書籍詳細

I. 糖尿病の薬物療法

P.20 掲載の参考文献

• 1) Weyer C et al:The natural history of insulin secretory dysfunction and insulin resistance in the pathogenesis of type 2 diabetes mellitus. J Clin Invest 104:787-794, 1999
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• 2) Kawamori R et al:Study of glucose tolerance and the dynamic property of insulin secretion. Analysis of intravenous glucose tolerance test with the aid of control theory. Acta Endocrinol(Copenh) 90:283-294, 1979
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• 3) Uchino H et al:Impairment of early insulin response after glucose load, rather than insulin resistance, is responsible for postprandial hyperglycemia seen in obese type 2 diabetes:Assessment using Nateglinide, a new insulin secretagogue. Endocr J 47:639-641, 2000
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• 4) Kawamori R et al:Mechanism of exercise-induced hypoglycemia in depancreatized dogs, maintained on long acting insulin. J Clin Invest 59:331-337, 1977
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• 5) Zhou G et al:Role of AMP-activated protein kinase in mechanism of metformin action. J Clin Invest 108:1167-1174, 2001
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P.28 掲載の参考文献

• 1) Chiasson JL et al:A STOP-NIDDM Group:Acarbose for prevention of type 2 diabetes mellitus:the STOP-NIDDM randomized trial. Lancet 359:2072-2077, 2002
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• 2) Chiasson JL et al:ASTOP-NIDDM Group:Acarbose treatment and the risk of cardiovascular disease and hypertension in patients with impaired glucose tolerance:the STOP-NIDDM trial. JAMA 290:486-494, 2003

• 3) Hirose T et al:The effects of nateglinide following oral glucose load in impaired glucose tolerance subjects:rapid insulin stimulation by nateglinide in IGT subjects. Endocr J 49:649-665, 2002
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• 4) Uchino H et al:Impairment of early insulin response after glucose load rather than insulin resistance, is responsible for postprandial hyperglycemia seen in obese type 2 diabetes:assessment using nateglinide, a new insulin secretagogue. Endocr J 47:639-641, 2000
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• 5) Knowler WC et al:Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med 346:393-403, 2002

• 6) Diabetes Prevention Program Research Group:Effects of withdrawal from metformin on the development of diabetes in the prevention program. Diabetes Care 26:977-980, 2003

• 7) 弘世貴久, 河盛隆造監修:糖尿病の治療. (医療情報科学研究所編:病気がみえる Vol.3代謝・内分泌疾患), メディックメディア, 東京, 2004

P.36 掲載の参考文献

• 1) 小坂樹徳:II糖尿病の臨床・治療F糖尿病の治療 (各論3) d ビグアナイド剤治療 新内科学大系 第46巻B (代謝異常 IIb) (吉利 和, 中尾喜久ら監修), 中山書店, 1975

• 2) DeFronzo RA et al:Efficacy of metformin in patients with non-insulin-dependent diabetes mellitus. The Multicenter Metformin Study Group. N Engl J Med 333:541-549, 1995

• 3) UK Prospective Diabetes Study (UKPDS) Group:The Lancet 352:854, 1998

• 4) Misbin RI:Phenformin-associated lactic acidosis:pathogenesis and treatment. Ann Intern Med 87:591-595, 1977
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• 5) Luft D et al:Lactic acidosis in biguanide-treated diabetics:areview of 330 cases. Diabetologia 14:75-87, 1978

• 6) Anisimov VN et al:Insulin and longevity:antidiabetic biguanides as geroprotectors. Biogerontology 4:297-307, 2003
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• 7) 松田昌文, 加来浩平:第3章 "どんな疾患があるのか" 乳酸アシドーシス, 看護のための最新医学講座 糖尿病と合併症 (日野原重明, 井村裕夫監修), 中山書店, 東京, 2001, pp312-318

• 8) Goldner MG et al:EffectS of hypoglycemic agentS on vascular complications in patients with adult-onset diabetes. 3. Clinical implications of UGDP results. JAMA 218:1400-1410, 1971
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• 9) Knatterud GL et al:Effects of hypoglycemic agents on vascular complications in patients with adult-onset diabetes. IV. A preliminary report on phenoformin results. JAMA 217:777-784, 1971

• 10) The University Group Diabetes Program. A study of the effects of hypoglycemic agents on vascular complications in patients with adult-onset diabetes. V. Evaluation of phenformin therapy. Diabetes 24(Suppl 1):65-184, 1975

• 11) Berger W:Incidence of severe side effects during therapy with sulfonylureas and biguanides. Horm Metab Res Suppl 15:111-115, 1985
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• 12) Campbell IW:Metformin and the sulphonylureas:the comparative risk. Horm Metab Res Suppl 15:105-111, 1985
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• 13) Misbin RI et al:Lactic acidosis in patients with diabetes treated with metformin. N Engl J Med 338:265-266, 1998
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• 14) Turner RC et al:Insulin deficiency and insulin resistance interaction in diabetes:estimation of their relative contribution by feedback analysis from basal plasma insulin and glucose concentrations. Metabolism 28:1086-1096, 1979
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• 15) DeFronzo RA et al:Glucose clamp technique:a method for quantifying insulin secretion and resistance. Am J Physiol 237:E214-E223, 1979
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• 16) Bergman RN et al:Quantitative estimation of insulin sensitivity. Am J physiol 236:E667-E677, 1979
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• 17) Wysowski DK et al:Rapid increase in the use of oral antidiabetic drugs in the United States, 1990-2001. Diabetes Care 26:1852-1855, 2003
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II. メトホルミンの再評価と理由

P.40 掲載の参考文献

• 1) Bailey CJ et al:Metformin revisited:its actions and indications for use. Diabet Med 5:315-320, 1988
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• 2) DeFronzo R et al:Efficacy of metformin in NIDDM patients poorly controlled on diet alone or diet plus sulfonyl urea. N Engl J Med 333:541-549, 1995
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• 3) Garber A et al:Efficacy of metfirmin type II diabetes-results of a double-blind, placebo-controlled, dose-response trial. Am J Med 102:491-497, 1997

• 4) Diabetes Prevention Program Research Group:Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med 346:393-403, 2002
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• 5) Iwai H et al:Type2 diabetes mellitus with lactic acidosis and acute renal failure induced by metformin overdose in suicide. J Japan Diab Soc 47:439-445, 2004

• 6) Enzo B et al:Lack of effect of intravenous metformin on plasma concentrations of glucose, insulin, C-peptide, glucagons and groWth hormone in non-diabetic subjects. Curr Med Res Opin 9:47-51, 1984

• 7) Zitzmann S et al:Severe hypoglycemia in an elderly patient treated with metformin. Int J Clin Pharmacol Ther 40:108-110, 2002

P.46 掲載の参考文献

• 1) Bailey CJ et al:Drug therapy:Metformin. N Engl J Med 334:574-579, 1996
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• 2) United Kingdom Prospective Diabetes Study Group:United Kingdom prospective diabetes study (UKPDS) 13:relative efficacy of randomly allocated diet, sulfonylurea, insulin, or metformin in patients with newly diagnosed non-insulin dependent diabetes followed for three years. BMJ 310:83-88, 1995
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• 3) Bailey CJ et al:Anorectic effect of metformin in lean and genetically obese hyperglycemic(ob/ob) mice. Arch Int Phannacodyn Ther 282:233-239, 1986

• 4) Paolisso G et al:Effect of metformin on food intake in obese subjects. Eur J Clin Invest 28:441-446, 1998
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• 5) 清水弘行ほか:2型糖尿病症例への塩酸メトフォルミン治療による体重変動への影響. Prog Med 22:450-453, 2002
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• 6) Hermann LS:Metformin. A review of its pharmacological properties and therapeutic use. Diabete Metab 5:233-245, 1979
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• 7) Davidson MB et al:An overview of metformin in the treatment of type 2 diabetes mellitus. Am J Med 102:99-110, 1997
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• 8) Campbell IW et al:Worldwide experience of metformin as an effective glucose-lowering agent:a meta-analysis. Diabetes Metab Rev 11:S57-S62, 1995
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• 9) Johansen K:Efficacy of metformin in the treatment of NIDDM. Meta-analysis. Diabetes Care 22:33-37, 1999
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• 10) DeFronzo RA, Goodman AM, and the Multicenter Metformin Study Group:Efficacy of metformin in patients with non-insulin-dependent diabetes Mellitus. N Engl J Med 333:541-549, 1995

• 11) Glueck CJ et al:Metformin reduces weight, central obesity, insulin, leptin, and low-density lipoprotein cholesterol in nondiabetic, morbidly obese subjects with body mass index greater than 30. Metabolism 50:856-861, 2001

P.50 掲載の参考文献

• 1) Stumvoll M et al:Metabolic effects of metformln in non-insulin-dependent diabetes mellitus. N Engl J Med 333:550-554, 1995
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• 2) Inzucchi SE et al:Efficacy and metabolic effects of metformin and troglitazone in type II diabetes mellitus. N Engl J Med 338:867-872, 1998
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• 3) Zhou G et al:Role of AMP-activated protein kinase in mechanism of metformin action. J Clin Invest 108(8):1167-1174, 2001
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• 4) Musi N et al:Metformin increases AMP-activated protein kinase activity in skeletal muscle of subjects with type 2 diabetes. Diabetes 51:2074-2081, 2002
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• 5) Mu J et al:Arole for AMP-activated protein kinase in contraction-and hypoxia-regulated glucose transport in skeletal muscle. Mol Cell 7:1085-1094, 2001

• 6) Li Y et al:Inhibition of phosphoenolpyruvate carboxykinase gene expression by metformin in cultured hepatocytes. Chin Med J 115(12):1843-1848, 2002

• 7) Howley SA et al:The antidiabetic drug metformin activates the AMP-activated protein kinase cascade via an adenine nucleotide-independent mechanism. Diabetes 51:2420-2425, 2002

• 8) Stith BJ et al:The antidiabetic drug metformin elevates receptor tyrosine kinase activity and inositol 1, 4, 5-triphosphate mass in Xenopus oocytes. Endocrinology 137:2990-2999, 1996
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• 9) Gunton JE et al:Metformin rapidly increase insulin receptor activation in human liver and signals preferentially through insulin-receptor substrate-2. J Clin Endocrinol Metab 88(3):1323-1332, 2003
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• 10) Bailey C et al:Importance of the intestine as a site of metformin-stimulated glucose utilization. Br J Pharmacol 112:671-675, 1994
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• 11) De Leo X et al:Insulin-lowering agents in the management of polycystic ovary syndrome. Endocrine Rev 24:633-667, 2003

P.56 掲載の参考文献

• 1) DeFronzo RA et al:Mechanism of metformin action in obese and lean noninsulin-dependent diabetic subjects. J Clin Endocrinol Metab 73:1294-1301, 1991
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• 2) Hermann LS et al:Therapeutic comparison of metformin and sulfonylurea, alone and in various combinations. A double-blind controlled study. Diabetes Care 17:1100-1109, 1994
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• 3) Chan JCN et al:Metabolic and hemodynamic effects of metformin and glibenclamide in normotensive NIDDM patients. Diabetes Care 16:1035-1038, 1993

• 4) Jeppesen J et al:Effect of metformin on postprandial lipemia in patients with fairly to poorly controlled NIDDM. Diabetes Care 17:1093-1099, 1994
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• 5) DeFronzo RA et al:Efficacy of metformin in patients with non-insulin-dependent diabetes mellitus. The Multicenter Metformin Study Group. N Engl J Med 333:541-549, 1995

• 6) Wulffele MG et al:The effect of metformin on blood pressure, plasma cholesterol and triglycerides in type2 diabetes mellitus:a systematic review. J Intern Med 256:1-14, 2004

• 7) Giugliano D et al:Metformin improves glucose lipid metabolism, and reduces blood pressure in hypertensive, obese women. Diabetes Care 16:1387-1390, 1993
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• 8) Relimpio F et al:Adding metformin versus insulin does increase in insulin-treated but poorly controlled Type 2 diabetes mellitus:an open-label randomized trial. Diabet Med 15:997-1002, 1998
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• 9) Hanefeld M, Brunetti P, Schemthaner GH, Matthews DR, Charbonnel BH; QUARTET Study Group:One-year glycemic control with a sulfonylurea plus pioglitazone versus a sulfonylurea plus metformin in patients with type 2 diabetes. Diabetes Care 27:141-147, 2004

• 10) Zhou G et al:Role of AMP-avtivated protein kinase in mechanism of Metformin action. J Clin Invest 108:1167-1174, 2001

• 11) Musi N et al:Metformin increases AMP-activated protein kinase activity in skeletal muscle of subjects with type 2 diabetes. Diabetes 51:2074-2081, 2002
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P.63 掲載の参考文献

• 1) Tsikouris JP et al:Plasminogen activator inhibitor-1:physiologic role, regulation, and the influence of common pharmacologic agents. J Clin Pharmacol 42:1187-1199, 2002
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• 2) Anfosso F et al:Plasminogen activator inhibitor-1 synthesis in the human hepatoma cell line Hep G2. Metformin inhibits the stimulating effect of insulin. J Clin Invest 91:2185-2193, 1993
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• 3) vaughan DE:Angiotensin and vascular fibrinolytic balance. Am J Hypertens 15:3S-8S, 2002
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• 4) Lundgren CH et al:Elaboration of type-1 plasminogen activator inhibitor from adipocytes. A potential pathogenetic link between obesity and cardiovascular disease. Circulation 93:106-110, 1996
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• 5) Panahloo A et al:Determinants of plasminogen activator inhibitor 1 activity in treated NIDDM and its relation to a polymorphism in the plasminogen activator inhibitor 1 gene. Diabetes 44:37-42, 1995
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• 6) Shimomura I et al:Enhanced expression of PAI-1 in visceral fat:possible contributor to vascular disease in obesity. Nat Med 2:800-803, 1996
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• 7) Ma LJ et al:Prevention of obesity and insulin resistance in mice lacking plasminogen activator inhibitor 1. Diabetes 53:336-346, 2004
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• 8) Kao J et al:Relation of metfomin treatment to clinical events in diabetic patients undergoing Percutaneous intervention. Am J Cardiol 93:1347-1350, 2004

• 9) Juhan-Vague I et al:Increased plasma plasminogen activator inhibitor 1 levels. A possible link between insulin resistance and atherothrombosis. Diabetologia 34:457462, 1991

• 10) Nagi DK et al:Effects of metformin on insulin resistance, risk factors for cardiovascular disease, and plasminogen activator inhibitor in NIDDM sublects. A study of two ethnic groups. Diabetes Care 16:621-629, 1993

• 11) Cefalu WT et al:Effect of combination glipizide GITS/Metformin on fibrinolytic and metabolic parameters in poorly controlled type 2 diabetic subjects. Diabetes Care 25:2123-2128, 2002
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• 12) Gregorio F et al:Poorly controlled elderly Type 2 diabetic patients:the effects of increasing sulphonylurea dosages or adding metformin. Diabet Med 16:1016-1024, 1999
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• 13) Gin H et al:Effect of metformin on fibrinolytic parameters in insulin-treated, type 2 diabetic patients. Diabetes Metab 29:505-508, 2003
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• 14) He G et al:Metformin, but not thiazolidinediones, inhibits plasminogen activator inhibitor-1 production in human adipose tissue in Vitro. Horm Metab Res 35:18-23, 2003

• 15) Chu NV et al:Differential effects of metformin and troglitazone on cardiovascular hsk factors in patients with type 2 diabetes. Diabetes Care 25:542-549, 2002

• 16) Hadigan C et al:Increased PAI-1 and tPA antigen levels are reduced with metformin therapy in HIV-infected patients with fat redistribution and insulin resistance. J Clin Endocrinol Metab 86:939-943, 2001
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• 17) Grant PJ:The effects of high-and medium-dose metformin therapy on vascular risk factors in patients with type II diabetes. Diabetes Care 19:64-66, 1996

• 18) Montanari G et al:Treatment with low dose metformin in patients with peripheral vascular disease. Pharmacol Res 25:63-73, 1992
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• 19) UK Prospective Diabetes Study(UKPDS) Group:Effect of intensive blood-glucose control with metfomin on complications in overweight patients with type 2diabetes (UKPDS34). Lancet 352:854-865, 1998

P.69 掲載の参考文献

• 1) Soulis-Liparota T et al Retardation by aminoguanidine of development of albuminuria, mesangial expansion, and tissue fluorescence in streptozocin-induced diabetic rat. Diabetes 40:1328-1334, 1991
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• 2) Nakamura S et al:Progression of nephropathy in spontaneous diabetic rats is prevented by OPB-9195, a novel inhibitor of advanced glycation. Diabetes 46:895-899, 1997
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• 3) Hammes HP et al:Aminoguanidine treatment inhibits the development of experimental diabetic retinopathy. Proc Natl Acad Sci USA 88:11555-11558, 1991
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• 4) Brownlee M:Biochemistry and molecular cell biology of diabetic complications. Nature 414:813-820, 2001
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• 5) Baynes JW et al:Role of oxidative stress in diabetic complications:a new perspective on an old paradigm. Diabetes 48:1-9, 1999

• 6) Regan TJ et al:Left ventricular diastolic dysfunction in diabetic or hypertensive subjects:role of collagen alterations. Adv Exp Med Biol 498:127-132, 2001

• 7) Tanaka Y et al:Effect of metformin on advanced glycation endproduct formation and peripheral nerve function in streptozotocin-induced diabetic rats. Eur J Pharmacol 376:17-22, 1999
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• 8) Tanaka Y et al:Inhibitory effects of metformin on formation of advanced glycation end products. Curr Ther Res 58:693-697, 1997

• 9) Price DL et al:Chelating activity of advanced glycation end-product inhibitors. J Biol Chem 276:48967-48972, 2001
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• 10) Wiernsperger NF:Metformin:intrinsic vasculoprotective properties. Diabetes Technol Ther 2(2):259-272, 2000
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• 11) Beisswenger PJ et al:Metfomin reduces systemic methylglyoxal levels in type 2 diabetes. Diabetes 48:198-202, 1999

• 12) Ruggiero-Lopez D et al:Metformin reduces methylglyoxal levels by formation of a stable condensation product (Triazepinone). Diabetes 49 (suppl.I):A124, 2000

P.73 掲載の参考文献

• 1) 厚生省:国民栄養の現状 (平成10年度国民栄養調査結果) , 2000

• 2) Ludwig J et al:Nonalcoholic steatohepatitis:Mayo Clinic experiences with a hitherto unnamed disease. Mayo Clin Proc 55:434-438, 1980

• 3) Neuschwander-Tetri BA et al:Nonalcoholic steatohepatitis:Summary of an AASLD Single Topic Conference. Hepatology 37:1202-1219, 2003
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• 4) 西原利治ほか:非アルコール性脂肪肝炎 (NASH) の最近の話題. 日本内科学会雑誌 92:174-1109, 2003

• 5) Bugianesi E et al:Expanding the natural history of nonalcoholic steatohepatitis:from cryptogenic cirrhosis to hepatocellular carcinoma. Gastroenterology 123:134-140, 2002
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• 6) Zhou G et al:Role of AMP-activated protein kinase in mechanism of metformin action. J Clin Invest 108:1167-1174, 2001
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• 7) Lin HZ et al:Metformin reverses fatty liver disease in obese, leptin-deficient mice. Nat Med 6:998-1003, 2000
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P.81 掲載の参考文献

• 1) Bailey CJ et al Metformin. N Engl J Med 334:574-579, 1996
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• 2) Caspary VF et al:Analysis of the inhibitory effect of blguanldes on glucose absorption:inhibition of active sugar transport. Diabetologia 7:379-385, 1971

• 3) Ikeda T et al:Inhibitory effect of metformin on intestinal glucose absorption in the perfused rat intestine. Biochem Pharmacol 59:887-890, 2000
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• 4) Bailey CJ:Biguanides and NIDDM. Diabetes Care 15:755-772, 1992
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• 5) Wu MS et al:Effect of metformin on carbohydrate and lipoprotein metabolism in NIDDM patients. Diabetes Care 13:1-8, 1990
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• 6) Jackson RA et al:Mechanism of metformin action in non-insulin-dependent diabetes. Diabetes 36:632-640, 1987
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• 7) Penicaud L et al:Hypoglycaemic effect of metformin in genetically obese (fa/fa) rats results from an increased utilization of blood glucose by intestine. Biochem J 262:881-885, 1989
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• 8) Wilcock C et al:Sites of metformin-stimulated glucose metabolism. Biochem Pharmacol 39:1831-1834, 1990
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• 9) Bailey CJ et al:Importance of the intestine as a site of metformin-stimulated glucose utilization. Br J Pharmacol 112:671-675, 1994
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• 10) Lenzen S et al:Effect of metformin on SGLTI, GLUT2, and GLUT5 hexose transporter gene expression in small intestine from rats. Biochem Pharmacol 51:893-896, 1996

• 11) Matthaei S et al:Pathophysiology and pharmacological treatment of insulin resistance. Endocr Rev 21:585-618, 2000
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• 12) Mannucci E et al:Effect of metfomlin on glucagon-like peptide 1(GLP-1) and leptin levels in obese nondiabetic subjects. Diabetes Care 24:489-494, 2001
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• 13) Zander M et al:Additive glucose-lowering effects of glucagon-like peptide-1 and metformin in type 2 diabetes. Diabetes Care 24:720-725, 2001
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• 14) Yasuda N et al:Enhanced secretion of glucagon-like peptide 1 by biguanide compounds. Biochem Biophys Res Commun 298:779-784, 2002
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• 15) Yamazaki K et al:The combination of metfomin and a dipeptidyl peptidase IV inhibitor prevents 5-fluorouracil-induced reduction of small intestine weight. Eur J pharmacol 488:213-218, 2004

• 16) Yasuda N et al:Metformin Causes Reduction of Food Intake and Body Weight Gain and Improvement of Glucose Intolerance in Combination with Dipeptidyl Peptidase IV lnhibitor in Zucker fa/fa Rats. J Pharmacol Exp Ther 310:614-619, 2004

• 17) Landin K et al:Treating insulin resistance in hypertension with metformin reduces both blood pressure and metabolic risk factors. J Intern Med 229:181-187, 1991
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• 18) Landin K et al:Metformin and metoprolol CR treatment in non-obese men. J Intern Med 235:335-341, 1994

• 19) Giugliano D et al:Metformin improves glucose, lipid metabolism, and reduces blood pressure in hypertensive, obese women. Diabetes Care 16:1387-1390, 1993
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• 20) Velazquez EM et al:Metformin therapy in polycystic ovary syndrome reduces hyperinsulinemia, insulin resistance, hyperandrogenemia, and systolic blood pressure, while facilitating normal menses and pregnancy. Metabolism 43:647-654, 1994
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• 21) Dorella M et al:Improvement of insulin sensitivity by metformin treatnent does not lower blood pressure of nonobese insulin-resistant hypertensive patients with normal glucose tolerance. J Clin Endocrinol Metab 81:1568-1574, 1996

• 22) Snorgaard O et al:The effect of metformin on blood pressure and metabolism in nondiabetic hypertensive patients. J Intern Med 242:407-412, 1997
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• 23) Sundaresan P et al:Comparative effects of glibenclamide and metformin on ambulatory blood pressure and cardiovascular reactivity in NIDDM. Diabetes Care 20:692-697, 1997
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• 24) Verma S et al:Metformin decreases plasma insulin levels and systolic blood pressure in spontaneously hypertensive rats. Am J Physiol 267:H1250-1253, 1994
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• 25) Chen XL et al:Metformin relaxes rat tail artery by repolarization and resultant decreases in Ca2+ influx and intracellular [Ca2+]. J Hypertens 15:269-274, 1997
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• 26) Petersen JS et al:Acute sympathoinhibitory actions of metformin in spontaneously hypertensive rats. Hypertension 27:619-625, 1996
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• 27) Muntzel MS et al:Effects of adrenergic, cholinergic and ganglionic blockade on acute depressor responses to metformin in spontaneously hypertensive rats. J Pharmacol Exp Ther 281:618-623, 1997
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• 28) Tremoli E et al:Metformin reduces platelet hypersensitivity in hypercholesterolemic rabbits. Atherosclerosis 41:53-60, 1982
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• 29) De Caterina R et al:The direct effects of metformin on platelet function in Vitro. Eur J Clin Pharmacol 37:211-213, 1989
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• 30) Gin H et al:Study of the effect of metformin on platelet aggregation in insulin-dependent diabetics. Diabetes Res Clin Pract 6:61-67, 1989
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• 31) Gargiulo P et al:Metformin decreases platelet superoxide anion production in diabetic patients. Diabetes Metab Res Rev 18:156-159, 2002
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• 32) Verma S et al:Metfomiin treatment correctS vascular insulin resistance in hypertension. J Hypertens 18:1445-1450, 2000

• 33) Mather KJ et al:Improved endothelial function with metformin in type 2 diabetes mellitus. J Am Coll Cardiol 37:1344-1350, 2001
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P.89 掲載の参考文献

• 1) DeFronzo RA et al:Efficacy of metformin in patients with non-insulin-dependent diabetes mellitus. N Engl J Med 333:541-549, 1995
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• 2) UK Prospective Diabetes Study 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 352:837-853, 1998
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• 3) Stratton IM et al:Association of glycemia with macrovascular and microvascular complications of type 2 diabetes(UKPDS 35):prospective observational study. BMJ 321:405-412, 2000

• 4) Adler AI et al:Association of systolic blood pressure with macrovascular and microvascular complications of type 2 diabetes(UKPDS 36):prospective observational study. BMJ 321:412-419, 2000
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• 5) UK Prospective Diabetes Study Group:Effect of intensive glucose control with metformin on complication in overweight patients with type 2 diabetes (UKPDS 34) . Lancet 352:854-865, 1998

• 6) Katakami N et al:Metformin or gliclazide, rather than glibenclamide attenuates progression of carotid intima-media thickness in subjects with tye 2diabetes. Diabetologia 2004 in press

• 7) Abbasi F et al:Effect of metformin treatment on multiple cardiovascular disease risk factors in patients with type 2 diabetes mellitus. Metabolism 53: 159-164, 2004
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P.96 掲載の参考文献

• 1) King H et al:Global burden of diabetes, 1995-2025:prevalence, numerical estimates, and projections. Diabetes Care 21:1414-1431, 1998
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• 2) DeFronzo RA et al:Efficacy of metformin in patients with non-insulin-dependent diabetes mellitus. N Engl J Med 333:541-549, 1995
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• 3) UK 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 352:854-865, 1998
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• 4) Chiasson JL et al:Acarbose for prevention of type 2 diabetes mellitus:the STOP-NIDDM randomized trial. Lancet 359:2072-2077, 2002
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• 5) Diabetes Prevention Program Research Group:Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med, 346:393-403, 2002
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• 6) Fontbonne A et al:The effect of metformin on the metabolic abnormalities associated with upper-body fat distribution. Diabetes Care 19:920-926, 1996

P.101 掲載の参考文献

• 1) UKPDS Group:Intenslve blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet 352:837-853, 1998

• 2) UKPDS Group:Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes(UKPDS 34). Lancet 352:854-865, 1998
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• 3) Clarke P et al:Cost-effectiveness analysis of intensive blood-glucose control with metformin in overweight patients with type II diabetes(UKPDS No. 51). Diabetologia 44:298-304, 2001
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• 4) Briggs A et al:Handling uncertainty when performing economic evaluation of health care intervention. Health Technol Assess 3:1-134, 1999

• 5) Goldman L et al:27th Bethesda Conference:matching the intensity of risk factor management with the hazard for coronary disease events. Task Force 6:cost-effectiveness of assessment and management of risk factors. J Am Coll Cardiol 27:1020-1030, 1996
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• 6) UKPDS Group:Cost-effectiveness of an intensive blood glucose control policy in patients with type 2 diabetes:economic analysis alongside a randomized controlled trial. (UKPDS 41). BMJ 320:1373-1378, 2000
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• 7) Royal College of General Practitioners Effective Clinical Practice Unit:Clinical guidelines for type 2 diabetes:management of blood glucose. University of Sheffield 2002

• 8) Ward AJ et al:Health and economic impact of combining metformin with nateglinide to achieve glycemic control:Comparison of the lifetime costs of complications in the U.K. Cost Eff Resour Alloc 2:2, 2004

• 9) Neeser K et al:Cos-effectiveness of combination therapy with pioglitazone for type 2 diabetes mellitus from a German statutory healthcare perspective. Pharmacoeconomics 22:321-341, 2004

• 10) Tumer RC:The U. K. Prospective Diabetes Study. A review. Diabetes Care 21 Suppl 3:C35-C38, 1998

• 11) Bell DSH:Type 2 diabetes mellitus:What is the optimal treatment regimen? Am J Med 116:23S-29S, 2004

III. 症例に見るメトホルミンの効果的な使い方

P.107 掲載の参考文献

• 1) Lee A, Morley JE:Metformln decreases food consumption and mduces weight loss in subjects with obestity with type II non-insulin-dependent diabetes. Obes Res 6:47-53, 1998

• 2) Trischitta V et al:Comparison of combined therapies in treatment of secondary failure to glyburide. Diabetes Care 15:539-542, 1992
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• 3) UK Prospective Diabetes Study(UKPDS) Group. Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS34). Lancet 352:854-865, 1998
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P.111 掲載の参考文献

• 1) UKPDS Group:Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). Lancet 352:854-865, 1998
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• 2) Zhou G et al:Role of AMP-activated protein kinase in mechanism of metfomin action. J Clin Invest 108:1167-1174, 2001

• 3) Shimomura I et al:Decreased IRS-2 and increased SREBP-1c lead to mixed insulin resistance and sensitivity in livers of lipodystrophic and ob/ob mice. Mol Cell 6:77-86, 2000
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• 4) Musi N et al:Metformin increases AMP-activated protein kinase activity in skeletal muscle of subjects with type 2 diabetes. Diabetes 51:2074-2081, 2002
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• 5) DeFronzo RA et al:Efficacy of metformin in patients with non-insulin-dependent diabetes mellitus. The Multicenter Metformin Study Group. N Engl J Med 333:541-549, 1995

• 6) Abbasi F et al:Effect of metformin treatment on multiple cardiovascular disease risk factors in patients with type 2 diabetes mellitus. Metabolism 53:159-164, 2004
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• 7) Wulffele MG et al:The effect of metformin on blood pressure, plasma cholesterol and triglycerides in type 2 diabetes:a systematic review. J Intern Med 256:1-14, 2004
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• 8) Kirpichnikov D et al:Metfomin:an update. Review. Ann Intern Med 137:25-33, 2002

• 9) Cusi K et al:Metformin:a review of its metabolic effects. Diabetes Rev 6:89-131, 1998

P.115 掲載の参考文献

• 1) Altuntas Y et al Comparison of additional metformin or NPH insulin to mealtime insulin lispro therapy with mealtime human insulin therapy in secondary OAD failure. Diabetes Obes Metab 5:371-378, 2003
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• 2) Kokic S et al:Lispro insulin and metformin versus other combination in the diabetes mellitus type 2 management after secondary oral antidiabeic drug failure. Coll Antropol 27:181-187, 2003

• 3) Malone JK et al:Therapy after single oral agent failure:adding a second oral agent or an insulin mixture? Diabetes Res Clin Pract 62:187-195, 2003
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P.123 掲載の参考文献

• 1) Knowler WC et al:Diabetes Prevention Program Research Group:Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med 346:393-403, 2002
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• 2) Chiasson JL et al:The STOP-NIDDM Trial:an international study on the efficacy of an alpha-glucosidase inhibitor to prevent type 2 diabetes in a population with impaired glucose tolerance:rationale, design, and preliminary screening data. Study to Prevent Non-Insulin-Dependent Diabetes Mellitus. Diabetes Care 21:1720-1725, 1998

• 3) 片平 宏, 石田 均:α-グルコシダーゼ阻害薬の適応症例の選択と使用法ならびに副作用とその対策. 日本臨牀 60 増刊 9:399-408, 2002

• 4) Coniff RF et al:Reduction of glycosylated hemoglobin and postprandial hyperglycemia by acarbose in patients with NIDDM. A placebo-controlled dose-comparison study. Diabetes Care 18:817-824, 1995
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• 5) 河盛隆造ほか:糖質水解酵素阻害剤の追加療法がSU剤治療NIDDMの血糖管理に与える影響. 糖尿病 39:527-536, 1996

• 6) 飯島敏彦ほか:インスリン非依存型糖尿病患者に対するα-グルコシダーゼ阻害薬 (ボグリボース) とスルフォニル尿素薬との併用療法 特にSU剤の減量効果の検討. 薬理と治療 25:841-849, 1997

• 7) Holman RR et al:A randomized double-blind trial of acarbose in type 2 diabetes shows improved glycemic control over 3 years (U. K. Prospective Diabetes Study 44). Diabetes Care 22:960-964, 1999

• 8) Shinozaki K et al:Improvement of insulin sensitivity and dyslipidemia with a new alpha-glucosidase inhibitor, voglibose, in nondiabetic hyperinsulinemic subjects. Metabolism 45:731-737, 1996
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• 9) Zhou G et al:Role of AMP-activated protein kinase in mechanism of metformin action. J Clin Invest 108:1167-1174, 2001
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• 10) Hundal RS, Inzucchi SE:Metformin:new understandings, new uses. Drugs 63:1879-1894, 2003
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• 11) UK 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 352:854-865, 1998
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• 12) Phillips P et al:Acarbose improves glycemic control in overweight type 2 diabetic patients insufficiently treated with metformin. Diabetes Care 26:269-273, 2003
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• 13) Halimi S et al:Efficacy and safety of acarbose add-on therapy in the treatment of overweight patients with Type 2 diabetes inadequately controlled with metformin:a double-blind, placebo-controlled study. Diabetes Res Clin Pract 50:49-56, 2000

• 14) Chiasson JL et al:Miglitol Canadian University Investigator Group:The synergistic effect of miglitol plus metformin combination therapy in the treatment of type 2 diabetes. Diabetes Care 24:989-994, 2001

P.126 掲載の参考文献

• 1) 日本糖尿病学会編:科学的根拠に基づく糖尿病診療ガイドライン2004, 南江堂, 東京, 2004

• 2) Kirpichnikov D:Metformin:An update. Ann Intern Med 137:25-33, 2002
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• 3) Inzucchi SE et al:Efficacy and metabolic effects of metformin and troglitazone in type II diabetes mellitus. N Engl J Med 338(13):867-872, 1998
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• 4) 林 洋一ほか:インスリン抵抗性が考えられる2型糖尿病での塩酸メトホルミンとチアゾリジン誘導体との併用効果. 糖尿病 45(S2):S148, 2002

• 5) Belcher G:Tolerability profile of Pioglitazone in combination with a Sulfonylurea or Metformin in controlled clinical trials. Diabetes 50(S12):416, 2001
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P.129 掲載の参考文献

• 1) UK Prospective Diabetes Study(UKPDS) Group-Effect of Intenslve blood-glucose control with metformin on complications in overweight patients with type 2 diabetes(UKPDS 34). Lancet 352:854-865, 1998
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• 2) 福田 元ほか:ナテグリニド投与における糖尿病患者の体重変化. Prog Med (JPN)21(9):2255-2258, 2001

P.133 掲載の参考文献

• 1) Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes(UKPDS 34) UK Prospective Diabetes Study(UKPDS) Group. Lancet 352:854-865, 1998
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• 2) Arslanian SA et al:Metformin therapy in obese adolescents with polycystic ovary syndrome and impaired glucose tolerance:amelioration of exaggerated adrenal response to adrenocorticotropin with reduction of insulinemia/insulin resistance. J Clin Endocrinol Metab 87:1555-1559, 2002
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• 3) Morin-Papunen L et al:Metformin reduces serum C-reactive protein levels in women with polycystic ovary syndrome, J Clin Endocrinol Metab 88:4649-4654, 2003

• 4) Jones KL et al:Effect of metfomin in pediatric patients with type 2 diabetes:a randomized controlled trial. Diabetes Care 25:89-94, 2002

• 5) Haas DA et al:Effects of metformin on body mass index, menstrual cyclicity, and ovulation induction in women with polycystic ovary syndrome. Fertility & Sterility 79:469-481, 2003
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• 6) Hale TW et al:Transfer of metformin into human milk. Diabetologia 45:1509-1514, 2002
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• 7) Meadows M:Pregnancy and the drug dilemma. FDA Consumer 35:16-20, 2001
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• 8) Jakubowicz DJ et al:Effects of metformin on early pregnancy loss in the polycystic ovary syndrome. J Clin Endocrinol Metab 87:524-529, 2002
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• 9) Salpeter SR et al:Risk of fatal and nonfatal lactic acidosis with metformin use in type 2 diabetes mellitus:systematic review and meta-analysis. Arch Intern Med 163:2594-2602, 2003
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• 10) Clarke P et al(Study UGUKPD):Cost-effectiveness analysis of intensive blood-glucose control with metformin in overweight patients with type II diabetes(UKPDS No. 51). Diabetologia 44:298-304, 2001
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• 11) Diabetes Prevention Program Research G:Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med 346:393-403, 2002
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• 12) Pasquali R et al:Effect of long-term treatment with metformin added to hypocaloric diet on body composition, fat distribution, and androgen and insulin levels in abdominally obese women with and without the polycystic ovary syndrome. J Clin Endocrinol Metab 85:2767-2774, 2000
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P.137 掲載の参考文献

• 1) Yki-Jarvinen H:Combination therapies with insulin in type 2 diabetes. Diabetes Care 24:758-767, 2001
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• 2) Clarke P et al:Cost-effectiveness analysis of intensive blood-glucose control with metformin in overweight patients with type II diabetes(UKPDS No. 51). Diabetologia 44:298-304, 2001
  pubmed

• 3) Lee A et al:Metformin decreases food consumption and induces weight loss in subjects with obesity with type II non-insulin-dependent diabetes. Obes Res 6:47-53, 1998
  pubmed

• 4) Bailey CJ et al:Metformin. N Engl J Med 334:574-579, 1996
  pubmed

• 5) UK 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 352:854-865, 1998
  pubmed

• 6) 清水弘行ほか:2型糖尿病症例への塩酸メトフォルミン治療による体重変動への 影響. Prog Med 22:450-453, 2002
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• 7) Nagasaka S et al:Comparison of pioglitazone and metformin efficacy using homeostasis model assessment. Diabetic Medicine 21:136-141, 2004
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• 8) Matsumoto K et al:Metformin attenuates progression of carotid arterial wall thickness in patients with type 2 diabetes. Diabetes Res Clin Pract 64:225-228, 2004
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• 9) 片上直人ほか:頸動脈エコーを用いたメトホルミンの動脈硬化進展抑制効果の検討. Prog Med 23:3038-3043, 2003
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IV. メトホルミンを使ってはいけない禁忌症例

P.145 掲載の参考文献

• 1) Misbin RI et al:Lactic acidosis in patients with diabetes treated with metformin. N Engl J Med 338:265-266, 1998
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• 2) Stades AM et al:Metformin and lactic acidosis:cause or coincidence? A review of case reports. J Intern Med 255:179-187, 2004

• 3) Marchesini G et al:Metformin in non-alcoholic steatohepatitis. Lancet 358:893-894, 2001
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V. メトホルミンの副作用と服薬指導での注意点

P.151 掲載の参考文献

• 1) DeFronzo RA, Goodman AN and the Multicenter Metformin Study Group:Efficacy of metformin in patients with non-insulin-dependent diabetes mellitus. N Engl J Med 333:541-549, 1995

• 2) UK Prospective Diabetes Study(UKPDS) Group:Effect of intensive blood glucose control with metformin on complications in overweight patients with diabetes (UKPDS 34). Lancet 352:854-865, 1998
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• 3) Diabetes Prevention Program Research Group:Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med 346:393-403, 2002
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• 4) Bailey CJ:Biguanide and NIDDM. Diabetes Care 15:744-772, 1992

• 5) Bailey CJ:Metformin reVisted:Its actions and indications for use. Diabetic Med 5:315-320, 1988

• 6) Stang M et al:Incidence of lactic acidosis in metformin users. Diabetes Care 22:925-927, 1999
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• 7) Misbin RI et al:Lactic acidosis in patients with diabetes treated with metformin. N Engl J Med 338:265-266, 1998
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• 8) Bailey CJ et al:Drug Therapy, metformin. N Engl J Med 333:574-579, 1995

• 9) Cusi K et al:Metformin:a review of its metabolic effects. Diabetes Rev 6:89-131, 1998

• 10) Garber AJ et al:Efficacy of metformin in type 2 diabetes:results of a double-blind, placebo-controlled, dose-response trial. Am J Med 102:491-497, 1997

• 11) Bytzer P et al:Oral hypoglycaemic drugs and gastrointestinal symptoms in diabetes mellitus. Aliment Pharmacol Ther 15:137-142, 2001
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