, Volume 54, Issue 3, pp 355–368 | Cite as

Drug Treatment of Non-Insulin-Dependent Diabetes Mellitus in the 1990s

Achievements and Future Developments
  • André J. Scheen
Leading Article


Non-insulin-dependent diabetes mellitus (NIDDM, type 2 diabetes) is a heterogeneous disease resulting from a dynamic interaction between defects in insulin secretion and insulin action. There are various pharmacological approaches to improving glucose homeostasis, but those currently used in clinical practice either do not succeed in restoring normoglycaemia in most patients or fail after a variable period of time.

For glycaemic regulation, 4 classes of drugs are currently available: sulphonylureas, biguanides (metformin), α-glucosidase inhibitors (acarbose) and insulin, each of which has a different mode and site of action. These standard pharmacological treatments may be used individually for certain types of patients, or may be combined in a stepwise fashion to provide more ideal glycaemic control for most patients.

Adjunct treatments comprise a few pharmacological approaches which may help to improve glycaemic control by correcting some abnormalities frequently associated with NIDDM, such as obesity (serotoninergic anorectic agents) and hyperlipidaemia (benfluorex).

There is intensive pharmaceutical research to find new drugs able to stimulate insulin secretion (new sulphonylurea or nonsulphonylurea derivatives, glucagonlike peptide-1), improve insulin action (thiazolidinediones, lipid interfering agents, glucagon antagonists, vanadium compounds) or reduce carbohydrate absorption (miglitol, amylin analogues, glucagon-like peptide-1). Further studies should demonstrate the superiority of these new compounds over the standard antidiabetic agents as well as their optimal mode of administration, alone or in combination with currently available drugs.


Metformin Acarbose Repaglinide Glimepiride Glipizide 
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  1. 1.
    Scheen AJ, Lefèbvre PJ. Pathophysiology of type 2 diabetes. In: Kuhlmann J, Puls W, editors. Handbook of experimental pharmacology: oral antidiabetics. Berlin: Springer Verlag, 1995:7–42Google Scholar
  2. 2.
    Lefèbvre PJ, Scheen AJ. Management of non-insulin-dependent diabetes mellitus. Drugs 1992; 44 Suppl. 3: 29–38PubMedGoogle Scholar
  3. 3.
    Williams G. Management of non-insulin-dependent diabetes mellitus. Lancet 1995; 343: 95–100Google Scholar
  4. 4.
    Lefèbvre PJ, Scheen AJ. Improving the action of insulin. Clin Invest Med 1995; 18: 340–7PubMedGoogle Scholar
  5. 5.
    Alberti KGMM, Gries FA, Jervell J, et al. A desktop guide for the management of non-insulin-dependent diabetes mellitus (NIDDM): an update. Diabetic Med 1994; 15: 899–909Google Scholar
  6. 6.
    American Diabetes Association. Consensus statement: the pharmacological treatment of hyperglycemia in NIDDM. Diabetes Care 1995; 18: 1510–8Google Scholar
  7. 7.
    Gerich JE. Oral hypoglycemic agents. N Engl J Med 1989; 321: 1231–45PubMedGoogle Scholar
  8. 8.
    Kuhlmann J, Puls W, editors. Oral antidiabetics. In: Handbook of experimental pharmacology. Berlin: Springer Verlag, 1995Google Scholar
  9. 9.
    United Kingdom Prospective Diabetes Study Group. United Kingdom Prospective Diabetes Study Group (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 1995; 310: 83–8Google Scholar
  10. 10.
    United Kingdom Prospective Diabetes Study Group. UK Prospective Diabetes Study 16: overview of 6 years’ therapy of type II diabetes, a progressive disease. Diabetes 1995; 44: 1249–58Google Scholar
  11. 11.
    Melander A, Bitzen P-O, Faber O, et al. Sulphonylurea anti-diabetic drugs: an update of their clinical pharmacology and rational therapeutic use. Drugs 1989; 37: 58–72PubMedGoogle Scholar
  12. 12.
    Groop LC. Sulfonylureas and NIDDM. Diabetes Care 1992; 15: 737–54PubMedGoogle Scholar
  13. 13.
    Lebovitz HE, Melander A. Sulfonylureas: basic aspects and clinical uses. In: Alberti KGMM, DeFronzo RA, Keen H, et al., editors. International textbook of diabetes mellitus. Chichester: J Wiley, 1992: 745–72Google Scholar
  14. 14.
    Beck-Nielsen H, Hother-Nielsen O, Pedersen P. Mechanism of action of sulfonylureas with special reference to the extrapancreatic effect: an overview. Diabetic Med 1988; 5: 613–20PubMedGoogle Scholar
  15. 15.
    Pontiroli AE, Calderara A, Pozza G. Secondary failure of oral hypoglycaemic agents: frequency, possible causes, and management. Diabetes Metab Rev 1994; 10: 31–43PubMedGoogle Scholar
  16. 16.
    Berelowitz M, Fischette C, Cefalu W, et al. Comparative efficacy of a once-daily controlled-released formulation of glipizide and immediate-release glipizide in patients with NIDDM. Diabetes Care 1994; 17: 1460–4PubMedGoogle Scholar
  17. 17.
    Simonson DC, Kourides IA, Feinglos M, et al. Efficacy, safety, and dose-response characteristics of glipizide gastrointestinal therapeutic system on glycemic control and insulin secretion in NIDDM: results of two multicenter, randomized, placebo-controlled clinical trials. Diabetes Care 1997; 20: 597–606PubMedGoogle Scholar
  18. 18.
    Peters AL, Davidson MB. Maximal dose glyburide therapy in markedly symptomatic patients with type 2 diabetes: a new use for an old friend. J Clin Endocrinol Metab 1996; 81: 2423–7PubMedGoogle Scholar
  19. 19.
    Melander A. Oral antidiabetic drugs: an overview. Diabetic Med 1996; 13 Suppl. 6: S143–7PubMedGoogle Scholar
  20. 20.
    Campbell IW. Hypoglycemia and type II diabetes: sulfonylureas. In: Frier B, Fisher M, editors. Hypoglycemia and diabetes: clinical and physiological aspects. London: Edward Arnold, 1993: 387–92Google Scholar
  21. 21.
    Stahl M, Berger W. Sulfonylurées: pharmacologie et risque hypoglycémique. In: Journées de Diabétologie de l’Hôtel-Dieu. Paris: Flammarion Médecine-Sciences, 1995: 108–19Google Scholar
  22. 22.
    Scheen AJ, Lefèbvre PJ. Antihyperglycaemic agents: drug interactions of clinical importance. Drug Safety 1995; 12: 32–45PubMedGoogle Scholar
  23. 23.
    Smits P, Thien T. Cardiovascular effects of sulphonylurea derivatives: implications for the treatment of NIDDM? Diabetologia 1995; 38: 116–21PubMedGoogle Scholar
  24. 24.
    Leibowitz G, Cerasi E. Sulphonylurea treatment of NIDDM patients with cardiovascular disease: a mixed blessing? Diabetologia 1996; 39: 503–14PubMedGoogle Scholar
  25. 25.
    Bailey CJ. Biguanides and NIDDM. Diabetes Care 1992; 15: 755–72PubMedGoogle Scholar
  26. 26.
    Hermann LS, Melander A. Biguanides: basic aspects and clinical uses. In: Alberti KGMM, DeFronzo RA, Keen H, et al., editors. International textbook of diabetes mellitus. Chichester: J Wiley, 1992:773–95Google Scholar
  27. 27.
    Scheen AJ, Lefèbvre PJ. La metformine: des effets métaboliques aux indications thérapeutiques. Med Hyg 1993; 51: 1993–8Google Scholar
  28. 28.
    Dunn CJ, Peters DH. Metformin: a review of its pharmacological properties and therapeutic use in non-insulin-dependent diabetes mellitus. Drugs 1995; 49: 721–49PubMedGoogle Scholar
  29. 29.
    Bailey CJ, Turner RC. Metformin. N Engl J Med 1996; 334: 574–9PubMedGoogle Scholar
  30. 30.
    Andreani D, Lefèbvre P, editors. Metformin: mechanisms of action and clinical use. Diabetes Metab Rev 1995; 11 Suppl. 1: S1–108Google Scholar
  31. 31.
    DeFronzo RA, Goodman AM. Efficacy of metformin in patients with non-insulin-dependent diabetes mellitus: the Multicenter Metformin Study Group. N Engl J Med 1995; 333: 541–9PubMedGoogle Scholar
  32. 32.
    Sirtori CR, Pasik C. Re-evaluation of a biguanide, metformin: mechanism of action and tolerability. Pharmacol Research 1994; 30: 187–228Google Scholar
  33. 33.
    Scheen AJ. Clinical pharmacokinetics of metformin. Clin Pharmacokinet 1996; 30: 359–71PubMedGoogle Scholar
  34. 34.
    Gregorio F, Ambrosi F, Filipponi P, et al. Is metformin safe enough for ageing type 2 diabetic patients? Diabete Metab 1996; 22: 43–50PubMedGoogle Scholar
  35. 35.
    Lebovitz HE. Oral antidiabetic drugs: the emergence of alpha glucosidase inhibitors. Drugs 1992; 44 Suppl 3.: 21–8PubMedGoogle Scholar
  36. 36.
    Lefèbvre PJ, Standl E, editors. New aspects in diabetes: treatment strategies with alpha-glucosidase inhibitors. Berlin-New York: de Gruyter, 1992Google Scholar
  37. 37.
    Balfour JA, McTavish D. Acarbose: an update of its pharmacology and therapeutic use in diabetes mellitus. Drugs 1993; 46: 1025–54PubMedGoogle Scholar
  38. 38.
    Nieuwenhuijzen Kruseman AC, Sels JPJE, Wolffenbuttel BHR, editors. α-Glucosidase inhibitors in diabetes. Eur J Clin Invest 1994; 24 Suppl. 3: 1–54Google Scholar
  39. 39.
    Chiasson JL, Josse RG, Hunt JA, et al. The efficacy of acarbose in the treatment of patients with non-insulin-dependent diabetes mellitus: a multicenter controlled clinical trial. Ann Intern Med 1994; 121: 928–35PubMedGoogle Scholar
  40. 40.
    Coniff RF, Shapiro JA, Seaton TB. Long-term efficacy and safety of acarbose in the treatment of obese subjects with non-insulin-dependent diabetes mellitus. Arch Intern Med 1994; 154: 2442–8PubMedGoogle Scholar
  41. 41.
    Coniff RF, Shapiro JA, Seaton TB, et al. Multicenter, placebo-controlled trial comparing acarbose (BAY g 5421) with placebo, tolbutamide, and tolbutamide-plus-acarbose in non-insulin-dependent diabetes mellitus. Am J Med 1995; 98: 443–51PubMedGoogle Scholar
  42. 42.
    Holman RR, Cull CA, Turner RC. Glycaemic improvement over one year in a double-blind trial of acarbose in 1,946 NIDDM patients [abstract]. Diabetologia 1996; 39 Suppl 1.: A44Google Scholar
  43. 43.
    Turner RC, Holman RR. Insulin use in NIDDM: rationale based on pathophysiology of disease. Diabetes Care 1990; 13: 1011–20PubMedGoogle Scholar
  44. 44.
    Genuth S. Insulin use in NIDDM. Diabetes Care 1990; 13: 1240–64PubMedGoogle Scholar
  45. 45.
    Genuth S. Management of the adult onset diabetic with sulfonylurea drug failure. Endocrinol Metab Clin North Am 1992; 21: 351–70PubMedGoogle Scholar
  46. 46.
    Scheen AJ. Insulin therapy in the treatment of NIDDM. IDF Bull 1996; 41: 16–8Google Scholar
  47. 47.
    Colwell JA. DCCT findings — applicability and implications for NIDDM. Diabetes Rev 1994; 2: 277–91Google Scholar
  48. 48.
    Edelman SV, Henry RR. Insulin therapy for normalizing glycosylated hemoglobin in Type II diabetes. Diabetes Rev 1995; 3: 308–34Google Scholar
  49. 49.
    Colwell JA. The feasibility of intensive insulin management in non-insulin-dependent diabetes mellitus. Ann Intern Med 1996; 124: 131–5PubMedGoogle Scholar
  50. 50.
    Colwell JA. Should we use intensive insulin therapy after oral agent failure in type II diabetes? Diabetes Care 1996; 19: 896–8PubMedGoogle Scholar
  51. 51.
    Ohkubo Y, Kishikawa H, Araki E, et al. Intensive insulin therapy prevents the progression of diabetic microvascular complications in Japanese patients with non-insulin-dependent diabetes mellitus: a randomized prospective 6-year study. Diabetes Res Clin Pract 1995; 28: 103–17PubMedGoogle Scholar
  52. 52.
    Stout RW. Insulin and atheroma: 20-year perspective. Diabetes Care 1990; 13: 631–51PubMedGoogle Scholar
  53. 53.
    Malmberg K, DIGAMI Study Group. Randomized trial of insulin-glucose infusion followed by subcutaneous insulin treatment in diabetic patients with acute myocardial infarction (DIGAMI study): effects on mortality at 1 year. J Am Coll Cardiol 1995; 26: 57–65PubMedGoogle Scholar
  54. 54.
    Lebovitz HE. Stepwise and combination drug therapy for the treatment of NIDDM. Diabetes Care 1994; 17: 1542–4PubMedGoogle Scholar
  55. 55.
    Hermann LS. Biguanides and sulfonylureas as combination therapy in NIDDM. Diabetes Care 1990; 13 Suppl 3.: 37–41PubMedGoogle Scholar
  56. 56.
    Scheen AJ, Castillo MJ, Lefèbvre PJ. Combination of oral anti-diabetic drugs and insulin in the treatment of non-insulin-dependent diabetes. Acta Clin Belg 1993; 48: 259–68PubMedGoogle Scholar
  57. 57.
    Johnson JL, Wolf SL, Kabadi UM. Efficacy of insulin and sulfonylurea combination therapy in type II diabetes: a meta-analysis of the randomized placebo-controlled trials. Arch Intern Med 1996; 156: 259–64PubMedGoogle Scholar
  58. 58.
    Scheen AJ, Lefèbvre PJ. Insulin versus insulin plus sulfonylureas in type 2 diabetic patients with secondary failure to sulfonylureas. Diabetes Res Clin Pract 1989; 6: S33–43PubMedGoogle Scholar
  59. 59.
    Castillo M, Scheen AJ, Paolisso G, et al. The addition of glipizide to insulin therapy in type-II diabetic patients with secondary failure to sulfonylureas is useful only in the presence of a significant residual insulin secretion. Acta Endocrinol 1987; 116: 364–72PubMedGoogle Scholar
  60. 60.
    Yki-Järvinen H, Kauppila M, Kujansuue E, et al. Comparison of insulin regimens in patients with non-insulin-dependent diabetes mellitus. N Engl J Med 1992; 327: 1426–33PubMedGoogle Scholar
  61. 61.
    Golay A, Guillet-Dauphiné N, Fendel A, et al. The insulin-sparing effect of metformin in insulin-treated diabetic patients. Diabetes Metab Rev 1995; 11 Suppl. 1: S63–7PubMedGoogle Scholar
  62. 62.
    Giugliano D, Quatraro A, Consoli G, et al. Metformin for obese, insulin-treated diabetic patients: improvements in glycaemic control and reduction of metabolic risk factors. Eur J Clin Pharmacol 1993; 44: 107–12PubMedGoogle Scholar
  63. 63.
    Hotta N, Kakuta H, Koh N, et al. The effects of acarbose on blood glucose profiles of type 2 diabetic patients receiving insulin therapy. Diabetic Med 1993; 10: 355–8PubMedGoogle Scholar
  64. 64.
    Coniff RF, Shapiro JA, Seaton TB, et al. A double-blind placebo-controlled trial evaluating the safety and efficacy of acarbose for the treatment of patients with insulin-requiring type II diabetes. Diabetes Care 1995; 18: 928–32PubMedGoogle Scholar
  65. 65.
    Van der Wal PS, Scheen A, Van Gaal L, et al. Efficacy of bedtime NPH insulin alone as compared to combination with metformin and/or glipizide in NIDDM patients with secondary failure to oral hypoglycemic agents [abstract]. Diabetes 1996; 45 Suppl. 2: 286AGoogle Scholar
  66. 66.
    Pi-Sunyer FX. Weight and non-insulin-dependent diabetes mellitus. Am J Clin Nutr 1996; 63 Suppl.: 426S–9SPubMedGoogle Scholar
  67. 67.
    Scheen AJ, Lefèbvre PJ. Pharmacological treatment of the obese diabetic patient. Diabète Metab 1993; 19: 547–59PubMedGoogle Scholar
  68. 68.
    Arnaud O, Nathan C. Antiobesity and lipid-lowering agents with antidiabetic activity. In: Bailey CJ, Flatt PR, editors. New antidiabetic drugs. Nishimura: Smith-Gordon, 1990: 133–42Google Scholar
  69. 69.
    Bray GA, Ryan DH. Drugs used in the treatment of obesity. Diabetes Rev 1997; 5: 83–103Google Scholar
  70. 70.
    Davis R, Faulds D. Dexfenfluramine: an updated review of its therapeutic use in the management of obesity. Drugs 1996; 52: 696–724PubMedGoogle Scholar
  71. 71.
    Guy-Grand B. Clinical studies with dexfenfluramine: from past to future. Obesity Res 1995; 3 Suppl. 4: 491S–6SGoogle Scholar
  72. 72.
    O’Kane M, Wiles PG, Wales JK. Fluoxetine in the treatment of obese type 2 diabetic patients. Diabetic Med 1994; 11: 105–10PubMedGoogle Scholar
  73. 73.
    Scheen AJ, Paolisso G, Salvatore T, et al. Improvement of insulin-induced glucose disposal in obese patients with NIDDM after 1-wk treatment with d-fenfluramine. Diabetes Care 1991; 14: 325–32PubMedGoogle Scholar
  74. 74.
    Maheux P, Ducros F, Bourque J, et al. Fluoxetine improves insulin sensitivity in obese patients with non-insulin-dependent diabetes mellitus independently of weight loss. Int J Obesity 1997; 21: 97–102Google Scholar
  75. 75.
    Scheen AJ. Antiobesity drugs in the management of diabetes. Int Diabetes Monit 1997; 9(1): 1–8Google Scholar
  76. 76.
    Kosmiski L, Eckel RH. Anorectic agents in non-insulin dependent diabetes mellitus. Curr Opin Endocrinol Diabetes 1997; 4: 36–9Google Scholar
  77. 77.
    Reaven GM, editor. Insulin resistance, hyperinsulinemia and diabetes: contribution of benfluorex. Diabetes Metab Rev 1993; 9 Suppl. 1: S1–S72Google Scholar
  78. 78.
    Giustina A, Rocca I, Romanelli G, et al. Effects of benfluorex on glucose tolerance, metabolic control, beta-cell secretion, and peripheral sensitivity to insulin in obese type II diabetic patients on a body weight-maintaining diet. Curr Ther Res 1989; 45: 33–42Google Scholar
  79. 79.
    Cavallo-Perin P, Estivi P, Boine L, et al. Benfluorex and blood glucose control in non-insulin-dependent diabetic patients. J Endocrinol Invest 1991; 14: 109–13PubMedGoogle Scholar
  80. 80.
    Bianchi R, Bongers V, Bravenboer B, et al. Effects of benfluorex on insulin resistance and lipid metabolism in obese type II diabetic patients. Diabetes Care 1993; 16: 557–9PubMedGoogle Scholar
  81. 81.
    Pontiroli AE, Pacchioni M, Piatti PM, et al. Benfluorex in obese noninsulin dependent diabetes mellitus patients poorly controlled by insulin: a double blind study versus placebo. J Clin Endocrinol Metab 1996; 81: 3727–32PubMedGoogle Scholar
  82. 82.
    Bailey CJ, Flatt PR, editors. New antidiabetic drugs. Nishimura: Smith-Gordon, 1990Google Scholar
  83. 83.
    Bressler R, Johnson D. New pharmacological approaches to therapy of NIDDM. Diabetes Care 1992; 15: 792–805PubMedGoogle Scholar
  84. 84.
    Rachman J, Turner RC. Drugs on the horizon for treatment of type 2 diabetes. Diabetic Med 1995; 12: 467–78PubMedGoogle Scholar
  85. 85.
    Wolffenbuttel BHR, Graal MB. New treatments for patients with type 2 diabetes mellitus. Postgrad Med J 1996; 72: 657–62PubMedGoogle Scholar
  86. 86.
    Turner RC, editor. New oral antidiabetic agents: from today to tomorrow. Diab Res Clin Pract 1995; 28 Suppl.: S1–208Google Scholar
  87. 87.
    Bischoff H, Lebovitz HE. Oral antidiabetic drugs in research and development. In: Kuhlmann J, Puls W, editors. Handbook of experimental pharmacology: oral antidiabetics. Berlin: Springer Verlag, 1995: 651–96Google Scholar
  88. 88.
    Matthews DR, Riddle MC, editors. Proceedings of the International Glimepiride Symposium. Hormone Metab Res 1995; 28: 403–526Google Scholar
  89. 89.
    Goldberg RB, Holvey SM, Schneider J, et al. A dose-response study of glimepiride in patients with NIDDM who have previously received sulfonylurea agents. Diabetes Care 1996; 19: 849–56PubMedGoogle Scholar
  90. 90.
    Rosenstock J, Samols E, Muchmore DB, et al. Glimepiride, a new once-daily sulfonylurea: a double-blind placebo-controlled study of NIDDM patients. Diabetes Care 1996; 19: 1194–9PubMedGoogle Scholar
  91. 91.
    Malaisse WJ. Stimulation of insulin release by non-sulfonylurea hypoglycemic agents: the meglitinide family. Horm Metab Res 1995; 27: 263–6PubMedGoogle Scholar
  92. 92.
    Wolffenbuttel BHR, Nijst L, Sels JPJE, et al. Effects of a new oral hypoglycaemic agent, repaglinide, on metabolic control in sulphonylurea-treated patients with NIDDM. Eur J Clin Pharmacol 1993; 45: 113–6PubMedGoogle Scholar
  93. 93.
    Kikuchi M. Modulation of insulin secretion in non-insulin-dependent diabetes mellitus by two novel oral hypoglycaemic agents, NN623 and A 4166. Diabetic Med 1996; 13 Suppl. 6: S151–5PubMedGoogle Scholar
  94. 94.
    Skillman CA, Raskin P. A double-masked placebo-controlled trial assessing effects of various doses of BTS 67 582, a novel insulinotropic agent, on fasting hyperglycemia in NIDDM patients. Diabetes Care 1997; 20: 591–6PubMedGoogle Scholar
  95. 95.
    Robertson RP, Halter JB, Porte D. A role for alpha-adrenergic receptors in abnormal insulin secretion in diabetes mellitus. J Clin Invest 1976; 57: 791–5PubMedGoogle Scholar
  96. 96.
    Broadstone VL, Pfeifer MA, Bajaj V, et al. α-Adrenergic blockade improves glucose-potentiated insulin secretion in non-insulin-dependent diabetes mellitus. Diabetes 1987; 36: 932–7PubMedGoogle Scholar
  97. 97.
    Zaitsev SV, Efanov AM, Efanova IB, et al. Imidazoline compounds stimulate insulin release by inhibition of KATP channels and interaction with the exocytotic machinery. Diabetes 1996; 45: 1610–8PubMedGoogle Scholar
  98. 98.
    Hoist JJ, Nauck MA, Deacon CF, et al. Potential of GLP-1 in diabetes management. In: Lefèbvre PJ, editor. Handbook of experimental pharmacology: glucagon III. Vol. 123. Berlin: Springer Verlag, 1996: 311–26Google Scholar
  99. 99.
    Holst JJ. GLP-1 in NIDDM. Diabetic Med 1996; 13 Suppl. 6: S156–60PubMedGoogle Scholar
  100. 100.
    Gutniak M, Orskov C, Holst JJ, et al. Antidiabetogenic effect of glucagon-like peptide-1 (7-36) amide in normal subjects and patients with diabetes mellitus. N Engl J Med 1992; 326: 1316–22PubMedGoogle Scholar
  101. 101.
    Nauck MA, Kleine N, Orskov C, et al. Normalization of fasting hyperglycaemia by exogenous glucagon-like peptide 1 (7-36amide) in type 2 (non-insulin-dependent) diabetic patients. Diabetologia 1993; 36: 741–4PubMedGoogle Scholar
  102. 102.
    Gutniak MK, Linde B, Hoist JJ, et al. Subcutaneous injection of the incretin hormone glucagon-like peptide 1 abolishes postprandial glycemia in non-insulin dependent diabetes. Diabetes Care 1994; 17: 1039–44PubMedGoogle Scholar
  103. 103.
    Willms B, Werner J, Hoist JJ, et al. Gastric emptying, glucose responses, and insulin secretion after liquid test meal: effects of exogenous glucagon-like peptide-1 (GLP-1)-(7-36)amide in type 2 (noninsulin-dependent) diabetic patients. J Clin Endocrinol Metab 1996; 81: 327–32PubMedGoogle Scholar
  104. 104.
    Juntti-Berggren L, Pigon J, Karpe F, et al. The antidiabetogenic effect of GLP-1 is maintained during a 7-day treatment period and improves diabetic dyslipoproteinemia in NIDDM patients. Diabetes Care 1996; 19: 1200–6PubMedGoogle Scholar
  105. 105.
    Gutniak MK, Larsson H, Heiber SJ, et al. Potential therapeutic levels of glucagon-like peptide 1 achieved in humans by a buccal tablet. Diabetes Care 1996; 19: 843–8PubMedGoogle Scholar
  106. 106.
    Gutniak M, Larsson H, Sanders S, et al. GLP-1 tablet, a new therapeutic alternative for NIDDM [abstract]. Diabetologia 1996; 39 Suppl. 1: A43Google Scholar
  107. 107.
    Hofmann CA, Colca JR. New oral thiazolidinedione antidiabetic agents act as insulin sensitizers. Diabetes Care 1992; 15: 1075–8PubMedGoogle Scholar
  108. 108.
    Saltiel AR, Olefsky JM. Thiazolidinediones in the treatment of insulin resistance and type II diabetes. Diabetes 1996; 45: 1661–9PubMedGoogle Scholar
  109. 109.
    Willson TM, Cobb JE, Cowan DJ, et al. The structure-activity relationship between peroxisome proliferator-activated receptor gamma agonism and the antihyperglycemic activity of thiazolidinediones. J Med Chem 1996; 39: 665–8PubMedGoogle Scholar
  110. 110.
    Chaiken RL, Eckert-Norton M, Pasmantier R, et al. Metabolic effects of darglitazone, an insulin sensitizer, in NIDDM subjects. Diabetologia 1995; 38: 1307–12PubMedGoogle Scholar
  111. 111.
    Nolan JJ, Ludvik B, Beerdsen P, et al. Improvement in glucose tolerance and insulin resistance in obese subjects treated with troglitazone. N Engl J Med 1994; 331: 1188–93PubMedGoogle Scholar
  112. 112.
    Suter SL, Nolan JJ, Wallace P, et al. Metabolic effects of new oral hypoglycemic agent CS-045 in NIDDM subjects. Diabetes Care 1992; 15: 193–203PubMedGoogle Scholar
  113. 113.
    Mimura K, Umeda F, Hiramatsu S, et al. Effects of a new oral hypoglycaemic agent (CS-045) on metabolic abnormalities and insulin resistance in type 2 diabetes. Diabetic Med 1994; 11: 685–91PubMedGoogle Scholar
  114. 114.
    Kumar S, Boulton AJM, Beck-Nielsen H, et al. Troglitazone, an insulin action enhancer, improves metabolic control in NIDDM patients. Diabetologia 1996; 39: 701–9PubMedGoogle Scholar
  115. 115.
    Iwamoto Y, Kosaka K, Kuzuya T, et al. Effects of troglitazone, a new hypoglycemic agent, in patients with NIDDM poorly controlled by diet therapy. Diabetes Care 1996; 19: 151–6PubMedGoogle Scholar
  116. 116.
    Reaven GM. The fourth musketeer: from Alexandre Dumas to Claude Bernard. Diabetologia 1995, 38: 3–13PubMedGoogle Scholar
  117. 117.
    Boden G. Role of fatty acids in the pathogenesis of insulin resistance and NIDDM. Diabetes 1997; 45: 3–10Google Scholar
  118. 118.
    Fulcher GR, Alberti KGMM. Hypoglycaemic action of anti-lipolytic agents. In: Bailey CJ, Flatt PR, editors. New anti-diabetic drugs. Nishimura: Smith-Gordon, 1990: 143–55Google Scholar
  119. 119.
    Fulcher GR, Walker M, Catalano C, et al. Metabolic effects of suppression of nonesterified fatty acid levels with acipimox in obese NIDDM subjects. Diabetes 1992; 41: 1400–8PubMedGoogle Scholar
  120. 120.
    Vaag AA, Beck-Nielsen H. Effects of prolonged acipimox treatment on glucose and lipid metabolism and on in vivo insulin sensitivity in patients with non-insulin dependent diabetes mellitus. Acta Endocrinol 1992; 127: 344–50PubMedGoogle Scholar
  121. 121.
    Dean JD, McCarthy S, Betteridge DJ, et al. The effect of acipimox on non-insulin-dependent diabetic patients with persistent hyperlipidaemia. Diabetic Med 1993; 9: 611–5Google Scholar
  122. 122.
    Saloranta C, Taskinen M-R, Widen E, et al. Metabolic consequences of sustained suppression of free fatty acids by acipimox in patients with NIDDM. Diabetes 1993; 42: 1559–66PubMedGoogle Scholar
  123. 123.
    Foley JE. Rationale and application of fatty acid oxidation inhibitors in treatment of diabetes mellitus. Diabetes Care 1992; 15: 773–84PubMedGoogle Scholar
  124. 124.
    Wolf HPO. Possible new therapeutic approach in diabetes mellitus by inhibition of carnitine palmitoyltransferase 1 (CPT1). Horm Metabol Res 1992; Suppl. 26: 62–7Google Scholar
  125. 125.
    Ratheiser K, Schneeweiss B, Waldhäusl W, et al. Inhibition by etomoxir of carnitine palmitoyltransferase I reduces hepatic glucose production and plasma lipids in non-insulin-dependent diabetes mellitus. Metabolism 1991; 40: 1185–90PubMedGoogle Scholar
  126. 126.
    Hübinger A, Weikert G, Wolf HPO, et al. The effect of etomoxir on insulin sensitivity in type 2 diabetic patients. Horm Metabol Res 1992; 24: 115–8Google Scholar
  127. 127.
    Lefèbvre P, Paolisso G, Scheen A. The role of glucagon in non-insulin-dependent (type 2) diabetes mellitus. In: Sakamoto N, Angel A, Hotta H, editors. New directions in research and clinical works for obesity and diabetes mellitus. Excerpta Medica, 1991:25-9Google Scholar
  128. 128.
    Lefèbvre PJ. Glucagon and diabetes. In: Lefèbvre PJ, editor. Handbook of experimental pharmacology: glucagon IN. Vol. 123. Berlin: Springer Verlag, 1996: 115–31Google Scholar
  129. 129.
    Amatruda JM, Livingston JN. The search for glucagon antagonists. In: Lefèbvre PJ, editor. Handbook of experimental pharmacology: glucagon IN. Vol. 123. Berlin: Springer Verlag, 1996: 133–47Google Scholar
  130. 130.
    Shechter Y. Insulin-mimetic effects of vanadate: possible implications for future treatment of diabetes. Diabetes 1990; 39: 1–5PubMedGoogle Scholar
  131. 131.
    Goldfine AB, Simonson DC, Folli F, et al. Metabolic effects of sodium metavanadate in humans with insulin-dependent and noninsulin-dependent diabetes mellitus in vivo and in vitro studies. J Clin Endocrinol Metab 1995; 80: 3311–20PubMedGoogle Scholar
  132. 132.
    Cohen N, Halberstam M, Shlimovich P, et al. Oral vanadyl sulfate improves hepatic and peripheral insulin sensitivity in patients with non-insulin-dependent diabetes mellitus. J Clin Invest 1995; 95: 2501–9PubMedGoogle Scholar
  133. 133.
    Halberstam M, Cohen N, Shlimovich P, et al. Oral vanadyl sulfate improves insulin sensitivity in NIDDM but not in obese nondiabetic subjects. Diabetes 1996; 45: 659–66PubMedGoogle Scholar
  134. 134.
    Boden G, Chen X, Ruiz J, et al. Effects of vanadyl sulfate on carbohydrate and lipid metabolism in patients with noninsulin-dependent diabetes mellitus. Metabolism 1996; 45: 1130–5PubMedGoogle Scholar
  135. 135.
    Hotamisligil GS, Spiegelman BM. Tumor necrosis factor-α: a key component of the obesity-diabetes link. Diabetes 1994; 43: 1271–8PubMedGoogle Scholar
  136. 136.
    Hotamisligil GS, Peraldi P, Spiegelman BM. The molecular link between obesity and diabetes. Curr Opin Endocrinol Diab 1996; 3: 16–23Google Scholar
  137. 137.
    Ofei F, Hurel S, Newkirk J, et al. Effects of an engineered human anti-TNF-α antibody (CDP571) on insulin sensitivity and glycemic control in patients with NIDDM. Diabetes 1996; 45: 881–5PubMedGoogle Scholar
  138. 138.
    Scheen AJ, Castillo MJ, Paquot N, et al. No effect of neutralization of TNF-α on insulin-mediated glucose disposal in obese insulin-resistant subjects [abstract]. Diabetologia 1996; 39 Suppl. 1: A153Google Scholar
  139. 139.
    Workshop Proceedings. Gastrointestinal control of glycaemia. Diabetic Med 1996; 13 Suppl. 5: S1–S48Google Scholar
  140. 140.
    Johnson AB, Taylor R. Does suppression of postprandial blood glucose excursions by the α-glucosidase inhibitor miglitol improve insulin sensitivity in treated type II diabetic patients? Diabetes Care 1996; 19: 559–63PubMedGoogle Scholar
  141. 141.
    Kingma PJ, Menheere PPCA, Sels JP, et al. Alpha-glucosidase inhibition by miglitol in NIDDM patients. Diabetes Care 1992; 15: 478–83PubMedGoogle Scholar
  142. 142.
    Johnston PS, Coniff RF, Hoogwerf BJ, et al. Effects of the carbohydrase inhibitor miglitol in sulfonylurea-treated NIDDM patients. Diabetes Care 1994; 17: 20–9PubMedGoogle Scholar
  143. 143.
    Castillo MJ, Scheen AJ, Lefèbvre PJ. Amylin/islet amyloid polypeptide: biochemistry, physiology, patho-physiology. Diabete Metab 1995; 21: 3–25PubMedGoogle Scholar
  144. 144.
    Kolterman OG, Schwartz S, Coder C, et al. Effect of 14 days’ subcutaneous administration of the human amylin analogue, pramlintide (AC 137), on an intravenous insulin challenge and response to a standard liquid meal in patients with IDDM. Diabetologia 1996; 39: 492–9PubMedGoogle Scholar

Copyright information

© Adis International Limited 1997

Authors and Affiliations

  • André J. Scheen
    • 1
  1. 1.Department of MedicineDivision of Diabetes, Nutrition and Metabolic DisordersLiège 1Belgium

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