Current Diabetes Reports

, Volume 7, Issue 5, pp 369–375

Exenatide and rimonabant: New treatments that may be useful in the management of diabetes and obesity



Diabetes mellitus and obesity have become increasingly prevalent problems worldwide. Unfortunately, with traditionally prescribed glucose-lowering medications most individuals with diagnosed diabetes do not achieve and maintain adequate glycemic control over time; it may be even more challenging to lower blood glucose to an appropriate level without inducing a significant associated weight gain. Exenatide and rimonabant are recently developed agents that have demonstrated benefit in both glucose lowering and reduction of body weight. These medications may well prove to be attractive alternatives or additions to our more established diabetes therapies; however, these drugs have a side-effect profile that may limit their applicability to certain populations.


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References and Recommended Reading

  1. 1.
    Turner R: Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). UK Prospective Diabetes Study Group. Lancet 1998, 352:837–853.CrossRefGoogle Scholar
  2. 2.
    Saydah SH, Fradkin J, Cowie CC: Poor control of risk factors for vascular disease among adults with previously diagnosed diabetes. JAMA 2004, 291:335–342.PubMedCrossRefGoogle Scholar
  3. 3.
    Curioni CC, Lourenco PM: Long-term weight loss after diet and exercise—a systematic review. Int J Obes 2005, 29:1168–1174.CrossRefGoogle Scholar
  4. 4.
    Nauck MA, Homberger F, Siegel EG, et al.: Incretin effects of increasing glucose loads in man calculated from venous insulin and C-peptide responses. J Clin Endocrinol Metab 1986, 63:492–498.PubMedCrossRefGoogle Scholar
  5. 5.
    Mikhail N: Exenatide: a novel approach for treatment of type 2 diabetes. South Med J 2006, 99:1271–1280.PubMedGoogle Scholar
  6. 6.
    Lebovitz H: Diabetes: assessing the pipeline. Atheroscler Suppl 2005, 7:43–49.CrossRefGoogle Scholar
  7. 7.
    Holst JJ: Glucagon-like peptide-1: from extract to agent. Diabetologia 2005, 49:253–260.CrossRefGoogle Scholar
  8. 8.
    Nauck MA, Meier JJ: Glucagon-like peptide 1 and its derivatives in the treatment of diabetes. Regul Pept 2005, 128:135–148.PubMedCrossRefGoogle Scholar
  9. 9.
    Drucker DJ, Nauck MA: The incretin system: glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors in type 2 diabetes. Lancet 2006, 368:1696–1705.PubMedCrossRefGoogle Scholar
  10. 10.
    Zander M, Madsbad S, Madsen JL, et al.: Effect of 6-week course of glucagons-like peptide 1 on glycaemic control, insulin sensitivity, and beta-cell function in type 2 diabetes: a parallel-group study. Lancet 2002, 359:824–830.PubMedCrossRefGoogle Scholar
  11. 11.
    Dunning BE, Foley JE, Ahren B: Alpha cell function in health and disease: influence of glucagons-like peptide-1. Diabetologia 2005, 48:1700–1713.PubMedCrossRefGoogle Scholar
  12. 12.
    Kendall DM, Kim D, Maggs D: Incretin mimetics and dipeptidyl peptidase-IV inhibitors: a review of emerging therapies for type 2 diabetes. Diabetes Technol Ther 2006, 8:385–396.PubMedCrossRefGoogle Scholar
  13. 13.
    Hinnen D, Nielsen LL, Waninger A, et al.: Incretin mimetics and DPP-IV inhibitors: new paradigms for the treatment of type 2 diabetes. J Am Board Fam Med 2006, 19:612–620.PubMedCrossRefGoogle Scholar
  14. 14.
    Keating GM: Exenatide. Drugs 2005, 65:1681–1692.PubMedCrossRefGoogle Scholar
  15. 15.
    Schnabel CA, Wintle M, Kolterman O: Metabolic effects of the incretin mimetic exenatide in the treatment of type 2 diabetes. Vasc Health Risk Manag 2006, 2:69–77.PubMedCrossRefGoogle Scholar
  16. 16.
    Fehse F, Trautmann M, Holst JJ, et al.: Exenatide augments first-and second-phase insulin secretion in response to intravenous glucose in subjects with type 2 diabetes. J Clin Endocrinol Metab 2005, 90:5991–5997.PubMedCrossRefGoogle Scholar
  17. 17.
    Buse JB, Fineman MS, Henry RR: Effects of exenatide (exendin-4) on glycemic control over 30 weeks in sulfonylurea-treated patients with type 2 diabetes. Diabetes Care 2004, 27:2628–2635.PubMedCrossRefGoogle Scholar
  18. 18.
    DeFronzo RA, Kim DD, Ratner RE: Effects of exenatide (exendin-4) on glycemic control and weight over 30 weeks in metformin-treated patients with type 2 diabetes. Diabetes Care 2005, 28:1092–1100.PubMedCrossRefGoogle Scholar
  19. 19.
    Kendall DM, Kim DD, Riddle MC: 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, 28:1083–1091.PubMedCrossRefGoogle Scholar
  20. 20.
    Blonde L, Klein EJ, Han J, et al.: Interim analysis of the effects of exenatide treatment on A1C, weight and cardiovascular risk factors over 82 weeks in 314 overweight patients with type 2 diabetes. Diabetes Obes Metab 2006, 8:436–447.PubMedCrossRefGoogle Scholar
  21. 21.
    Ratner RE, Maggs D, Nielsen LL, et al.: Long-term effects of exenatide therapy over 82 weeks on glycaemic control and weight in over-weight metformin-treated patients with type 2 diabetes mellitus. Diabetes Obes Metab 2006, 8:419–428.PubMedCrossRefGoogle Scholar
  22. 22.
    Riddle MC, Henry RR, Poon TH, et al.: Exenatide elicits sustained glycaemic control and progressive reduction of body weight in patients with type 2 diabetes inadequately controlled by sulphonylureas with or without metformin. Diabetes Metab Res Rev 2006, 22:483–491.PubMedCrossRefGoogle Scholar
  23. 23.
    Buse JB, Klonoff DC, Nielsen LL, et al.: Metabolic effects of two years of exenatide treatment on diabetes, obesity, and hepatic biomarkers in patients with type 2 diabetes: an interim analysis of data from the open-label, uncontrolled extension of three double-blind, placebo-controlled trials. Clin Ther 2007, 29:139–153.PubMedCrossRefGoogle Scholar
  24. 24.
    Zinman B, Hoogwerf BJ, Duran Garcia S, et al.: The effect of adding exenatide to a thiazolidinedione in suboptimally controlled type 2 diabetes. Ann Intern Med 2007, 146:477–485.PubMedGoogle Scholar
  25. 25.
    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, 143:559–569.PubMedGoogle Scholar
  26. 26.
    Nauck MA, Duran S, Kim D, et al.: A comparison of twice-daily exenatide and biphasic insulin aspart in patients with type 2 diabetes who were suboptimally controlled with a sulfonylurea and metformin: a non-inferiority study. Diabetologia 2007, 50:259–267.PubMedCrossRefGoogle Scholar
  27. 27.
    Yoo BK: Exenatide: a new option for the treatment of type 2 diabetes. Ann Pharmacother 2006, 40:1777–1784.PubMedCrossRefGoogle Scholar
  28. 28.
    Amylin Pharmaceuticals: Exenatide prescribing information. Accessed May 14, 2007.
  29. 29.
    Tushuizen ME, Bunck ME, Pouwels MC, et al.: Incretin mimetics as a novel therapeutic option for hepatic steatosis. Liver Int 2006, 26:1015–1017.PubMedCrossRefGoogle Scholar
  30. 30.
    Kim D, MacConnell L, Zhuang D, et al.: Safety and efficacy of a once-weekly, long-acting release formulation of exenatide over 15 weeks in patients with type 2 diabetes (abstract 487-P). Diabetes 2006, 55:116.Google Scholar
  31. 31.
    Despres JP, Lemieux I, Almeras N: Contribution of CB1 blockade to the management of high-risk abdominal obesity. Int J Obes 2006, 30:S44–S52.CrossRefGoogle Scholar
  32. 32.
    Carai MAM, Colombo G, Maccioni P, et al.: Efficacy of rimonabant and other cannabinoid CB1 receptor antagonists in reducing food intake and body weight: preclinical and clinical data. CNS Drug Rev 2006, 12:91–99.PubMedCrossRefGoogle Scholar
  33. 33.
    Woods SC: The endocannabinoid system: mechanisms behind metabolic homeostasis and imbalance. Am J Med 2007, 120:S9–S17.PubMedCrossRefGoogle Scholar
  34. 34.
    Kyrou I, Valsamakis G, Tsigos C: The endocannabinoid system as a target for the treatment of visceral obesity and metabolic syndrome. Ann N Y Acad Sci 2006, 1083:270–305.PubMedCrossRefGoogle Scholar
  35. 35.
    Woods SC: Role of the endocannabinoid system in regulating cardiovascular and metabolic risk factors. Am J Med 2007, 120:S19–S25.PubMedCrossRefGoogle Scholar
  36. 36.
    Engeli S, Bohnke J, Feldpausch M, et al.: Activation of the peripheral endocannabinoid system in human obesity. Diabetes 2005, 54:2838–2843.PubMedCrossRefGoogle Scholar
  37. 37.
    Van Gaal LF, Rissanan AM, Scheen AJ, et al.: Effects of the cannabinoid-1 receptor blocker rimonabant on weight reduction and cardiovascular risk factors in overweight patients: 1-year experience from the RIO-Europe study. Lancet 2005, 365:1389–1397.PubMedCrossRefGoogle Scholar
  38. 38.
    Despres JP, Golay A, Sjostrom L, et al.: Effects of rimonabant on metabolic risk factors in overweight patients with dyslipidemia. N Engl J Med 2005, 353:2121–2134.PubMedCrossRefGoogle Scholar
  39. 39.
    Pi-Sunyer FX, Aronne LJ, Heshmati HM, et al.: Effect of rimonabant, a cannabinoid-1 receptor blocker, on weight and cardiometabolic risk factors in overweight or obese patients. JAMA 2006, 295:761–775.PubMedCrossRefGoogle Scholar
  40. 40.
    Scheen AJ, Finer N, Hollander P, et al.: Efficacy and tolerability of rimonabant in overweight or obese patients with type 2 diabetes: a randomized controlled study. Lancet 2006, 368:1660–1672.PubMedCrossRefGoogle Scholar
  41. 41.
    Curioni C, Andre C: Rimonabant for overweight or obesity. Cochrane Database Syst Rev 2006, (4):CD006162.Google Scholar
  42. 42.
    Boyd ST, Fremming BA: Rimonabant—a selective CB1 antagonist. Ann Pharmacother 2005, 39:684–690.PubMedCrossRefGoogle Scholar
  43. 43.
    Padwal RS, Majumdar SR: Drug treatments for obesity: orlistat, sibutramine, and rimonabant. Lancet 2007, 369:71–77.PubMedCrossRefGoogle Scholar
  44. 44.
    Patel PN, Pathak R: Rimonabant: a novel selective cannabinoid-1 receptor antagonist for the treatment of obesity. Am J Health Syst Pharm 2007, 64:481–489.PubMedCrossRefGoogle Scholar
  45. 45.
    Gadde KM, Allison DB: Cannabinoid-1 receptor antagonist, rimonabant, for management of obesity and related risks. Circulation 2006, 114:974–984.PubMedCrossRefGoogle Scholar
  46. 46.
    Le Foll B, Goldberg SR: Cannabinoid CB1 receptor antagonists as promising new medications for drug dependence. J Pharmacol Exp Ther 2005, 312:875–883.PubMedCrossRefGoogle Scholar

Copyright information

© Current Medicine Group LLC 2007

Authors and Affiliations

  1. 1.Division of Endocrinology, Metabolism, and NutritionDuke University Medical CenterDurhamUSA

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