Clinical Drug Investigation

, Volume 13, Supplement 1, pp 42–49 | Cite as

Effects of Amlodipine vs Enalapril on Microalbuminuria in Hypertensive Patients with Type II Diabetes

  • Roberto Fogari
  • A. Zoppi
  • G. D. Malamani
  • P. Lusardi
  • M. Destro
  • L. Corradi
Section 1: Pharmacodynamic Profile


The effects of once-daily amlodipine 10mg or enalapril 20mg on urinary albumin excretion (UAE) were evaluated over 12 months, in a randomised trial of 50 hypertensive patients with type II (non-insulin-dependent) diabetes mellitus and microalbuminuria. Both drugs significantly reduced systolic and diastolic blood pressure without affecting heart rate or glucose homeostasis. UAE was significantly reduced after 3 months of treatment with enalapril, and 6 months of therapy with amlodipine. The percentage reduction in UAE significantly correlated with the decrement in systolic blood pressure and duration of hypertension in both treatment groups. Creatinine clearance was unaffected by enalapril, but was significantly increased by amlodipine. Long term treatment with either amlodipine or enalapril was therefore effective in reducing UAE in hypertensive patients with type II diabetes and microalbuminuria.


Diabetic Nephropathy Angiotensin Converting Enzyme Enalapril Calcium Antagonist Amlodipine 
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.


  1. 1.
    Viberti GC, Hill RD, Jarret RJ, et al. Microalbuminuria as a predictor of clinical nephropathy in insulin dependent diabetes mellitus. Lancet 1982; 1: 1430–2PubMedCrossRefGoogle Scholar
  2. 2.
    Parving HH, Oxenboll B, Svendsen PA, et al. Early detection of patients at risk of developing diabetic nephropathy: a longitudinal study of urinary albumin excretion. Acta Endocrinol 1982; 100: 550–5PubMedGoogle Scholar
  3. 3.
    Mogensen CE. Microalbuminuria predicts clinical proteinuria and early mortality in maturity-onset diabetes. N Engl J Med 1984; 310: 356–60PubMedCrossRefGoogle Scholar
  4. 4.
    Tuttle KR, Stein JH, De Fronzo RA. The natural history of diabetic nephropathy. Semin Nephrol 1990; 10: 184–93PubMedGoogle Scholar
  5. 5.
    Ritz E. Hypertension in diabetic nephropathy: prevention and treatment. Am Heart J 1993; 125: 1514–9PubMedCrossRefGoogle Scholar
  6. 6.
    Jarret RJ, Viberti GC, Argyropoulos A, et al. Microalbuminuria predicts mortality in non-insulin-dependent diabetes. Diab Med 1984; 1: 17–9CrossRefGoogle Scholar
  7. 7.
    Schmitz A, Vaeth M. Microalbuminuria: a major risk factor in non-insulin-dependent diabetes. A 10-year follow-up study of 503 patients. Diab Med 1988; 5: 126–34CrossRefGoogle Scholar
  8. 8.
    Mattock MB, Keen H, Viberti G, et al. Coronary heart disease and urinary albumin excretion rate in type 2 (non-insulin-dependent) diabetic patients. Diabetologia 1988; 31: 82–7PubMedCrossRefGoogle Scholar
  9. 9.
    Viberti GC. Etiology and prognostic significance of microalbuminuria in diabetes. Diabetes Care 1988; 11: 840–5PubMedCrossRefGoogle Scholar
  10. 10.
    Allawi J, Jarret RJ. Microalbuminuria and cardiovascular risk factors in type II diabetes mellitus. Diabetic Med 1990; 7: 115–8PubMedCrossRefGoogle Scholar
  11. 11.
    Epstein M, Sowers JR. Diabetes mellitus and hypertension. Hypertension 1992; 19: 402–18CrossRefGoogle Scholar
  12. 12.
    Mogensen CE. Long-term antihypertensive treatment inhibiting progression of diabetic nephropathy. BMJ 1982; 285: 685–8PubMedCrossRefGoogle Scholar
  13. 13.
    Parving HH, Andersen AR, Smidt U, et al. Effects of antihypertensive treatment on kidney function in diabetic nephropathy. BMJ 1987; 294: 1443–7PubMedCrossRefGoogle Scholar
  14. 14.
    Fuller JH, Head J, and the WHO Multinational Study Group. Blood pressure, proteinuria and their relationship with circulatory mortality: the WHO multinational study of vascular disease in diabetics. Diab Metab 1989; 15: 273–7Google Scholar
  15. 15.
    Mathiesen E, Ronn B, Jensen T, et al. Relationship between blood pressure and urinary albumin excretion in development of microalbuminuria. Diabetes 1990; 39: 245–9PubMedCrossRefGoogle Scholar
  16. 16.
    Ribstein J, Mimran A. Blood pressure reduction as a preventive treatment of diabetic nephropathy. Clin Invest Med 1991; 14: 661–70PubMedGoogle Scholar
  17. 17.
    Zatz R, Dunn BR, Meyer TW, et al. Prevention of diabetic glomerulopathy by pharmacological amelioration of glomerular capillary hypertension. J Clin Invest 1986; 77: 1925–30PubMedCrossRefGoogle Scholar
  18. 18.
    Myers BD, Meyer TW. Angiotensin converting enzyme inhibitors in the prevention of experimental diabetic glomerulopathy. Am J Kidney Dis 1989; 13: 20–4PubMedGoogle Scholar
  19. 19.
    Reams GP, Bauer JH. Effect of enalapril in subjects with hypertension associated with moderate to severe renal dysfunction. Arch Intern Med 1986; 146: 2145–8PubMedCrossRefGoogle Scholar
  20. 20.
    Heeg JE, De Jong PE, Vander Mem GK, et al. Reduction of proteinuria by ACE inhibition. Kidney Int 1987; 32: 78–83PubMedCrossRefGoogle Scholar
  21. 21.
    Abraham PA, Opsahl JA, Halstenson CE, et al. Efficacy and renal effects of enalapril therapy for hypertensive patients with chronic renal insufficiency. Arch Intern Med 1988; 148: 2358–62PubMedCrossRefGoogle Scholar
  22. 22.
    Heeg JE, De Jong PE, Van Der Hemm GK, et al. Efficacy and variability of the antiproteinuric effect of ACE inhibition by lisinopril. Kidney Int 1989; 36: 272–9PubMedCrossRefGoogle Scholar
  23. 23.
    Keane WF, Anderson S, Aurell M, et al. Angiotensin converting enzyme inhibition and progressive renal insufficiency. Ann Intern Med 1989; 111: 503–16PubMedGoogle Scholar
  24. 24.
    Bianchi S, Bigazzi R, Baldari G, et al. Long-term effects of enalapril and nicardipine on urinary albumin excretion in patients with chronic renal insufficiency: a 1-year follow-up. Am J Nephrol 1991; 11: 131–7PubMedCrossRefGoogle Scholar
  25. 25.
    Taguma Y, Kitamoto Y, Futaki G, et al. Effect of Captopril on heavy proteinuria in systemic diabetics. N Engl J Med 1985; 313: 1617–20PubMedCrossRefGoogle Scholar
  26. 26.
    Hommel E, Parving HH, Mathiesen E, et al. Effect of Captopril on kidney function in insulin-dependent diabetic patients with nephropathy. BMJ 1986; 293: 467–70PubMedCrossRefGoogle Scholar
  27. 27.
    Marre M, Chatellier G, Leblanc H, et al. Prevention of diabetic nephropathy with enalapril in normotensive diabetes with microalbuminuria. BMJ 1988; 297: 1092–5PubMedCrossRefGoogle Scholar
  28. 28.
    Parving HH, Hommel E, Smidt VM. Protection of kidney function and decrease in albuminuria by Captopril in insulin dependent diabetics with nephropathy. BMJ 1988; 297: 1086–91PubMedCrossRefGoogle Scholar
  29. 29.
    Baba T, Murabayashi S, Takabe K. Comparison of the renal effects of angiotensin converting enzyme inhibitor and calcium antagonist in hypertensive type II (non-insulin-dependent) diabetic patients with microalbuminuria: a randomized, controlled trial. Diabetologia 1989; 32: 40–4PubMedGoogle Scholar
  30. 30.
    Stornello M, Valvo EV, Scapellato L. Haemodynamic,renal and humoral effects of the calcium-entry-blocker nicardipine and converting enzyme inhibitor Captopril in hypertensive type II diabetic patients with nephropathy. J Cardiovasc Pharmacol 1989; 14: 851–5PubMedCrossRefGoogle Scholar
  31. 31.
    Holdaas H, Hartmann A, Lien MG, et al. Contrasting effects of lisinopril and nifedipine on albuminuria and tubular transport function in insulin dependent diabetics with nephropathy. J Intern Med 1991; 229: 163–70PubMedCrossRefGoogle Scholar
  32. 32.
    Marre M, Hallab M, Billiard A, et al. Small doses of ramipril to reduce microalbuminuria in diabetic patients with incipient nephropathy independently of blood pressure changes. J Cardiovasc Pharmacol 1991; 18 Suppl. 2: S165–8PubMedGoogle Scholar
  33. 33.
    Mathiesen ER, Hommel E, Giese J, et al. Efficacy of Captopril in postponing nephropathy in normotensive insulin dependent diabetic patients with microalbuminuria. BMJ 1991; 303: 81–7PubMedCrossRefGoogle Scholar
  34. 34.
    Ferder L, Daccordi H, Martello M, et al. Angiotensin converting enzyme inhibitors vs Ca-antagonists in the treatment of diabetic hypertensive patients. Hypertension 1992; 19 Suppl. II: 237–42Google Scholar
  35. 35.
    Stornello M, Valvo E, Scapellato L. Persistent albuminuria in normotensive non-insulin-dependent (type II) diabetic patients: comparative effects of ACE-inhibitors and beta-adrenoceptor blockers. Clin Sci 1992; 82: 19–23PubMedGoogle Scholar
  36. 36.
    Wiegmann TB, Gish Herron K, Chonko AM, et al. Effect of angiotensin converting enzyme inhibition on renal function and albuminuria in normotensive type I diabetic patients. Diabetes 1982; 41: 62–7CrossRefGoogle Scholar
  37. 37.
    Harris DC, Hammond WS, Burke TJ, et al. Verapamil protects against progression of experimental chronic renal failure. Kidney Int 1987; 31: 41–6PubMedCrossRefGoogle Scholar
  38. 38.
    Pelayo JC, Harris DC, Shanley PF, et al. Glomerular haemodynamic adaptation in remnant nephrons: effects of verapamil. Am J Physiol 1988; 254: F425–31PubMedGoogle Scholar
  39. 39.
    Whitty MR, Jackson B. Diabetic nephropathy in the rat: differing renal effects of an angiotensin converting enzyme inhibitor and a calcium inhibitor. Diabetes Res 1988; 8: 91–6PubMedGoogle Scholar
  40. 40.
    Dworkin LD, Benstein JA. Impact of antihypertensive therapy on progressive kidney damage. Am J Hypertens 1989; 2 Suppl.: 162–72Google Scholar
  41. 41.
    Bakris GL. Effects of diltiazem or lisinopril on massive proteinuria associated with diabetes mellitus. Ann Intern Med 1990; 112: 707–8PubMedGoogle Scholar
  42. 42.
    Bakris GL. Diltiazem decreases urinary protein excretion in patients with diabetes nephropathy [abstract]. Am J Hypertens 1990; 3: 97Google Scholar
  43. 43.
    Melbourne Diabetic Nephropathy Study Group. Comparison between Perindopril and nifedipine in hypertensive and normotensive diabetic patients with microalbuminuria. BMJ 1991; 302: 210–6CrossRefGoogle Scholar
  44. 44.
    Jerums G, Allen TJ, Tsalamandris C, et al. Angiotensin converting enzyme inhibition and calcium channel blockade in incipient diabetic nephropathy. Kidney Int 1992; 41: 904–11PubMedCrossRefGoogle Scholar
  45. 45.
    Reams GP, Hamory A, Lau A, et al. Effect of nifedipine on renal function in patients with essential hypertension. Hypertension 1988; 11: 452–6PubMedCrossRefGoogle Scholar
  46. 46.
    Ferrier C, Ferrari P, Weidmann P, et al. Antihypertensive therapy with the calcium-channel-blocker verapamil and/or the angiotensin-converting-enzyme-inhibitor enalapril in diabetic patients. Diabetes Care 1991; 14: 911–4PubMedCrossRefGoogle Scholar
  47. 47.
    Mimran A, Insua A, Ribstein J, et al. Comparative effects of Captopril and nifedipine in normotensive patients with incipient diabetic nephropathy. Diabetes Care 1988; 11: 850–3PubMedCrossRefGoogle Scholar
  48. 48.
    Bauer JH, Reams GP. Do calcium antagonists protect the human hypertensive kidney? Am J Hypertens 1989; 2 Suppl.: 173–8Google Scholar
  49. 49.
    De Marie BK, Bakris GC. Effects of different classes of calcium antagonists on proteinuria in diabetic subjects. Ann Intern Med 1990; 113: 987–8Google Scholar
  50. 50.
    Burges RA, Dodd MG. Amlodipine. Drugs Rev 1990; 8: 25–44Google Scholar
  51. 51.
    National Diabetes Data Group. Classification and diagnosis of diabetes mellitus and other categories of glucose intolerance. Diabetes 1979; 281: 1039–57Google Scholar
  52. 52.
    Christensen C, Mogensen CE. Effect of antihypertensive treatment on progression of incipient diabetic nephropathy. Hypertension 1985; 7 Suppl. II: 109–13Google Scholar
  53. 53.
    Loutzenhiser RD, Epstein M, Horton C, et al. Reversal by the calcium-antagonist nisoldipine of norepinephrine-induced reduction of GFR: evidence for preferential antagonism on pre-glomerular vasoconstriction. J Pharmacol Exp Ther 1985; 232: 382–7PubMedGoogle Scholar
  54. 54.
    Loutzenhiser RD, Epstein M, Fischetti F, et al. Effects of amlodipine on renal haemodynamics. Am J Cardiol 1989; 64: 122–81CrossRefGoogle Scholar
  55. 55.
    Epstein M. Calcium antagonists and the kidney. Implications for renal protection. Am J Hypertens 1991; 4: 482–6SGoogle Scholar
  56. 56.
    Raij L, Keane WF, Oswald H, et al. Glomerular mesangium function and relationship to angiotensin II. Am J Med 1985; 79 Suppl. 3c: 24–30PubMedCrossRefGoogle Scholar
  57. 57.
    Morelli E, Loon N, Meyer T, et al. Effects of converting enzyme inhibition on barrier function in diabetic glomerulopathy. Diabetes 1990; 39: 76–82PubMedCrossRefGoogle Scholar
  58. 58.
    Remuzzi A, Puntorieri S, Battaglia C, et al. Angiotensin converting enzyme inhibition ameliorates glomerular filtration of macromolecules and water and lessens glomerular injury in the rat. J Clin Invest 1990; 85: 54–9CrossRefGoogle Scholar
  59. 59.
    Schultz PJ, Raij L. Inhibition of human mesangial cell proliferation by calcium channel blockers. Hypertension 1990; 15 Suppl. I: 76–80CrossRefGoogle Scholar

Copyright information

© Adis International Limited 1997

Authors and Affiliations

  • Roberto Fogari
    • 1
  • A. Zoppi
    • 1
  • G. D. Malamani
    • 1
  • P. Lusardi
    • 1
  • M. Destro
    • 1
  • L. Corradi
    • 1
  1. 1.Department of Internal Medicine and TherapeuticsUniversity of PaviaPaviaItaly

Personalised recommendations