMedCrossRefGoogle Scholar
  27. 27.
    ACE Inhibitors in Diabetic Nephropathy Trialist Group. Should all patients with type 1 diabetes mellitus and microalbuminuria receive angiotensin-converting enzyme inhibitors? A meta-analysis of individual patient data. Ann Intern Med 2001; 134: 370–9Google Scholar
  28. 28.
    Taal M, Brenner B. Renoprotective benefits of RAS inhibition: from ACEI to angiotensin II antagonists. Kidney Int 2000; 57: 1803–17PubMedCrossRefGoogle Scholar
  29. 29.
    Law MR, Wald NJ, Morris JK, et al. Value of low dose combination treatment with blood pressure lowering drugs: analysis of 354 randomised trials. BMJ 2003; 326: 1427–31PubMedCrossRefGoogle Scholar
  30. 30.
    The ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group. Major outcomes in high-risk hypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker vs diuretic: the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). JAMA 2002; 288: 2981–97CrossRefGoogle Scholar
  31. 31.
    Myers MG. Compliance in hypertension: why don’t patients take their pills? CMAJ 1999; 160: 64–5PubMedGoogle Scholar
  32. 32.
    Hasford J, Mimran A, Simons W. A population-based European cohort study of persistence in newly diagnosed hypertensive patients. J Hum Hypertens 2002; 16: 569–75PubMedCrossRefGoogle Scholar
  33. 33.
    Bakris GL, Weir MR, Shanifar S, et al. Effects of blood pressure level on progression of diabetic nephropathy: results from the RENAAL study. Arch Intern Med 2003; 163: 1555–65PubMedCrossRefGoogle Scholar
  34. 34.
    UK Prospective Diabetes Study Group. Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 38. BMJ 1998; 317: 703–13CrossRefGoogle Scholar
  35. 35.
    Guidelines Committee. European Society of Hypertension-European Society of Cardiology guidelines for the management of arterial hypertension. J Hypertens 2003; 21: 1011–53CrossRefGoogle Scholar
  36. 36.
    Hansson L, Zanchetti A, Carruthers S, et al. Effects of intensive blood-pressure lowering and low-dose aspirin in patients with hypertension: principal results of the Hypertension Optimal Treatment (HOT) randomised trial. HOT Study Group. Lancet 1998; 351: 1755–62PubMedCrossRefGoogle Scholar
  37. 37.
    Schulte K, Fischer M, Meyer-Sabellak W. Efficacy and toler-ability of candesartan cilexetil monotherapy or in combination with other antihypertensive drugs: results of the AURA study. Clin Drug Invest 1999; 18: 453–60CrossRefGoogle Scholar
  38. 38.
    Scholze J, Probst G, Bertsch K. Valsartan alone and in combination with hydrochlorothiazide in general practice: results from two postmarketing surveillance studies involving 54 928 patients with essential hypertension. Clin Drug Invest 2000; 20: 1–7CrossRefGoogle Scholar
  39. 39.
    Bramlage P, Wittchen H, Pittrow D, et al. Mikroalbuminurie als früher Marker für eine erhöhte Morbidität und Mortalität. Fortschr Med Orig 2003; 121Suppl. I: 28–32PubMedGoogle Scholar

Copyright information

© Adis Data Information BV 2004

Authors and Affiliations

  1. 1.Department of Endocrinology and MetabolismUniversity of MagdeburgMagedeburgGermany
  2. 2.Institute of Clinical Pharmacology Medical FacultyTechnical UniversityDresdenGermany

Personalised recommendations