European Journal of Clinical Pharmacology

, Volume 44, Issue 2, pp 107–112 | Cite as

Metformin for obese, insulin-treated diabetic patients: improvement in glycaemic control and reduction of metabolic risk factors

  • D. Giugliano
  • A. Quatraro
  • G. Consoli
  • A. Minei
  • A. Ceriello
  • N. De Rosa
  • F. D'Onofrio
Originals

Summary

The efficacy and safety of metformin in the treatment of obese, non-insulin-dependent, diabetic subjects poorly controlled by insulin after secondary failure to respond to sulphonylureas has been investigated. Fifty insulin-treated, obese diabetics participated in this prospective, randomised double-blind six-month trial. After a four-week run-in period, during which all patients were given placebo (single-blind), patients were randomly assigned to continue to receive placebo or to active treatment with metformin.

At six months, there was a relevant and significant improvement in glycaemic control in diabetics receiving the combined insulin-metformin treatment (decrease in glucose −4.1 mmol·l−1; glycosylated haemoglobin A1 decrease −1.84%). No significant changes were seen in diabetics receiving insulin and placebo. There was a significant decrease in blood lipids (trygliceride and cholesterol), an increase in HDL-cholesterol and a reduction in blood pressure in diabetics taking metformin. These postive findings were most marked in the 14 diabetics who experienced a good response to metformin (glucose profile <10 mmol·l−1), and were less marked but still significant in the remaining 13 diabetics, whose response to therapy was not so good (glucose profile >10 mmol·l−1). The fasting insulin level was significantly lower after six months of combined insulin-metformin treatment as shown by a 25% reduction in the daily dose of insulin (−21.6 U/day).

Metformin was well tolerated by all diabetics. Combining metforming with insulin in obese, insulin-treated and poorly controlled diabetics may represent a safe strategy to achieve better glycaemic control with a reduction in certain metabolic risk factors associated with the increased incidence of cardiovascular disease in diabetes mellitus.

Key words

Metformin Diabetes mellitus noninsulin-dependent secondary failure to sulphonylureas combined therapy glucose homoeostasis plasma lipids blood pressure adverse effects 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Morris RD, Rimm DL, Hartz AJ, Kalkhoff RK, Rimm A (1989) Obesity and heredity in the etiology of non-insulin-dependent diabetes mellitus in 32,662 adults white women. Am J Epidemiol 130: 112–120Google Scholar
  2. 2.
    Wolfenbuttel BHR, Weber RFA, Van Koetsveld PM, Verschoor L (1989) Limitations of diet therapy in patients with non-insulin-dependent diabetes mellitus. Int J Obesity 13: 173–182Google Scholar
  3. 3.
    Groop LC, Pelkonen R, Koskimies S, Bottazzo GF, Doniach D (1986) Secondary failure to treatment with oral antidiabetic agents in non-insulin-dependent diabetes. Diabetes Care 9: 129–133Google Scholar
  4. 4.
    Laasko M, Sarlund H, Pyorrala K (1986) Prevalence of insulin deficiency among initially non-insulin-dependent middle-aged diabetic individuals. Diabetes Care 9: 228–231Google Scholar
  5. 5.
    Foley JE, Kashiwagi A, Verso MA, Reaven G, Andrews J (1983) Improvement of in vitro insulin action after one month of insulin therapy in obese non-insulin dependent diabetics. J Clin Invest 72: 1901–1909Google Scholar
  6. 6.
    Stout RW (1979) Diabetes and atherosclerosis: the role of insulin. Diabetologia 16: 141–150Google Scholar
  7. 7.
    Scheen AJ, Lefebvre PJ (1989) Insulin versus insulin plus sulfonylureas in type-2 diabetic patients with secondary failure to sulfonylureas. Diabetes Res Clin Pr 6: S33-S43Google Scholar
  8. 8.
    Bailey CJ (1988) Metformin revisited: its action and indications for use. Diabetic Med 5: 315–320Google Scholar
  9. 9.
    Giugliano D, Cozzolino D, Salvatore T, Torella R, Franchimont P, D'Onofrio F, Lefebvre PJ (1988) Altered metabolic and hormonal responses to epinephrine and beta-endorphin in human obesity. J Clin Endocrinol Metab 67: 238–244Google Scholar
  10. 10.
    Walter E (1980) Biomathematik für Mediziner 2nd ed. Teubner, StuttgartGoogle Scholar
  11. 11.
    Olefsky JM, Kolterman OG (1981) Mechanism of insulin resistance in obesity and non-insulin-dependent (Type II) diabetes Am J Med 70: 151–168Google Scholar
  12. 12.
    Lebovitz HE (1990) Diabetes mellitus: theory and practice. In: Rifkin H, Porte D Jr (eds) Elsevier, New York, pp 554–574Google Scholar
  13. 13.
    Reaven GM, Chen YDI, Coulston AM, Greenfield MS, Hollenbeck C, Lardinois GC, Schwartz H (1983) Insulin secretion and action in non-insulin-dependent diabetes mellitus: is insulin resistance secondary to hyperinsulinaemia? Am J Med 75 [Suppl 5B]: 85–93Google Scholar
  14. 14.
    Bailey TS, Mezitis NHE (1990) Combination therapy with insulin and sulfonylureas for type-II diabetes. Diabetes Care 13: 687–695Google Scholar
  15. 15.
    Jackson RA, Hawa MI, Jaspan JB, Sim BM, Di Silvio M, Featherbe D (1987) Mechanism of metformin action in non-insulin-dependent diabetes. Diabetes 36: 636–640Google Scholar
  16. 16.
    Swislocki ALM, Hoffman BB, Reaven GM (1989) Insulin resistance, glucose intolerance and hyperinsulinaemia in patients with hypertension. Am J Hypertension 2: 419–423Google Scholar
  17. 17.
    Natali A, Santoro D, Palombo C, Ghione S, Ferrannini E (1990) Diabetes and high blood pressure. Diabetes Nutr Metab 3: 67–84Google Scholar
  18. 18.
    Landin K, Tengborn L, Smith U (1991) Treating insulin resistance in hypertension with metformin reduces both blood pressure and metabolic risk factors. J Intern Med 229: 181–187Google Scholar
  19. 19.
    Schneider J (1991) Effects of metformin on dyslipoproteinemia in non-insulin-depentend diabetes mellitus. Diabete Metab 17: 185–190Google Scholar
  20. 20.
    Hulley SB, Roseman RH, Bawol RD, Brand RJ (1980) Epidemiology as a guide to clinical decisions. The association between triglyceride and coronary heart disease. N Engl J Med 302: 1383–1389Google Scholar
  21. 21.
    Austin MA (1989) Plasma triglyceride as a risk factor for coronary heart disease: The epidemiological evidence and beyond. Am J Epidemiol 129: 249–259Google Scholar
  22. 22.
    Castelli WP (1986) The triglyceride issue: a view from Framingham. Am Heart J 112: 432–440Google Scholar
  23. 23.
    Reaven GM, Chen Y-DI (1988) Role of insulin in regulation of lipoprotein metabolism in diabetes. Diabetes/Metab Rev 4: 639–652Google Scholar
  24. 24.
    Zavaroni I, Dell'Aglio E, Bonora E, Alpi O, Passeri M, Reaven GM (1987) Evidence that multiple risk factors for coronary artery disease exist in persons with abnormal glucose tolerance. Am J Med. 83: 609–612Google Scholar
  25. 25.
    Reaven GM (1988) Role of insulin resistance in human disease. Diabetes 37: 1495–1607Google Scholar
  26. 26.
    Kannel WB, McGee DL (1979) Diabetes and cardiovascular disease. The Framingham Study. JAMA 241: 2035–2038Google Scholar
  27. 27.
    Quatraro A, Giugliano D, Minei A, et al. (1990) Incidence of cardiovascular complications in elderly diabetic patients. 2nd International Congress on Hypertension in the Elderly: Focus on Risk Factors. Rome, 90AGoogle Scholar
  28. 28.
    Hollenbeck CB, Johnston P, Varasteh BB, Chen Y-DI, Reaven GM (1991) Effects of metformin on glucose, insulin and lipid metabolism in patients with mild hypertriglyceridemia and non-insulin dependent diabetes by glucose tolerance test criteria. Diabete Metab 5: 483–489Google Scholar
  29. 29.
    Stout RW (1990) Insulin and atheroma: a 20-yr perspective. Diabetes Care 13: 631–654Google Scholar

Copyright information

© Springer-Verlag 1993

Authors and Affiliations

  • D. Giugliano
    • 1
  • A. Quatraro
    • 2
  • G. Consoli
    • 2
  • A. Minei
    • 2
  • A. Ceriello
    • 3
  • N. De Rosa
    • 1
  • F. D'Onofrio
    • 1
  1. 1.Department of Geriatrics and Metabolic Diseases, First Faculty of MedicineUniversity of NaplesItaly
  2. 2.Diabetic Clinic S. RitaTarantoItaly
  3. 3.Institute of Internal MedicineUniversity of UdineItaly

Personalised recommendations