Abstract
The prevalence of type 2 diabetes mellitus (T2DM) is expected to increase in the geriatric group with increasing incidence of diabetes with aging and improved life expectancy. Therefore, effective and safe treatment of older T2DM patients is becoming more important in clinical practice. The elderly show heterogeneous individual functional status, and some may have physical handicaps, visual defects, cognitive dysfunction, or psychological disorders such as depression. Therefore, individual approaches depending on presence and progression of geriatric syndromes, comorbidities, and risk of hypoglycemia are important in pharmacological treatment of T2DM in older patients.
REFERENCES
1. Korean Diabetes Association. Diabetes fact sheet in Korea 2018. Available from:. http://www.diabetes.or.kr/pro/news/admin.php?category=A&code=admin&number=1615&mode=view. (updated 2018 Oct 8).
2. Alagiakrishnan K, Sclater A. Psychiatric disorders presenting in the elderly with type 2 diabetes mellitus. Am J Geriatr Psychiatry. 2012; 20:645–52.
3. Ponticelli C, Sala G, Glassock RJ. Drug management in the elderly adult with chronic kidney disease: a review for the primary care physician. Mayo Clin Proc. 2015; 90:633–45.
4. Korean Diabetes Association. Treatment guideline for diabetes, 2019. Available from:. http://www.diabetes.or.kr/pro/publish/guide.php?code=guide&mode=view&number=735. (update 2019 Jun 21).
5. Wong CW. Avoiding hypoglycaemia: a new target of care for elderly diabetic patients. Hong Kong Med J. 2015; 21:444–54.
6. Lipska KJ, Ross JS, Wang Y, Inzucchi SE, Minges K, Karter AJ, Huang ES, Desai MM, Gill TM, Krumholz HM. National trends in US hospital admissions for hyperglycemia and hypoglycemia among Medicare beneficiaries, 1999 to 2011. JAMA Intern Med. 2014; 174:1116–24.
7. Yang SW, Park KH, Zhou YJ. The impact of hypoglycemia on the cardiovascular system: physiology and pathophysiology. Angiology. 2016; 67:802–9.
8. Zhao Y, Kachroo S, Kawabata H, Colilla S, Mukherjee J, Fonseca V, Iloeje U, Shi L. Association between hypoglycemia and fall-related fractures and health care utilization in older veterans with type 2 diabetes. Endocr Pract. 2016; 22:196–204.
9. Diabetes Canada Clinical Practice Guidelines Expert Committee. Meneilly GS, Knip A, Miller DB, Sherifali D, Tessier D, Zahedi A. Diabetes in older people. Can J Diabetes. 2018; 42(Suppl 1):S283–95.
10. Reinstatler L, Qi YP, Williamson RS, Garn JV, Oakley GP Jr. Association of biochemical B₁₂ deficiency with metformin therapy and vitamin B₁₂ supplements: the National Health and Nutrition Examination Survey, 1999-2006. Diabetes Care. 2012; 35:327–33.
11. Leung S, Mattman A, Snyder F, Kassam R, Meneilly G, Nexo E. Metformin induces reductions in plasma cobalamin and haptocorrin bound cobalamin levels in elderly diabetic patients. Clin Biochem. 2010; 43:759–60.
12. Kahn SE, Haffner SM, Heise MA, Herman WH, Holman RR, Jones NP, Kravitz BG, Lachin JM, O\'Neill MC, Zinman B, Viberti G; ADOPT Study Group. Glycemic durability of rosiglitazone, metformin, or glyburide monotherapy. N Engl J Med. 2006; 355:2427–43.
13. Loke YK, Singh S, Furberg CD. Long-term use of thiazolidinediones and fractures in type 2 diabetes: a metaanalysis. CMAJ. 2009; 180:32–9.
14. Schwartz AV, Chen H, Ambrosius WT, Sood A, Josse RG, Bonds DE, Schnall AM, Vittinghoff E, Bauer DC, Banerji MA, Cohen RM, Hamilton BP, Isakova T, Sellmeyer DE, Simmons DL, Shibli-Rahhal A, Williamson JD, Margolis KL. Effects of TZD use and discontinuation on fracture rates in ACCORD bone study. J Clin Endocrinol Metab. 2015; 100:4059–66.
15. Shorr RI, Ray WA, Daugherty JR, Griffin MR. Individual sulfonylureas and serious hypoglycemia in older people. J Am Geriatr Soc. 1996; 44:751–5.
16. Greco D, Pisciotta M, Gambina F, Maggio F. Severe hypoglycaemia leading to hospital admission in type 2 diabetic patients aged 80 years or older. Exp Clin Endocrinol Diabetes. 2010; 118:215–9.
17. Schernthaner G, Grimaldi A, Di Mario U, Drzewoski J, Kempler P, Kvapil M, Novials A, Rottiers R, Rutten GE, Shaw KM. GUIDE study: double-blind comparison of once-daily gliclazide MR and glimepiride in type 2 diabetic patients. Eur J Clin Invest. 2004; 34:535–42.
18. Del Prato S, Heine RJ, Keilson L, Guitard C, Shen SG, Emmons RP. Treatment of patients over 64 years of age with type 2 diabetes: experience from nateglinide pooled database retrospective analysis. Diabetes Care. 2003; 26:2075–80.
19. Papa G, Fedele V, Rizzo MR, Fioravanti M, Leotta C, Solerte SB, Purrello F, Paolisso G. Safety of type 2 diabetes treatment with repaglinide compared with glibenclamide in elderly people: a randomized, open-label, two-period, crossover trial. Diabetes Care. 2006; 29:1918–20.
20. Schernthaner G, Barnett AH, Patel S, Hehnke U, von Eynatten M, Woerle HJ. Safety and efficacy of the dipeptidyl peptidase-4 inhibitor linagliptin in elderly patients with type 2 diabetes: a comprehensive analysis of data from 1331 individuals aged ≥65 years. Diabetes Obes Metab. 2014; 16:1078–86.
21. Round EM, Engel SS, Golm GT, Davies MJ, Kaufman KD, Goldstein BJ. Safety of sitagliptin in elderly patients with type 2 diabetes: a pooled analysis of 25 clinical studies. Drugs Aging. 2014; 31:203–14.
22. Karyekar CS, Ravichandran S, Allen E, Fleming D, Frederich R. Tolerability and efficacy of glycemic control with saxagliptin in older patients (aged ≥65 years) with inadequately controlled type 2 diabetes mellitus. Clin Interv Aging. 2013; 8:419–30.
23. Schwartz SL. Treatment of elderly patients with type 2 diabetes mellitus: a systematic review of the benefits and risks of dipeptidyl peptidase-4 inhibitors. Am J Geriatr Pharmacother. 2010; 8:405–18.
24. Leiter LA, Teoh H, Braunwald E, Mosenzon O, Cahn A, Kumar KM, Smahelova A, Hirshberg B, Stahre C, Frederich R, Bonnici F, Scirica BM, Bhatt DL, Raz I; SAVOR-TIMI 53 Steering Committee and Investigators. Efficacy and safety of saxagliptin in older participants in the SAVOR-TIMI 53 trial. Diabetes Care. 2015; 38:1145–53.
25. Bode BW, Brett J, Falahati A, Pratley RE. Comparison of the efficacy and tolerability profile of liraglutide, a once-daily human GLP-1 analog, in patients with type 2 diabetes ≥65 and <65 years of age: a pooled analysis from phase III studies. Am J Geriatr Pharmacother. 2011; 9:423–33.
26. Boustani MA, Pittman I 4th, Yu M, Thieu VT, Varnado OJ, Juneja R. Similar efficacy and safety of once-weekly dulaglutide in patients with type 2 diabetes aged ≥65 and <65 years. Diabetes Obes Metab. 2016; 18:820–8.
27. Meneilly GS, Roy-Duval C, Alawi H, Dailey G, Bellido D, Trescoli C, Manrique Hurtado H, Guo H, Pilorget V, Perfetti R, Simpson H; GetGoal-O Trial Investigators. Lixisenatide therapy in older patients with type 2 diabetes inadequately controlled on their current antidiabetic treatment: the GetGoal-O randomized trial. Diabetes Care. 2017; 40:485–93.
28. Marso SP, Daniels GH, Brown-Frandsen K, Kristensen P, Mann JF, Nauck MA, Nissen SE, Pocock S, Poulter NR, Ravn LS, Steinberg WM, Stockner M, Zinman B, Bergenstal RM, Buse JB; LEADER Steering Committee; LEADER Trial Investigators. Liraglutide and cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2016; 375:311–22.
29. Marso SP, Bain SC, Consoli A, Eliaschewitz FG, Jódar E, Leiter LA, Lingvay I, Rosenstock J, Seufert J, Warren ML, Woo V, Hansen O, Holst AG, Pettersson J, Vilsbøll T; SUSTAIN-6 Investigators. Semaglutide and cardiovascular outcomes in patients with type 2 diabetes. N Engl J Med. 2016; 375:1834–44.
30. Johnston PS, Lebovitz HE, Coniff RF, Simonson DC, Raskin P, Munera CL. Advantages of alpha-glucosidase inhibition as monotherapy in elderly type 2 diabetic patients. J Clin Endocrinol Metab. 1998; 83:1515–22.
31. Josse RG, Chiasson JL, Ryan EA, Lau DC, Ross SA, Yale JF, Leiter LA, Maheux P, Tessier D, Wolever TM, Gerstein H, Rodger NW, Dornan JM, Murphy LJ, Rabasa-Lhoret R, Meneilly GS. Acarbose in the treatment of elderly patients with type 2 diabetes. Diabetes Res Clin Pract. 2003; 59:37–42.
32. Sinclair AJ, Bode B, Harris S, Vijapurkar U, Shaw W, Desai M, Meininger G. Efficacy and safety of canagliflozin in individuals aged 75 and older with type 2 diabetes mellitus: a pooled analysis. J Am Geriatr Soc. 2016; 64:543–52.
33. Wanner C, Inzucchi SE, Lachin JM, Fitchett D, von Eynatten M, Mattheus M, Johansen OE, Woerle HJ, Broedl UC, Zinman B; EMPA-REG OUTCOME Investigators. Empagliflozin and progression of kidney disease in type 2 diabetes. N Engl J Med. 2016; 375:323–34.
34. Fioretto P, Mansfield TA, Ptaszynska A, Yavin Y, Johnsson E, Parikh S. Long-term safety of dapagliflozin in older patients with type 2 diabetes mellitus: a pooled analysis of phase IIb/III studies. Drugs Aging. 2016; 33:511–22.
35. Zinman B, Wanner C, Lachin JM, Fitchett D, Bluhmki E, Hantel S, Mattheus M, Devins T, Johansen OE, Woerle HJ, Broedl UC, Inzucchi SE; EMPA-REG OUTCOME Investigators. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med. 2015; 373:2117–28.
36. Erondu N, Desai M, Ways K, Meininger G. Diabetic ketoacidosis and related events in the canagliflozin type 2 diabetes clinical program. Diabetes Care. 2015; 38:1680–6.
37. Peters AL, Buschur EO, Buse JB, Cohan P, Diner JC, Hirsch IB. Euglycemic diabetic ketoacidosis: a potential complication of treatment with sodium-glucose cotransporter 2 inhibition. Diabetes Care. 2015; 38:1687–93.
38. Trimble LA, Sundberg S, Markham L, Janicijevic S, Beattie BL, Meneilly GS. Value of the clock drawing test to predict problems with insulin skills in older adults. Can J Diabetes. 2005; 29:102–4.
39. Zeyfang A, Berndt S, Aurnhammer G, Nikolaus T, Oster P, Bahrmann A. A short easy test can detect ability for autonomous insulin injection by the elderly with diabetes mellitus. J Am Med Dir Assoc. 2012; 13:81.e15–8.
40. Ritzel R, Roussel R, Bolli GB, Vinet L, Brulle-Wohlhueter C, Glezer S, YkiJärvinen H. Patient-level metaanalysis of the EDITION 1, 2 and 3 studies: glycaemic control and hypoglycaemia with new insulin glargine 300 U/ml versus glargine 100 U/ml in people with type 2 diabetes. Diabetes Obes Metab. 2015; 17:859–67.