Long-term effects of metformin on metabolism and microvascular and macrovascular disease in patients with type 2 diabetes mellitus

Archives of Internal Medicine

Volumn 169, Issue 6, 2009, Pages 616-625

  Kooy, Adriaan ^a,g   De Jager, Jolien ^a,b   Lehert, Philippe ^c   Bets, Daniel ^d   Wulffelé, Michiel G ^a   Donker, Ab J M ^e   Stehouwer, Coen D A ^f  

^a Bethesda Hospital   (Netherlands)

^b ACADEMIC MEDICAL CENTER   (Netherlands)

^c FACULTÉ POLYTECHNIQUE DE MONS   (Belgium)

^d Clinical Research and Development   (Netherlands)

^e VU UNIVERSITY MEDICAL CENTER   (Netherlands)

^f MAASTRICHT UNIVERSITY MEDICAL CENTER   (Netherlands)

^g Bethesda Diabetes Research Center   (Netherlands)

Author keywords

[No Author keywords available]

Indexed keywords

HEMOGLOBIN A1C; INSULIN; LIPID; METFORMIN; PLACEBO;

ADD ON THERAPY; ADULT; AGED; ARTICLE; BLOOD PRESSURE; BODY MASS; BODY WEIGHT; CARDIOVASCULAR DISEASE; CARDIOVASCULAR EFFECT; CLINICAL TRIAL; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; DIARRHEA; DRUG DOSE TITRATION; DRUG EFFECT; DRUG METABOLISM; DRUG WITHDRAWAL; FATIGUE; FEMALE; FLATULENCE; FOLLOW UP; GLYCEMIC CONTROL; HEADACHE; HEARTBURN; HUMAN; INSULIN TREATMENT; LIPID BLOOD LEVEL; MAJOR CLINICAL STUDY; MALE; MICROANGIOPATHY; MORBIDITY; MORTALITY; MULTICENTER STUDY; NAUSEA; NON INSULIN DEPENDENT DIABETES MELLITUS; OUTPATIENT DEPARTMENT; PRIORITY JOURNAL; PRURITUS; RANDOMIZED CONTROLLED TRIAL; WEIGHT GAIN;

ADULT; AGED; AGED, 80 AND OVER; BLOOD PRESSURE; DIABETES MELLITUS, TYPE 2; DIABETIC ANGIOPATHIES; DRUG THERAPY, COMBINATION; FEMALE; FOLLOW-UP STUDIES; HEMOGLOBIN A, GLYCOSYLATED; HUMANS; HYPOGLYCEMIA; HYPOGLYCEMIC AGENTS; INSULIN; LIPIDS; MALE; METFORMIN; MIDDLE AGED; WEIGHT GAIN;

EID: 63849328978     PISSN: 00039926     EISSN: 15383679     Source Type: Journal    
DOI: 10.1001/archinternmed.2009.20     Document Type: Article

References (39)

1. Bonow RO, Gheorghiade M. The diabetes epidemic: a national and global crisis. Am J Med. 2004;116(suppl 5A):2S-10S.
2. U.K. Prospective Diabetes Study (UKPDS) Group. Effect of intensive blood- glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). Lancet. 1998;352(9131):854-865.
3. Evans JMM, Ogston SA, Emslie-Smith A, Morris AD. Risk of mortality and adverse cardiovascular outcomes in type 2 diabetes: a comparison of patients treated with sulfonylureas and metformin. Diabetologia. 2006;49(5):930-936.
4. Johnson JA, Simpson SH, Toth WL, Majumdar SR. Reduced cardiovascular morbidity and mortality associated with metformin use in subjects with type 2 diabetes. Diabet Med. 2005;22(4):497-502.
5. Kirpichnikov D, McFarlane SI, Sowers JR. Metformin: an update. Ann Intern Med. 2002;137(1):25-33.
6. Beisswenger PJ, Howell SK, Touchette AD, Lal S, Swerzgold BS. Metformin reduces systemic methylglyoxal levels in type 2 diabetes. Diabetes. 1999;48(1):198-202.
7. De Jager J, Kooy A, Lehert P, et al. Effects of short-term treatment with metformin on markers of endothelial function and inflammatory activity in type 2 diabetes mellitus: a randomised, placebo-controlled trial. J Intern Med. 2005;257(1):100-109.
8. Marre M. Before oral agents fail: the case for starting insulin early. Int J Obes Relat Metab Disord. 2002;26(suppl 3):S25-S30.
9. Aviles-Santa L, Sinding J, Raskin P. Effects of metformin in patients with poorly controlled insulin-treated type 2 diabetes mellitus: a randomized, double-blind, placebo-controlled trial. Ann Intern Med. 1999;131(3):182-188.
10. Yki-Järvinen H, Ryysy L, Nikkilä K, Tulokas T, Vanamo R, Heikkilä M. Comparison of bedtime insulin regimens in patients with type 2 diabetes mellitus: a randomized, controlled trial. Ann Intern Med. 1999;130(5):389-396.
11. Wulffelé MG, Kooy A, Lehert P, et al. Combination of insulin and metformin in the treatment of type 2 diabetes. Diabetes Care. 2002;25(12):2133-2140.
12. Valk GD, Nauta JJP, Strijers RLM, Bertelsmann FW. Clinical examination versus neurophysiological examination in the diagnosis of diabetic polyneuropathy. Dia- bet Med. 1992;9(8):716-721.
13. Bonadonna RC, Cucinotta D, Fedele D, Riccardi G, Tiengo A; Metascreen Writing Committee. The metabolic syndrome is a risk indicator of microvascular and macrovascular complications in diabetes: results from Metascreen, a multi-center diabetes clinic-based survey. Diabetes Care. 2006;29(12):2701-2707.
14. de Jager J, Dekker JM, Kooy A, et al. Endothelial dysfunction and low-grade inflammation explain much of the excess cardiovascular mortality in individuals with type 2 diabetes: the Hoorn study. Arterioscler Thromb Vasc Biol. 2006; 26(5):1086-1093.
15. Nguyen TT, Wong TY. Retinal vascular manifestations of metabolic disorders. TrendsEndocrinolMetab. 2006;17(7):262-268.
16. Frison L, Pocock SJ. Repeated measures in clinical trials: analysis using mean summary statistics and its implications for design. Stat Med. 1992;11(13):1685-1704.
17. Qiou Z, Ravishanker N, Dey DK. Multivariate survival analysis with positive stable frailties. Biometrics. 1999;55(2):637-644.
18. Wulffele MG, Kooy A, Lehert P, Bets D, Donker AJM, Stehouwer CDA. Does metformin decrease blood pressure in patients with type 2 diabetes intensively treated with insulin? DiabetMed. 2005;22(7):907-913.
19. Granberry MC, Fonseca VA. Cardiovascular risk factors associated with insulin resistance: effects of oral antidiabetic agents. Am J Cardiovasc Drugs. 2005;5(3):201-209.
20. Schäfers RF. Do effects on blood pressure contribute to improved clinical outcomes with metformin? Diabetes Metab. 2003;29(4, pt 2):6S62-6S70.
21. Wulffelé MG, Kooy A, de Zeeuw D, Stehouwer CDA, Gansevoort RT. The effect of metformin on blood pressure, plasma cholesterol, and triglycerides in type 2 diabetes mellitus: asystematic review. J Intern Med. 2004;256(1):1-14.
22. Rodríguez-Moctezuma JR, Robles-Lopez G, Lopez-Carmona JM, Gutierrez- Rosas MJ. Effects of metformin on the body composition in subjects with risk factors for type 2 diabetes. Diabetes Obes Metab. 2005;7(2):189-192.
23. Graber AL, Shintani AK, Wolff K, Brown A, Elasy TA. Glycemic relapse in type 2 diabetes. Endocr Pract. 2006;12(2):145-151.
24. UK Prospective Diabetes Study (UKPDS) Group. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet. 1998; 352(9131):837-853.
25. Phillips LS, Branch WT, Cook CB, et al. Clinical inertia. Ann Intern Med. 2001;135 (9):825-834.
26. Grant R, Adams AS, Trinacty CM, et al. Relationship between patient medication adherence and subsequent clinical inertia in type 2 diabetes glycemic management. Diabetes Care. 2007;30(4):807-812.
27. Natali A, Ferrannini E. Effects of metformin and thiazolidinediones on suppression of hepatic glucose production and stimulation of glucose uptake in type 2 diabetes: a systematic review. Diabetologia. 2006;49(3):434-441.
28. Migoya EM, Miller J, Larson P. Sitagliptin, a selective DPP-4 inhibitor, and metformin have complementary effects to increase active GLP-1 concentrations. Oral presentation at: 67th Annual Meeting of the American Diabetes Association; June 2007; Chicago, IL; A74.
29. Vaag AA. Glycemic control and prevention of microvascular and macrovascular disease in the Steno 2 study. Endocr Pract. 2006;12(suppl 1):89-92.
30. U.K. Prospective Diabetes Study (UKPDS) Group. Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 38. BMJ. 1998;317(7160):703-713.
31. Misra A, Kumar S, Vikram NK, Kumar A. The role of lipids in the development of diabetic microvascular complications: implications for therapy. Am J Cardio-vasc Drugs. 2003;3(5):325-338.
32. Caballero AE, Delgado A, Aguilar-Salinas CA, et al. The differential effects of metformin on markers of endothelial activation and inflammation in subjects with impaired glucose tolerance: a placebo-controlled, randomized clinical trial. J Clin Endocrinol Metab. 2004;89(8):3943-3948.
33. Jager A, van Hinsbergh VWM, Kostense PJ, et al. Von Willebrand factor, C- reactive protein, and 5-year mortality in diabetic and non-diabetic subjects: The Hoorn Study. Arterioscler Thromb Vasc Biol. 1999;19(12):3071-3078.
34. Jager A, van Hinsbergh VWM, Kostense PJ, et al. Increased levels of soluble vascular cell adhesion molecule 1 are associated with risk of cardiovascular mortality in type 2 diabetes: the Hoorn study. Diabetes. 2000;49(3):485-491.
35. Danesh J, Wheeler JG, Hieshfield GM, et al. C-reactive protein and other circulating markers of inflammation in the prediction of coronary heart disease. N Engl J Med. 2004;350(14):1387-1397.
36. Tanaka Y, Uchino H, Shimizu T, et al. Effect of metformin on advanced glycation endproduct formation and peripheral nerve function in streptozotocin-induced diabetic rats. Eur J Pharmacol. 1999;376(1-2):17-22.
37. Fruehwald-Schultes B, Oltmanns KM, Toschek B, et al. Short-term treatment with metformin decreases serum leptin concentration without affecting body weight and body fat content in normal-weight healthy men. Metabolism. 2002;51(4): 531-536.
38. Krishnan STM, Baker NR, Carrington AL, Raymann G. Comparative roles of microvascular and nerve function in foot ulceration in type 2 diabetes. Diabetes Care. 2004;27(6):1343-1348.
39. Murphie P. Macrovascular disease aetiology and diabetic foot ulceration. J Wound Care. 2001;10(4):103-107.