Drug Safety

, Volume 30, Issue 12, pp 1127–1142 | Cite as

Bodyweight Changes Associated with Antihyperglycaemic Agents in Type 2 Diabetes Mellitus

  • Kjeld HermansenEmail author
  • Lene S. Mortensen
Review Article


The majority of patients with type 2 diabetes mellitus are overweight or obese at the time of diagnosis, and obesity is a recognised risk factor for type 2 diabetes and coronary heart disease (CHD). Conversely, weight loss has been shown to improve glycaemic control in patients with type 2 diabetes, as well as to lower the risk of CHD. The traditional pharmacotherapies for type 2 diabetes can further increase weight and this may undermine the benefits of improved glycaemic control. Furthermore, patients’ desire to avoid weight gain may jeopardise compliance with treatment, thereby limiting treatment success and indirectly increasing the risk of long-term complications. This review evaluates the influences of established and emerging therapies on bodyweight in type 2 diabetes.


Metformin Rosiglitazone Pioglitazone Glycaemic Control Liraglutide 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



There are no relevant financial interests in this manuscript. Professor Hermansen has received honoraria as a member of advisory boards for Novo Nordisk A/S, Sanofi Aventis, Pfizer and Merck. Dr Mortensen has no conflicts of interest that are directly relevant to the content of this review article.

The authors would like to thank Dr Eva Cyhlarova and Dr Catherine Jones (Watermeadow Medical, Witney, UK) for their assistance in the preparation of this manuscript. This assitance was supported by a grant from Novo Nordisk A/S.


  1. 1.
    Wolf AM, Colditz GA. Current estimates of the economic cost of obesity in the United States. Obes Res 1998; 6(2): 173–5CrossRefGoogle Scholar
  2. 2.
    Tremble JM, Donaldson D. Is continued weight gain inevitable in type 2 diabetes mellitus? J R Soc Health 1999; 119(4): 235–9CrossRefGoogle Scholar
  3. 3.
    O’Keefe Jr JH, Miles JM, Harris WH, et al. Improving the adverse cardiovascular prognosis of type 2 diabetes. Mayo Clin Proc 1999; 74(2): 171–80PubMedCrossRefGoogle Scholar
  4. 4.
    Ridderstrale M, Gudbjornsdottir S, Eliasson B, et al. Steering Committee of the Swedish National Diabetes Register (NDR). Obesity and cardiovascular risk factors in type 2 diabetes: results from the Swedish National Diabetes Register. J Intern Med 2006; 259(3): 314–22PubMedCrossRefGoogle Scholar
  5. 5.
    Polonsky KS. Dynamics of insulin secretion in obesity and diabetes. Int J Obes Relat Metab Disord 2000; 24 Suppl. 2: S29–31PubMedCrossRefGoogle Scholar
  6. 6.
    Yki-Jarvinen H, Ryysy L, Kauppila M, et al. Effect of obesity on the response to insulin therapy in noninsulin-dependent diabetes mellitus. J Clin Endocrinol Metab 1997; 82(12): 4037–43PubMedCrossRefGoogle Scholar
  7. 7.
    Anderson JW, Konz EC. Obesity and disease management: effects of weight loss on comorbid conditions. Obes Res 2001; 9 Suppl. 4: 326–334SCrossRefGoogle Scholar
  8. 8.
    American Diabetes Association. Treatment of hypertension in diabetes [position statement]. Diabetes Care 1993; 16: 1394–401Google Scholar
  9. 9.
    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 1998; 352: 854–65CrossRefGoogle Scholar
  10. 10.
    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: 837–52CrossRefGoogle Scholar
  11. 11.
    Inzucchi SE. Oral antihyperglycemic therapy for type 2 diabetes: scientific review. JAMA 2002 Jan 16; 287(3): 360–72PubMedCrossRefGoogle Scholar
  12. 12.
    Laville M, Andreelli F. Mechanisms for weight gain during blood glucose normalization. Diabetes Metab 2000; 26 Suppl. 3: 42–5PubMedGoogle Scholar
  13. 13.
    Davies M. The reality of glycaemic control in insulin treated diabetes: defining the clinical challenges. Int J Obes 2004; 28 Suppl. 2: S14–22CrossRefGoogle Scholar
  14. 14.
    Korytkowski M. When oral agents fail: practical barriers to starting insulin. Int J Obes Relat Metab Disord 2002; 26 Suppl. 3: S18–24PubMedCrossRefGoogle Scholar
  15. 15.
    Heller S. Weight gain during insulin therapy in patients with type 2 diabetes mellitus. Diabetes Res Clin Pract 2004; 65 Suppl. 1: S23–7PubMedCrossRefGoogle Scholar
  16. 16.
    Wing R. Use of very-low-calorie diets in the treatment of obese persons with non-insulin-dependent diabetes mellitus. J Am Diet Assoc 1995; 95: 569–74PubMedCrossRefGoogle Scholar
  17. 17.
    Wing R, Marcus M, Blair EH, et al. Caloric restriction per se is a significant factor in improvements in glycemic control and insulin sensitivity during weight loss in obese NIDDM patients. Diabetes Care 1994; 17: 30–6PubMedCrossRefGoogle Scholar
  18. 18.
    Khan MA, St Peter JV, Breen GA, et al. Diabetes disease stage predicts weight loss outcomes with long-term appetite suppressants. Obes Res 2000; 8: 43–8PubMedCrossRefGoogle Scholar
  19. 19.
    Williamson DF, Thompson TJ, Thun M, et al. Intentional weight loss and mortality among overweight individuals with diabetes. Diabetes Care 2000; 23: 1499–504PubMedCrossRefGoogle Scholar
  20. 20.
    Anderson JW, Kendall CW, Jenkins DJ. Importance of weight management in type 2 diabetes: review with meta-analysis of clinical studies. J Am Coll Nutr 2003; 22: 331–9PubMedGoogle Scholar
  21. 21.
    Lean ME, Powrie JK, Anderson AS, et al. Obesity, weight loss and prognosis in type 2 diabetes. Diabet Med 1990; 7: 228–33PubMedCrossRefGoogle Scholar
  22. 22.
    Norris SL, Zhang X, Avenell A, et al. Efficacy of pharmacotherapy for weight loss in adults with type 2 diabetes mellitus: a meta-analysis. Arch Intern Med 2004; 164: 395–404CrossRefGoogle Scholar
  23. 23.
    Scheen AJ, Finer N, Hollander P, et al., for the RIO-Diabetes Study Group. Efficacy and tolerability of rimonabant in overweight or obese patients with type 2 diabetes: a randomised controlled study. Lancet 2006; 368: 1660–72PubMedCrossRefGoogle Scholar
  24. 24.
    DeFronzo RA. Pharmacologic therapy for type 2 diabetes mellitus. Ann Intern Med 1999 Aug 17; 131(4): 281–303PubMedGoogle Scholar
  25. 25.
    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. The Glipizide Gastrointestinal Therapeutic System Study Group. Diabetes Care 1997; 20(4): 597–606PubMedCrossRefGoogle Scholar
  26. 26.
    Bautista LJ, Bugos C, Dirnberger G, et al. Efficacy and safety profile of glimepiride in Mexican American Patients with type 2 diabetes mellitus: a randomized, placebo-controlled study. Clin Ther 2003; 25(1): 194–209CrossRefGoogle Scholar
  27. 27.
    Saloranta C, Hershon K, Ball M, et al. Efficacy and safety of nateglinide in type 2 diabetic patients with modest fasting hyperglycemia. J Clin Endocrinol Metab 2002; 87(9): 4171–6PubMedCrossRefGoogle Scholar
  28. 28.
    UK Prospective Diabetes Study (UKPDS). Relative efficacy of randomly allocated diet, sulphonylurea, insulin, or metformin in patients with newly diagnosed non-insulin dependent diabetes followed for three years. BMJ 1995 Jan 14; 310(6972): 83–8CrossRefGoogle Scholar
  29. 29.
    Campbell IW, Menzies DG, Chalmers J, et al. One year comparative trial of metformin and glipizide in type 2 diabetes mellitus. Diabet Metab 1994; 20(4): 394–400Google Scholar
  30. 30.
    Charpentier G, Fleury F, Kabir M, et al. Improved glycaemic control by addition of glimepiride to metformin monotherapy in type 2 diabetic patients. Diabet Med 2001; 18(10): 828–34PubMedCrossRefGoogle Scholar
  31. 31.
    Schernthaner G, Grimaldi A, Di Mario U, et al. GUIDE study: double-blind comparison of once-daily gliclazide MR and glimepiride in type 2 diabetic patients. Eur J Clin Invest 2004; 34: 535–42PubMedCrossRefGoogle Scholar
  32. 32.
    Rosenstock J, Hassman DR, Madder RD, et al. Repaglinide Versus Nateglinide Comparison Study Group. Repaglinide versus nateglinide monotherapy: a randomized, multicenter study. Diabetes Care 2004; 27(6): 1265–70PubMedCrossRefGoogle Scholar
  33. 33.
    Schernthaner G, Matthews DR, Charbonnel B, et al. Quartet [corrected] Study Group. Efficacy and safety of pioglitazone versus metformin in patients with type 2 diabetes mellitus: a double-blind, randomized trial. J Clin Endocrinol Metab 2004; 89(12): 6068–76PubMedCrossRefGoogle Scholar
  34. 34.
    Chiasson JL, Naditch L, Miglitol Canadian University Investigator Group. The synergistic effect of miglitol plus metformin combination therapy in the treatment of type 2 diabetes. Diabetes Care 2001; 24(6): 989–94PubMedCrossRefGoogle Scholar
  35. 35.
    Pavo I, Jermendy G, Varkonyi TT, et al. Effect of pioglitazone compared with metformin on glycemic control and indicators of insulin sensitivity in recently diagnosed patients with type 2 diabetes. J Clin Endocrinol Metab 2003; 88(4): 1637–45PubMedCrossRefGoogle Scholar
  36. 36.
    Hanefeld M, Brunetti P, Schernthaner GH, et al. 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 2004; 27(1): 141–7PubMedCrossRefGoogle Scholar
  37. 37.
    Charbonnel BH, Matthews DR, Schernthaner G, et al. QUARTET Study Group. A long-term comparison of pioglitazone and gliclazide in patients with type 2 diabetes mellitus: a randomized, double-blind, parallel-group comparison trial. Diabet Med 2005; 22(4): 399–405PubMedCrossRefGoogle Scholar
  38. 38.
    Belcher G, Lambert C, Edwards G, et al. Safety and tolerability of pioglitazones, metformin, and gliclazide in the treatment of type 2 diabetes. Diab Res Clin Pract 2005; 70: 53–62 1140CrossRefGoogle Scholar
  39. 39.
    Kendall DM, Rubin CJ, Mohideen P, et al. Improvement of glycemic control, triglycerides, and HDL cholesterol levels with muraglitazar a dual(a/g) peroxisome proliferator-activator, in patients with type 2 diabetes inadequately controlled with metformin monotherapy. Diabetes Care 2006; 29: 1016–23PubMedCrossRefGoogle Scholar
  40. 40.
    Goke B, German Pioglitazone Study Group. Improved glycemic control and lipid profile in a randomized study of pioglitazone compared with acarbose in patients with type 2 diabetes mellitus. Treat Endocrinol 2002; 1(5): 329–36PubMedCrossRefGoogle Scholar
  41. 41.
    Feinbock C, Luger A, Klingler A, et al. Austrian Glimepiride Study Group. Prospective multicentre trial comparing the efficacy of, and compliance with, glimepiride or acarbose treatment in patients with type 2 diabetes not controlled with diet alone. Diabetes Nutr Metab 2003; 16(4): 214–21PubMedGoogle Scholar
  42. 42.
    De Fine Olivarius N, Andreasen AH, Siersma V, et al. Changes in patient weight and the impact of antidiabetic therapy during the first 5 years after diagnosis of diabetes mellitus. Diabetologia 2006; 49: 2058–67PubMedCrossRefGoogle Scholar
  43. 43.
    Dornhorst A. Insulinotropic meglitinide analogues. Lancet 2001 Nov 17; 358(9294): 1709–16PubMedCrossRefGoogle Scholar
  44. 44.
    Raskin P, McGill J, Saad MF, et al. Repaglinide/Rosiglitazone Study Group. Combination therapy for type 2 diabetes: repaglinide plus rosiglitazone. Diabet Med 2004; 21(4): 329–35PubMedCrossRefGoogle Scholar
  45. 45.
    Del Prato S, Erkelens DW, Leutenegger M. Six-month efficacy of benfluorex vs. placebo or metformin in diet-failed type 2 diabetic patients. Acta Diabetol 2003; 40(1): 20–7PubMedCrossRefGoogle Scholar
  46. 46.
    Landgraf R, Frank M, Bauer C, et al. Prandial glucose regulation with repaglinide: its clinical and lifestyle impact in a large cohort of patients with type 2 diabetes. Int J Obes 2000; 24 Suppl. 3: S38–44CrossRefGoogle Scholar
  47. 47.
    Goldstein BJ, Pans M, Rubin CJ. Multicenter, randomized, double-masked, parallel-group assessment of simultaneous glipizide/metformin as second-line pharmacologic treatment for patients with type 2 diabetes mellitus that is inadequately controlled by a sulfonylurea. Clin Ther 2003; 25(3): 890–903PubMedCrossRefGoogle Scholar
  48. 48.
    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 Aug 31; 333(9): 541–9PubMedCrossRefGoogle Scholar
  49. 49.
    Kahn SE, Haffner SM, Heise MA, et al. ADOPT Study Group. Glycemic durability of rosiglitazone, metformin, or glyburide monotherapy. N Engl J Med 2006; 355(23): 2427–43PubMedCrossRefGoogle Scholar
  50. 50.
    UKPDS Group. Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). UK Prospective Diabetes Study. Lancet 1998; 12;352(9131): 854–65CrossRefGoogle Scholar
  51. 51.
    Mannucci E, Ognibene A, Cremasco F, et al. Effect of metformin on glucagon-like peptide 1 (GLP-1) and leptin levels in obese nondiabetic subjects. Diabetes Care 2001; 24: 489–94PubMedCrossRefGoogle Scholar
  52. 52.
    Yasuda N, Inoue T, Nagakura T, et al. Enhanced secretion of glucagon-like peptide 1 by biguanide compounds. Biochem Biophys Res Commun 2002; 15: 779–84CrossRefGoogle Scholar
  53. 53.
    Lindsay JR, Duffy NA, McKillop AM, et al. Inhibition of dipeptidyl peptidase IV activity by oral metformin in type 2 diabetes. Diabet Med 2005; 22: 654–7PubMedCrossRefGoogle Scholar
  54. 54.
    Lebovitz HE. Alpha-glucosidase inhibitors. Endocrinol Metab Clin North Am 1997 Sep; 26(3): 539–51PubMedCrossRefGoogle Scholar
  55. 55.
    van de Laar FA, Lucassen PL, Akkermans RP, et al. Alphaglucosidase inhibitors for patients with type 2 diabetes: results from a Cochrane systematic review and meta-analysis. Diabetes Care 2005; 28(1): 154–63PubMedCrossRefGoogle Scholar
  56. 56.
    Lindstrom J, Tuomilehto J, Spengler M. Acarbose treatment does not change the habitual diet of patients with type 2 diabetes mellitus. The Finnish Acargbos Study Group. Diabet Med 2000; 17(1): 20–5PubMedCrossRefGoogle Scholar
  57. 57.
    Fukase N, Takahashi H, Manaka H, et al. Differences in glucagon-like peptide-1 and GIP responses following sucrose ingestion. Diabetes Res Clin Pract 1992; 15(3): 187–95PubMedCrossRefGoogle Scholar
  58. 58.
    Miyazaki Y, Mahankali A, Matsuda M, et al. Effect of pioglitazone on abdominal fat distribution and insulin sensitivity in type 2 diabetic patients. J Clin Endocrinol Metab 2002; 87(6): 2784–91PubMedCrossRefGoogle Scholar
  59. 59.
    Dormandy JA, Charbonnel B, Eckland DJ, et al. PROACTIVE investigators. Secondary prevention of macrovascular events in patients with type 2 diabetes in the PROACTIVE Study (PROspective pioglitAzone Clinical Trial In macro Vascular Events): a randomised controlled trial. Lancet 2005 Oct 8; 366(9493): 1279–89PubMedCrossRefGoogle Scholar
  60. 60.
    Boden G, Zhang M. Recent findings concerning TZDs in the treatment of diabetes. Exp Opin Investig Drugs 2006; 15: 243–50CrossRefGoogle Scholar
  61. 61.
    Despres JP, Nadeau A, Tremblay A, et al. Role of deep abdominal fat in the association between regional adipose tissue distribution and glucose tolerance in obese women. Diabetes 1989; 38(3): 304–9PubMedCrossRefGoogle Scholar
  62. 62.
    Yamauchi T, Kamon J, Waki H, et al. The mechanisms by which both heterozygous peroxisome proliferator-activated receptor gamma (PPARgamma) deficiency and PPARgamma agonist improve insulin resistance. J Biol Chem 2001 Nov 2; 276(44): 41245–54PubMedCrossRefGoogle Scholar
  63. 63.
    Danforth Jr E. Failure of adipocyte differentiation causes type II diabetes mellitus? Nat Genet 2000; 26(1): 13PubMedCrossRefGoogle Scholar
  64. 64.
    Basu A, Jensen MD, McCann F, et al. Effects of pioglitazone versus glipizide on body fat distribution, body water content, and hemodynamics in type 2 diabetes. Diabetes Care 2006; 29(3): 510–4PubMedCrossRefGoogle Scholar
  65. 65.
    Boden G, Homko C, Mozzoli M, et al. Combined use of rosiglitazone and fenofibrate in patients with type 2 diabetes: prevention of fluid retention. Diabetes 2007; 56: 248–55PubMedCrossRefGoogle Scholar
  66. 66.
    Nesto RW, Bell D, Bonow RO, et al. Thiazolidinedione use, fluid retention, and congestive heart failure. Diabetes Care 2004; 27: 256–63PubMedCrossRefGoogle Scholar
  67. 67.
    Goudswaard AN, Furlong NJ, Rutten GE, et al. Insulin monotherapy versus combinations of insulin with oral hypoglycaemic agents in patients with type 2 diabetes mellitus. Cochrane Database Syst Rev 2004; (4): CD003418Google Scholar
  68. 68.
    Jacober SJ, Scism-Bacon JL, Zagar AJ. A comparison of intensive mixture therapy with basal insulin therapy in insulin-naive patients with type 2 diabetes receiving oral antidiabetes agents. Diabetes Obes Metab 2006 Jul; 8(4): 448–55PubMedCrossRefGoogle Scholar
  69. 69.
    Yki-Jarvinen H. Combination therapies with insulin in type 2 diabetes. Diabetes Care 2001; 24: 758–67PubMedCrossRefGoogle Scholar
  70. 70.
    Goudswaard AN, Stolk RP, Zuithoff P, et al. Starting insulin in type 2 diabetes: continue oral hypoglycemic agents? A randomized trial in primary care. J Fam Pract 2004; 53(5): 393–9PubMedGoogle Scholar
  71. 71.
    Strowig SM, Aviles-Santa ML, Raskin P. Comparison of insulin monotherapy and combination therapy with insulin and metformin or insulin and troglitazone in type 2 diabetes. Diabetes Care 2002; 25(10): 1691–8PubMedCrossRefGoogle Scholar
  72. 72.
    Janka HU, Plewe G, Riddle MC, et al. Comparison of basal insulin added to oral agents versus twice-daily premixed insulin as initial insulin therapy for type 2 diabetes. Diabetes Care 2005; 28(2): 254–9PubMedCrossRefGoogle Scholar
  73. 73.
    Makimattila S, Nikkila K, Yki-Jarvinen H. Causes of weight gain during insulin therapy with and without metformin in patients with type II diabetes mellitus. Diabetologia 1999; 42(4): 406–12PubMedCrossRefGoogle Scholar
  74. 74.
    Riddle MC, Rosenstock J, Gerich J. Insulin Glargine 4002 Study Investigators. The treat-to-target trial: randomized addition of glargine or human NPH insulin to oral therapy of type 2 diabetic patients. Diabetes Care 2003; 26(11): 3080–6PubMedCrossRefGoogle Scholar
  75. 75.
    Hermansen K, Davies M, Derezinski T, et al. A 26-week, randomized, parallel, treat-to-target trial comparing insulin 1141 detemir with NPH insulin as add-on therapy to oral glucoselowering drugs in insulin-naive people with type 2 diabetes. Diabetes Care 2006; 29(6): 1269–74PubMedCrossRefGoogle Scholar
  76. 76.
    Philis-Tsimikas A, Charpentier G, Clauson P, et al. Comparison of once-daily insulin detemir with NPH insulin added to a regimen of oral antidiabetic drugs in poorly controlled type 2 diabetes. Clin Ther 2006; 28(10): 1569–81PubMedCrossRefGoogle Scholar
  77. 77.
    Kersten S. Mechanisms of nutritional and hormonal regulation of lipogenesis. EMBO Rep 2001; 2: 282–6PubMedCrossRefGoogle Scholar
  78. 78.
    Fonseca V. Effect of thiazolidinediones on body weight in patients with diabetes mellitus. Am J Med 2003 Dec 8; 115 Suppl. 8A: 42S–8SPubMedCrossRefGoogle Scholar
  79. 79.
    Schwartz MW, Porte Jr D. Diabetes, obesity, and the brain. Science 2005; 307: 375–9PubMedCrossRefGoogle Scholar
  80. 80.
    Landstedt-Hallin L, Adamson U, Arner P, et al. Comparison of bedtime NPH or preprandial regular insulin combined with glibenclamide in secondary sulfonylurea failure [abstract]. Diabetes Care 1995; 18(8): 1183PubMedCrossRefGoogle Scholar
  81. 81.
    Lindholm A. New insulins in the treatment of diabetes mellitus. Best Pract Res Clin Gastroenterol 2002; 16(3): 475–92PubMedCrossRefGoogle Scholar
  82. 82.
    Hermansen K, Davies M. Does insulin detemir have a role in reducing risk of insulin-associated weight gain? Diabetes Obes Metab 2007; 9(3): 209–17PubMedCrossRefGoogle Scholar
  83. 83.
    Havelund S, Plum A, Ribel U, et al. The mechanism of protraction of insulin detemir, a long-acting, acylated analog of human insulin. Pharm Res 2004; 21: 1498–504PubMedCrossRefGoogle Scholar
  84. 84.
    Raslova K, Bogoev M, Raz I, et al. Insulin detemir and insulin aspart: a promising basal-bolus regimen for type 2 diabetes. Diabetes Res Clin Pract 2004; 66(2): 193–201PubMedCrossRefGoogle Scholar
  85. 85.
    Haak T, Tiengo A, Draeger E, et al. Lower within-subject variability of fasting blood glucose and reduced weight gain with insulin detemir compared to NPH insulin in patients with type 2 diabetes. Diabetes Obes Metab 2005 Jan; 7(1): 56–64PubMedCrossRefGoogle Scholar
  86. 86.
    Raslova K, Tamer SC, Clauson P, et al. Insulin detemir results in less weight gain than NPH insulin when used in basal-bolus therapy for type 2 diabetes mellitus, and this advantage increases with baseline body mass index. Clin Drug Investig 2007; 27(4): 279–85PubMedCrossRefGoogle Scholar
  87. 87.
    Rosenstock J, Davies M, Home PD, et al. Insulin detemir added to oral anti-diabetic drugs in type 2 diabetes provides glycemic control comparable to insulin glargine with less weight gain [abstract no. 555-P]. Diabetes 2006; 55 Suppl. 1: A132Google Scholar
  88. 88.
    Heise T, Nosek L, Ronn BB, et al. Lower within-subject variability of insulin detemir in comparison to NPH insulin and insulin glargine in people with type 1 diabetes. Diabetes 2004; 53: 1614–20PubMedCrossRefGoogle Scholar
  89. 89.
    Hordern SV, Wright JE, Umpleby AM, et al. Comparison of the effects on glucose and lipid metabolism of equipotent doses of insulin detemir and NPH insulin with a 16-h euglycaemic clamp. Diabetologia 2005; 48: 420–6PubMedCrossRefGoogle Scholar
  90. 90.
    Plank J, Bodenlenz M, Sinner F, et al. A double-blind, randomized, dose-response study investigating the pharmacodynamic and pharmacokinetic properties of the long-acting insulin analog detemir. Diabetes Care 2005; 28: 1107–12PubMedCrossRefGoogle Scholar
  91. 91.
    Hennige AM, Sartorius T, Tschritter O, et al. Tissue selectivity of insulin detemir action in vivo. Diabetologia 2006; 49(6): 1274–82PubMedCrossRefGoogle Scholar
  92. 92.
    Drucker DJ, Nauck MA. The incretin system: glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors in type 2 diabetes. Lancet 2006; 368: 1696–705PubMedCrossRefGoogle Scholar
  93. 93.
    Perfetti R, Merkel P. Glucagon-like peptide-1: a major regulator of pancreatic beta-cell function. Eur J Endocrinol 2000; 143(6): 717–25PubMedCrossRefGoogle Scholar
  94. 94.
    Vilsbøll T, Krarup T, Deacon CF, et al. Reduced postprandial concentrations of intact biologically active glucagon-like peptide 1 in type 2 diabetic patients. Diabetes 2001; 50(3): 609–13PubMedCrossRefGoogle Scholar
  95. 95.
    Vilsbøll T, Krarup T, Madsbad S, et al. No reactive hypoglycaemia in type 2 diabetic patients after subcutaneous administration of GLP-1 and intravenous glucose. Diabet Med 2001; 18(2): 144–9PubMedCrossRefGoogle Scholar
  96. 96.
    Meier JJ, Gallwitz B, Salmen S, et al. Normalization of glucose concentrations and deceleration of gastric emptying after solid meals during intravenous glucagon-like peptide 1 in patients with type 2 diabetes. J Clin Endocrinol Metab 2003; 88(6): 2719–25PubMedCrossRefGoogle Scholar
  97. 97.
    Zander M, Madsbad S, Madsen JL, et al. Effect of 6-week course of glucagon-like peptide 1 on glycaemic control, insulin sensitivity, and beta-cell function in type 2 diabetes: a parallel-group study. Lancet 2002 Mar 9; 359(9309): 824–30PubMedCrossRefGoogle Scholar
  98. 98.
    Bulotta A, Hui H, Anastasi E, et al. Cultured pancreatic ductal cells undergo cell cycle re-distribution and beta-cell-like differentiation in response to glucagon-like peptide-1. J Mol Endocrinol 2002; 29(3): 347–60PubMedCrossRefGoogle Scholar
  99. 99.
    Farilla L, Bulotta A, Hirshberg B, et al. Glucagon-like peptide 1 inhibits cell apoptosis and improves glucose responsiveness of freshly isolated human islets. Endocrinology 2003 Dec; 144(12): 5149–58PubMedCrossRefGoogle Scholar
  100. 100.
    Kendall DM, Riddle MC, Rosenstock J, et al. Effects of exenatide (exendin-4) on glycemic control over 30 weeks in patients with type 2 diabetes treated with metformin and a sulfonylurea. Diabetes Care 2005; 28(5): 1083–91PubMedCrossRefGoogle Scholar
  101. 101.
    Buse JB, Henry RR, Han J, et al. Exenatide-113 Clinical Study Group. Effects of exenatide (exendin-4) on glycemic control over 30 weeks in sulfonylurea-treated patients with type 2 diabetes. Diabetes Care 2004; 27(11): 2628–35PubMedCrossRefGoogle Scholar
  102. 102.
    DeFronzo RA, Ratner RE, Han J, et al. Effects of exenatide (exendin-4) on glycemic control and weight over 30 weeks in metformin-treated patients with type 2 diabetes. Diabetes Care 2005; 28(5): 1092–100PubMedCrossRefGoogle Scholar
  103. 103.
    Heine RJ, Van Gaal LF, Johns D, et al. Exenatide versus insulin glargine in patients with suboptimally controlled type 2 diabetes. Ann Intern Med 2005; 143: 559–69PubMedGoogle Scholar
  104. 104.
    Edwards CM, Stanley SA, Davis R, et al. Exendin-4 reduces fasting and postprandial glucose and decreases energy intake in healthy volunteers. Am J Physiol Endocrinol Metab 2001; 281(1): E155–61PubMedGoogle Scholar
  105. 105.
    Szayna M, Doyle ME, Betkey JA, et al. Exendin-4 decelerates food intake, weight gain, and fat deposition in Zucker rats. Endocrinology 2000; 141(6): 1936–41PubMedCrossRefGoogle Scholar
  106. 106.
    Knudsen LB, Nielsen PF, Huusfeldt PO, et al. Potent derivatives of glucagon-like peptide-1 with pharmacokinetic properties suitable for once daily administration. J Med Chem 2000 May 4; 43(9): 1664–9PubMedCrossRefGoogle Scholar
  107. 107.
    Vilsbøll T, Zdravkovic M, Le-Thi T, et al. Liraglutide significantly improves glycemic control, and lowers body weight without risk of either major or minor hypoglycemic episodes in subjects with type 2 diabetes [abstract]. Diabetes 2006; 55 Suppl. 1: A27CrossRefGoogle Scholar
  108. 108.
    Madsbad S, Schmitz O, Ranstam J, et al. NN2211-1310 International Study Group. Improved glycemic control with no weight increase in patients with type 2 diabetes after once-daily treatment with the long-acting glucagon-like peptide 1 analog liraglutide (NN2211): a 12-week, double-blind, randomized, controlled trial. Diabetes Care 2004; 27(6): 1335–42PubMedCrossRefGoogle Scholar
  109. 109.
    Ahren B, Gomis R, Standl E, et al. Twelve- and 52 week efficacy of the dipeptidyl peptidase IV inhibitor LAF237 in metformin-treated patients with type 2 diabetes. Diabetes Care 2004; 27(12): 2874–80PubMedCrossRefGoogle Scholar
  110. 110.
    Ristic S, Byiers S, Foley J, et al. Improved glycaemic control with dipeptidyl peptidase-4 inhibition in patients with type 2 diabetes: vildagliptin (LAF237) dose response. Diabetes Obes Metab 2005; 7(6): 692–8PubMedCrossRefGoogle Scholar
  111. 111.
    Raz I, Hanefeld M, Xu L, et al. Efficacy and safety of the dipeptyl peptidase-4 inhibitor as monotherapy in patients with type 2 diabetes. Diabetologia 2006; 49: 2564–71 1142PubMedCrossRefGoogle Scholar
  112. 112.
    Hollander PA, Levy P, Fineman MS, et al. Pramlintide as an adjunct to insulin therapy improves long-term glycemic and weight control in patients with type 2 diabetes: a 1-year randomized controlled trial. Diabetes Care 2003; 26(3): 784–90PubMedCrossRefGoogle Scholar
  113. 113.
    Ratner RE, Want LL, Fineman MS, et al. Adjunctive therapy with the amylin analogue pramlintide leads to a combined improvement in glycemic and weight control in insulin-treated subjects with type 2 diabetes. Diabetes Technol Ther 2002; 4(1): 51–61PubMedCrossRefGoogle Scholar
  114. 114.
    Mari A, Sallas WM, He YL, et al. Vildagliptin, a dipeptidyl peptidase-IV inhibitor, improves model-assessed beta-cell function in patients with type 2 diabetes. J Clin Endocrinol Metab 2005; 90(8): 4888–94PubMedCrossRefGoogle Scholar
  115. 115.
    Herman G, Hanefeld M, Wu M, et al. Effect of MK-0431, a dipeptidyl peptidase IV (DPP IV) inhibitor, on glycemic control after 12 weeks in patients with type 2 diabetes [abstract]. Diabetes 2005; 54 Suppl. 1: 541PGoogle Scholar
  116. 116.
    Young AA. Amylin’s physiology and its role in diabetes. Curr Opin Endocrinol Diabetes 1997; 4: 282–90CrossRefGoogle Scholar
  117. 117.
    Weyer C, Maggs DG, Young AA, et al. Amylin replacement with pramlintide as an adjunct to insulin therapy in type 1 and type 2 diabetes mellitus: a physiological approach toward improved metabolic control. Curr Pharm Des 2001; 7(14): 1353–73PubMedCrossRefGoogle Scholar
  118. 118.
    Fineman M, Weyer C, Maggs DG, et al. The human amylin analog, pramlintide, reduces postprandial hyperglucagonemia in patients with type 2 diabetes mellitus. Horm Metab Res 2002; 34(9): 504–8PubMedCrossRefGoogle Scholar
  119. 119.
    Nyholm B, Orskov L, Hove KY, et al. The amylin analog pramlintide improves glycemic control and reduces postprandial glucagon concentrations in patients with type 1 diabetes mellitus. Metabolism 1999; 48(7): 935–41PubMedCrossRefGoogle Scholar
  120. 120.
    Hollander P, Maggs DG, Ruggles JA, et al. Effect of pramlintide on weight in overweight and obese insulin-treated type 2 diabetes patients. Obes Res 2004; 12(4): 661–8PubMedCrossRefGoogle Scholar
  121. 121.
    Rushing PA, Hagan MM, Seeley RJ, et al. Inhibition of central amylin signaling increases food intake and body adiposity in rats [abstract]. Endocrinology 2001; 142(11): 5035PubMedCrossRefGoogle Scholar
  122. 122.
    Maggs DG, Fineman M, Kornstein J, et al. Pramlintide reduces postprandial glucose excursions when added to insulin lispro in subjects with type 2 diabetes: a dose-timing study. Diabetes Metab Res Rev 2004; 20(1): 55–60PubMedCrossRefGoogle Scholar

Copyright information

© Adis Data Information BV 2007

Authors and Affiliations

  1. 1.Aarhus University HospitalAarhusDenmark

Personalised recommendations