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Dipeptidyl Peptidase-4 Inhibitors in the Elderly: More Benefits or Risks?

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Abstract

Several studies have shown a high prevalence of type 2 diabetes mellitus (T2DM) in the elderly, characterized by a paucity of symptoms, which represents an obstacle for an early diagnosis. Frequently, T2DM in the elderly is diagnosed when a complication occurs, among which are cognitive disorders and/or affective disturbances. Moreover, hypoglycemia is a frequent side effect of therapeutic treatment with insulin, sulfonylureas or glinides, while other treatments (metformin, acarbose, thiazolidinediones, glucagon-like peptide-1 [GLP-1] receptor agonists, and dipeptidyl peptidase-4 [DPP4] inhibitors) are capable of reducing hyperglycemia without inducing hypoglycemia. Thus, considering that older persons are a very heterogeneous group of individuals, management of T2DM in the elderly is challenging but there are no available specific treatment goals or treatment algorithms for older diabetic patients. Metformin is the recommended first-line therapy in all T2DM patients. When metformin is not sufficient to achieve the desired therapeutic targets, a second drug can be added. Available options include sulfonylureas, meglitinides, alfa-glucosidase inhibitors, pioglitazone, insulin, GLP-1 receptor agonists, and DPP-4 inhibitors. The most intriguing therapy for older patients is the one based on the so-called incretins, i.e., gastrointestinal hormones that, mainly secreted in the postprandial phase, stimulate insulin secretion and inhibit glucagon secretion. The two most important human incretins are GLP-1 and glucose-dependent insulinotropic peptide (GIP). These hormones potentiate the acute effects of glucose on pancreatic alfa and beta cells, thus stimulating insulin secretion, and only GLP-1 inhibits glucagon secretion in a glucose-dependent manner (that is, only when glucose levels are increased); as a result, they reduce hyperglycemia with virtually no hypoglycemic risk. Due to their characteristics, DPP-4 inhibitors seem to be particularly interesting as potential agents for the treatment of older patients with T2DM.

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References

  1. Sloan FA, Bethel MA, Ruiz D Jr, Shea AM, Feinglos MN. The growing burden of diabetes mellitus in the US elderly population. Arch Intern Med. 2008;168:192–199.

    Article  PubMed  Google Scholar 

  2. Pratley RE, Rosenstock J, Sunyer FXP, et al. Management of type 2 diabetes in treatment-naive eldery patients. Diabetes Care. 2007;30:3017–3022.

    Article  PubMed  CAS  Google Scholar 

  3. Fagot-Campagna A, Bourdel-Marchasson I, Simon D. Burden of diabetes in an aging population: prevalence, incidence, mortality, characteristics and quality of care. Diabetes Care. 2005;31:5S35–5S52.

    Google Scholar 

  4. Keymel S, Heinen Y, Balzer J, et al. Characterization of macro and microvascular function and structure in patients with type 2 diabetes mellitus. Am J Cardiovasc Dis. 2011;1:68–75.

    PubMed  CAS  Google Scholar 

  5. Sinclair AJ, Robert IE, Croxson SC. Mortality in older people with diabetes mellitus. Diabet Med. 1997;14:639–647.

    Article  PubMed  CAS  Google Scholar 

  6. Fontbonne A, Berr C, Ducimetière P, Alpérovitch A. Changes in cognitive abilities over a 4-year period are unfavorably affected in elderly diabetic subjects: results of the Epidemiology of Vascular Aging Study. Diabetes Care. 2001;24:366–370.

    Article  PubMed  CAS  Google Scholar 

  7. Rizzo MR, Marfella R, Barbieri M, et al. Relationships between daily acute glucose fluctuations and cognitive performance among aged type 2 diabetic patients. Diabetes Care. 2010;33:2169–2174.

    Article  PubMed  Google Scholar 

  8. Munshi M, Grande L, Hayes M, et al. Cognitive dysfunction is associated with poor diabetes control in older adults. Diabetes Care. 2006;29:1794–1799.

    Article  PubMed  Google Scholar 

  9. Bourdel-Marchasson I, Berrut G. Caring the elderly diabetic patient with respect to concepts of successful aging and frailty. Diabetes Metab. 2005;31:5S13–5S19.

    Article  PubMed  Google Scholar 

  10. Doucet J. Use of antidiabetic drugs in elderly patients. Diabetes Metab. 2005;31:5S98–5S104.

    Article  PubMed  CAS  Google Scholar 

  11. Bourdel-Marchasson I, Doucet J, Bauduceau B, et al. Key priorities in managing glucose control in older people with diabetes. J Nutr Health Aging. 2009;13:685–691.

    Article  PubMed  CAS  Google Scholar 

  12. Volpato S, Maraldi C, Fellin R. Type 2 diabetes and risk for functional decline and disability in older persons. Curr Diabetes Rev. 2010;6:134–143.

    Article  PubMed  Google Scholar 

  13. Solanki RK, Dubey V, Munshi D. Neurocognitive impairment and comorbid depression in patients of diabetes mellitus. Int J Diabetes Dev Ctries. 2009;29:133–138.

    Article  PubMed  CAS  Google Scholar 

  14. Neumiller JJ, Setter SM. Pharmacologic management of the older patient with type 2 diabetes mellitus. Am J Geriatr Pharmacother. 2009;7:324–342.

    Article  PubMed  CAS  Google Scholar 

  15. Sloan FA, Betel MA, Ruiz D, et al. The growing burden of diabetes mellitus in the US eldery population. Arch Intern Med. 2008;168:192–199.

    Article  PubMed  Google Scholar 

  16. Schienkiewitz A, Schulze MB, Hoffmann K, Kroke A, Boeing H. Body mass index history and risk of type 2 diabetes: results from the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam Study. Am J Clin Nutr. 2006;84:427–433.

    PubMed  CAS  Google Scholar 

  17. Meneilly GS, Terrier D. Diabetes in elderly adults. J Gerontol A Biol Med Sci. 2001;56:M5–M13.

    Article  CAS  Google Scholar 

  18. Meneilly GS. Diabetes. In: Evans JG, Williams TF, Beattie BL et al. Oxford Textbook of Geriatric Medicine. 2nd edition. New York: Oxford University Press; 2000:210–217.

    Google Scholar 

  19. Abbatecola AM, Maggi S, Paolisso G. New approaches to treating type 2 diabetes mellitus in the eldery. Role of incretin therapies. Drugs Aging. 2008;25:913–925.

    Article  PubMed  CAS  Google Scholar 

  20. Kempen JH, O’Colmain BJ, Leske MC, et al. The prevalence of diabetic retinopathy among adults in the United States. Arch Ophthalmol. 2004;122:522–563.

    Google Scholar 

  21. Feil D, Weinreb J, Sultzer D. Psychiatric disorders and psychotropic medication use in elderly persons with diabetes. Ann Long Term Care. 2006;59:148–153.

    Google Scholar 

  22. Amiel SA, Dixon T, Mann R, et al. Hypoglycaemia in type 2 diabetes. Diabet Med. 2008;25:245–254.

    Article  PubMed  CAS  Google Scholar 

  23. Chelliah A, Burge MR. Hypoglycaemia in elderly patients with diabetes mellitus: causes and strategies for prevention. Drugs Aging. 2004;21:511–530.

    Article  PubMed  CAS  Google Scholar 

  24. Bourdel-Marchasson I, Schweizer A, Dejager S. Incretin therapies in the management of elderly patients with type 2 diabetes mellitus. Hosp Pract (Minneap). 2011;39:7–21.

    Article  Google Scholar 

  25. Landi F, Abbatecola AM, Provinciali M, et al. Moving against frailty: does physical activity matter? Biogerontology. 2010;11:537–545.

    Article  PubMed  Google Scholar 

  26. Miller ME, Bonds DE, Gerstein HC, et al. ACCORD Investigators. The effects of baseline characteristics, glycaemia treatment approach, and glycated haemoglobin concentration on the risk of severe hypoglycaemia: post hoc epidemiological analysis of the ACCORD study. BMJ. 2010;340:b5444.

    Article  PubMed  Google Scholar 

  27. Whitmer RA, Karter AJ, Jaffe K, et al. Hypoglycaemic episodes and risk of dementia in older patients with type 2 diabetes mellitus. JAMA 2009;301:1565–1572.

    Article  PubMed  CAS  Google Scholar 

  28. Monami M, Cresci B, Colombini A, et al. Bone fractures and hypoglycemic treatment in type 2 diabetic patients: a case-control study. Diabetes Care. 2008;31:199–203.

    Article  PubMed  Google Scholar 

  29. Mannucci E, Monami M, Lamanna C, Gori F, Marchionni N. Prevention of cardiovascular disease through glycemic control in type 2 diabetes: a meta-analysis of randomized clinical trials. Nutr Metab Cardiovasc Dis. 2009;19:604–612.

    Article  PubMed  CAS  Google Scholar 

  30. Skyler JS, Bergenstal R, Bonow RO, et al. Intensive Glycemic Control and the Prevention of Cardiovascular Events: Implications of the ACCORD, ADVANCE, and VA Diabetes Trials. A position statement of the American Diabetes Association and a scientific statement of the American College of Cardiology Foundation and the American Heart Association. Circulation 2009;119:351–357.

    Article  PubMed  Google Scholar 

  31. Bonds DE, Miller ME, Bergenstal R. The associations between symptomatic, severe hypoglycaemia and morality in type 2 diabetes: retrospective epidemiological analysis of the ACCORD study. BMJ 2010; 340:b4909.

    Article  PubMed  Google Scholar 

  32. Barnett AH. Avoiding hypoglycaemia while achieving good glycaemic control in type 2 diabetes though optimal use of oral agent therapy. Curr Med Res Opin. 2010;26:1333–1342.

    Article  PubMed  CAS  Google Scholar 

  33. American Diabetes Association. Standards of medical care in Diabetes — 2010. Diabetes Care. 2010;33:S11–S61.

    Article  Google Scholar 

  34. Schernthaner G, Barnett AH, Betteridge DJ, et al. Is the ADA/EASD algorithm for the management of type 2 diabetes (January 2009) based on evidence or opinion? A critical analysis. Diabetologia. 2010; 53:1258–1269.

    Article  PubMed  CAS  Google Scholar 

  35. Nathan DM. Initial management of glycemia in type 2 diabetes mellitus. N Engl J Med. 2002;347:1342–1348.

    Article  PubMed  Google Scholar 

  36. Gross JL, Kramer CK, Leitão CB, et al. Diabetes and Endocrinology Meta-analysis Group (DEMA). Effect of antihyperglycemic agents added to metformin and a sulfonylurea on glycemic control and weight gain in type 2 diabetes: a network meta-analysis. Ann Intern Med. 2011;154:672–679.

    PubMed  Google Scholar 

  37. Scognamiglio R, Avogaro A, Vigili de Kreutzenberg S, et al. Effects of treatment with sulfonylurea drugs or insulin on ischemia-induced myocardial dysfunction in type 2 diabetes. Diabetes. 2002;51:808–812.

    Article  PubMed  CAS  Google Scholar 

  38. Horsdal HT, Søndergaard F, Johnsen SP, Rungby J. Antidiabetic treatments and risk of hospitalization with myocardial infarction: a nationwide casecontrol study. Pharmacoepidemiol Drug Saf. 2011;20:331–337.

    Article  PubMed  CAS  Google Scholar 

  39. Bennett WL, Maruthur NM, Singh S, et al. Comparative effectiveness and safety of medications for type 2 diabetes: an update including new drugs and 2-drug combinations. Ann Intern Med. 2011;154:602–613.

    PubMed  Google Scholar 

  40. Schwartz AV, Hillier TA, Sellmeyer DE, et al. Older women with diabetes have a higher risk of falls. A prospective study. Diabetes Care. 2002;25:1749–1754.

    Article  PubMed  Google Scholar 

  41. Monami M, Marchionni N, Mannucci E. Glucagon-like peptide-1 receptor agonists in type 2 diabetes: a meta-analysis of randomized clinical trials. Eur J Endocrinol. 2009;160:909–917.

    Article  PubMed  CAS  Google Scholar 

  42. 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.

    Article  PubMed  CAS  Google Scholar 

  43. Fielding RA, Vellas B, Evans WJ, et al. Sarcopenia: an undiagnosed condition in older adults. Current consensus definition: prevalence, etiology, and consequences. International working group on sarcopenia. J Am Med Dir Assoc. 2011;12:249–256.

    Article  PubMed  Google Scholar 

  44. Monami M, Iacomelli I, Marchionni N, Mannucci E. Dipeptydil peptidase-4 inhibitors in type 2 diabetes: a meta-analysis of randomized clinical trials. Nutr Metab Cardiovasc Dis. 2010;20:224–235.

    Article  PubMed  CAS  Google Scholar 

  45. Willemen MJ, Mantel-Teeuwisse AK, Straus SM, Meyboom RH, Egberts TC, Leufkens HG. Use of dipeptidyl peptidase-4 inhibitors and the reporting of infections: a disproportionality analysis in the World Health Organization VigiBase. Diabetes Care. 2011;34:369–374.

    Article  PubMed  Google Scholar 

  46. Monami M, Dicembrini I, Martelli D, Mannucci E. Safety of dipeptidyl-peptidase 4 inhbitors. A meta-analysis of randomized clinical trials. Curr Med Res Opin. 2011;27(Suppl 3):57–64.

    Article  PubMed  CAS  Google Scholar 

  47. Monami M, Dicembrini I, Antenore A, Mannucci E. Dipeptidyl peptidase 4 inhibitors and bone fractures. A meta-analysis of randomized clinical trials. Diabetes Care. 2011;34:2474–2476.

    Article  PubMed  Google Scholar 

  48. Monami M, Cremasco F, Lamanna C, et al. Predictors of response to dipeptidyl peptidase-4 inhibitors: evidence from randomized clinical trials. Diabetes Metab Res Rev. 2011;27:362–372.

    Article  PubMed  CAS  Google Scholar 

  49. 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;27:2874–2880.

    Article  PubMed  CAS  Google Scholar 

  50. Rosenstock J, Baron MA, Dejager S, et al. Comparison of vildagliptin and rosiglitazone monotherapy in patients with type 2 diabetes: a 24-week, double-blind, randomized trial. Diabetes Care. 2007;30:217–223.

    Article  PubMed  CAS  Google Scholar 

  51. Fonseca V, Schweizer A, Albrecht D, et al. Addition of vildagliptin to insulin improves glycaemic control in type 2 diabetes. Diabetologia. 2007;50:1148–1155.

    Article  PubMed  CAS  Google Scholar 

  52. Blonde L, Dagogo-Jack S, Banerji MA, et al. Comparison of vildagliptin and thiazolidinedione as add-on therapy in patients inadequately controlled with metformin: results of the GALIANT trial—a primary care, type 2 diabetes study. Diabetes Obes Metab. 2009;11:978–986.

    Article  PubMed  CAS  Google Scholar 

  53. Schweizer A, Dejager S, Bosi E. Comparison of vildagliptin and metformin monotherapy in elderly patients with type 2 diabetes: a 24-week, double-blind, randomized trial. Diabetes Obes Metab. 2009;11:804–812.

    Article  PubMed  CAS  Google Scholar 

  54. Schweizer A, Dejager S, Foley J.E, Shao Q, Kothny W. Clinical experience with vildagliptinin the management of type 2 diabetes in a patient population ≥75 years: a pooled analysis from a database of clinical trials. Diabetes Obes Metab 2011:13:55–64.

    Article  PubMed  CAS  Google Scholar 

  55. Ligueros-Saylan M, Foley JE, Schweizer A, Couturier A, Kothny W. An assessment of adverse effects of vildagliptin versus comparators on the liver, the pancreas, the immune system, the skin and in patients with impaired renal function from a large pooled database of phase II and III clinical trials. Diabetes Obes Metab. 2010;12:495–509.

    Article  PubMed  CAS  Google Scholar 

  56. Lukashevich V, Schweizer A, Shao Q, Groop P-H, Kothny W. Safety and efficacy of vildagliptin versus placebo in patients with type 2 diabetes and moderate or severe renal imapirment: a prospective 24-week randomized placebo-controlled trial. Diabetes Obes Metab. 2011:13:947–954.

    Article  PubMed  CAS  Google Scholar 

  57. Scheen A. J. Pharmacokinetic of dipeptidyl peptidase-4 inhibitors. Diabetes Obes Metab 2010:12:648–658.

    Article  PubMed  CAS  Google Scholar 

  58. Marfella R, Barbieri M, Grella R, Rizzo MR, Nicoletti GF, Paolisso G. Effects of vildagliptin twice daily vs. sitagliptin once daily on 24-hour acute glucose fluctuations. J Diabetes Complications. 2010;24:79–83.

    Article  PubMed  Google Scholar 

  59. Barzilai N, Guo H, Mahoney EM et al. Efficacy and tolerability of sitagliptin monotherapy in elderly patients with type 2 diabetes: a randomized, double-blind, placebo-controlled trial. Curr Med Res Opin. 2011;27:1049–1058.

    Article  PubMed  CAS  Google Scholar 

  60. Williams-Herman D, Engel SS, Round E, et al. Safety and tolerability of sitagliptin in clinical studies: a pooled analysis of data from 10,246 patients with type 2 diabetes. BMC Endocr Disord. 2010;10:7.

    Article  PubMed  Google Scholar 

  61. Chan JC, Scott R, Arjona Ferreira JC, et al. Safety and efficacy of sitagliptin in patients with type 2 diabetes and chronic renal insufficiency. Diabetes Obes Metab. 2008;10:545–555.

    Article  PubMed  CAS  Google Scholar 

  62. Doucet J, Chacra A, Maheux P, et al. Efficacy and safety of saxagliptin in older patients with type 2 diabetes mellitus. Curr Med Res Opin. 2011;27:863–89.

    Article  PubMed  CAS  Google Scholar 

  63. ClinicalTrials.gov. Saxagliptin compared to glimepiride in elderly type 2 diabetes patients, with inadequate glycemic control on metformin (GENERATION) Available at: http://clinicaltrials.gov/ct2/show/NCT01006603. Accessed Jan 10 2011.

  64. Nowicki M, Rychlik I, Haller H, et al. Long-term treatment with the dipeptidyl peptidase-4 inhibitor saxagliptin in patients with type 2 diabetes mellitus and renal impairment: a randomized controlled 52-week efficacy and safety study. Int J Clin Pract. 2011;65:1230–1239.

    Article  PubMed  CAS  Google Scholar 

  65. Scott LJ. Alogliptin: a review of its use in the management of type 2 diabetes mellitus. Drugs. 2010;70:2051–2072.

    Article  PubMed  CAS  Google Scholar 

  66. Pratley RE, McCall T, Fleck PR, Wilson CA, Mekki Q. Alogliptin use in elderly people: a pooled analysis from phase 2 and 3 studies. J Am Geriatr Soc. 2009;57:2011–2019.

    Article  PubMed  Google Scholar 

  67. Scott, Lesley J. Drugs: Alogliptin: a review of its use in the management of type 2 diabetes mellitus. Drugs. 2010;70:2051–2072.

    Article  PubMed  CAS  Google Scholar 

  68. Deacon CF, Holst JJ. Linagliptin, a xanthine-based dipeptidyl peptidase-4 inhibitor with an unusual profile for the treatment of type 2 diabetes. Exp Opin Investig Drugs. 2010;19:133–140.

    Article  CAS  Google Scholar 

  69. ClinicalTrials.gov. Efficacy and safety of linagliptin in elderly patients with type 2 diabetes. Available at: http://clinicaltrials.gov/ct2/show/NCT01084005. Accessed Jan 12 2011.

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Authors and Affiliations

  1. Department of Geriatric Medicine and Metabolic Diseases, Second University of Naples, Naples, Italy

    Giuseppe Paolisso, Raffaele Marfella & Maria Rosaria Rizzo

  2. Geriatric Cardiology and Medicine, Careggi Teaching Hospital, Florence, Italy

    Matteo Monami

  3. Diabetes Agency, Careggi Teaching Hospital, Florence, Italy

    Edoardo Mannucci

  4. VI Division of Internal Medicine, Piazza Miraglia 2, 80138, Napoli, Italy

    Giuseppe Paolisso

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  1. Giuseppe Paolisso
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  2. Matteo Monami
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  3. Raffaele Marfella
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  4. Maria Rosaria Rizzo
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  5. Edoardo Mannucci
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Correspondence to Giuseppe Paolisso.

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Paolisso, G., Monami, M., Marfella, R. et al. Dipeptidyl Peptidase-4 Inhibitors in the Elderly: More Benefits or Risks?. Adv Therapy 29, 218–233 (2012). https://doi.org/10.1007/s12325-012-0008-x

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