Applied Evidence
Diabetes in the elderly: Matching meds to needs
J Fam Pract. 2018 July;67(7):408-410,412-415
Hofstra Northwell School of Medicine, Northwell Health, Glen Cove, NY
bkeber@northwell.edu
The authors reported no potential conflict of interest relevant to this article.
From The Journal of Family Practice | 2018;67(7):408-410,412-415.
1. CDC. National Diabetes Statistics Report: Estimates of Diabetes and Its Burden in the United States, 2017. Atlanta, GA, U.S. Department of Health and Human Services, 2017.
2. Lee PG, Halter JB. The pathophysiology of hyperglycemia in older adults: clinical considerations. Diabetes Care. 2017;40:444-452.
3. American Diabetes Association. Standards of medical care in diabetes—2017. Diabetes Care. 2017;40(Suppl 1):S1–S138.
4. Garber AJ, Abrahamson MJ, Barzilay JI, et al. Consensus statement by the American Association of Clinical Endocrinologists and American College of Endocrinology on the comprehensive type 2 diabetes management algorithm—2017 Executive Summary. Endocr Pract. 2017;23:207–238.
5. Holman RR, Paul SK, Bethel MA, et al. 10-year follow-up of intensive glucose control in type 2 diabetes. N Engl J Med. 2008;359:1577-1589.
6. Kezerle L, Shalev L, Barski L. Treating the elderly diabetic patient: special considerations. Diabetes Metab Syndr Obes. 2014;7:391-400.
7. Singh J, Tushar B. Metformin use and vitamin B12 deficiency in patients with type-2 diabetes mellitus. MVP J Med Sci. 2016:3:67-70.
8. Fravel MA, McDanel DL, Ross MB, et al. Special considerations for treatment of type 2 diabetes mellitus in the elderly. Am J Health Syst Pharm. 2011;68:500-509.
9. Hanlon JT, Semla TP, Schmader KE. Alternative medications for medications in the use of high-risk medications in the elderly and potentially harmful drug-disease interactions in the elderly quality measures. J Am Geriatr Soc. 2015;63:e8–e18.
10. American Geriatrics Society 2015 Beers Criteria Update Expert Panel. American Geriatrics Society 2015 updated Beers criteria for potentially inappropriate medication use in older adults. J Am Geriatr Soc. 2015;63:2227-2246.
11. Schernthaner G, Curie CJ, Schernthaner GH. Do we still need pioglitazone for the treatment of type 2 diabetes? A risk-benefit critique in 2013. Diabetes Care. 2013;36(Suppl 2):S155-S161.
12. Lewis JD, Ferrara A, Peng T, et al. Risk of bladder cancer among diabetic patients treated with pioglitazone: interim report of a longitudinal cohort study. Diabetes Care. 2011;34:916-922.
13. Avogaro A, Dardano A, de Kreutzenberg SV, et al. Dipeptidyl peptidase-4 inhibitors can minimize the hypoglycaemic burden and enhance safety in elderly people with diabetes. Diabetes Obes Metab. 2015;17:107-115.
14. DeVries JH, RosenstocK J. DPP-4 inhibitor-related pancreatitis: rare but real! Diabetes Care. 2017;40:161-163.
15. Leiter LA, Teoh H, Braunwald E, et al. Efficacy and safety of saxagliptin in older participants in the SAVOR-TIMI 53 trial. Diabetes Care. 2015;38:1145-1153.
16. White WB, Bakris GL, Bergenstal RM, et al. EXamination of cArdiovascular outcoMes with alogliptIN versus standard of carE in patients with type 2 diabetes mellitus and acute coronary syndrome (EXAMINE): a cardiovascular safety study of the dipeptidyl peptidase 4 inhibitor alogliptin in patients with type 2 diabetes with acute coronary syndrome. Am Heart J. 2011;162:620-626.
17. Raccah D, Miossec P, Esposito V, et al. Efficacy and safety of lixisenatide in elderly (≥65 years old) and very elderly (≥75 years old) patients with type 2 diabetes: an analysis from the GetGoal phase III programme. Diabetes Metab Res Rev. 2015;31:204-211.
18. Marso SP, Bain SC, Consoli A, et al; SUSTAIN-6 investigators. Semaglutide and cardiovascular outcomes in patients with type 2 diabetes. N Engl J Med. 2016;375:1834-1844.
19. Marso SP, Daniels GH, Brown-Frandsen K, et al; LEADER Steering Committee, LEADER Trial Investigators. Liraglutide and cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2016;375:311-322.
20. Lusk KA, Barnes NE. Role of sodium-glucose cotransporter 2 (SGLT2) inhibitors. US Pharm. 2016;41:26-29.
21. U.S. Food and Drug Administration. Sodium-glucose cotransporter-2 (SGLT2) inhibitors. Available at: https://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm446852.htm. Accessed May 18, 2018.
22. Miller EM. Overview of the efficacy and safety of SGLT-2 inhibitors in type 2 diabetes mellitus. J Fam Pract. 2017;66(2 Suppl):S5-S12.
23. Zinman B, Wanner C, Lachin JM, et al. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med. 2015;373:2117-2128.
24. Owens DR. Clinical evidence for the earlier initiation of insulin therapy in type 2 diabetes. Diabetes Technol Ther. 2013;15:776-785.
25. Papa G, Fedele V, Chiavetta A, et al. Therapeutic options for elderly diabetic subjects: open label, randomized clinical trial of insulin glargine added to oral antidiabetic drugs versus increased dosage of oral antidiabetic drugs. Acta Diabetol. 2008;45:53-59.
26. Fu H, Xie W, Curtis B, et al. Identifying factors associated with hypoglycemia-related hospitalizations among elderly patients with T2DM in the US: a novel approach using influential variable analysis. Curr Med Res Opin. 2014;30:1787-1793.
27. Sorli C, Warren M, Oyer D, et al. Elderly patients with diabetes experience a lower rate of nocturnal hypoglycaemia with insulin degludec than with insulin glargine: a meta-analysis of phase IIIa trials. Drugs Aging. 2013;30:1009-1018.
28. Sampanis CH. Management of hyperglycemia in patients with diabetes mellitus and chronic renal failure. Hippokratia. 2008;12:22-27.
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Sodium glucose cotransporter-2 inhibitors
SGLT-2 inhibitors prevent the reabsorption of renal-filtered glucose, resulting in decreased blood glucose levels and increased urinary excretion of glucose without stimulating insulin secretion, and therefore without increasing the risk of hypoglycemia. Additional effects include decreased blood pressure and weight loss.20 Dose adjustment is required in renal impairment.
SGLT-2 inhibitors can be used as monotherapy or in combination with other agents, including insulin, and the relatively low risk of hypoglycemia and moderate A1C lowering potential of 0.5% to 1% provide an oral option for select older patients.20 Common adverse events include hypotension, hyperkalemia, increased low-density lipoprotein (LDL) levels, acute kidney injury, genital mycotic infections, and hypoglycemia when used in combination with insulin or insulin secretagogues.20
DPP-4 agents are ideal for older patients who are not candidates for metformin or a sulfonylurea.
Additional warnings have been issued by the FDA for the risk of urinary tract infection with sepsis, as well as diabetic ketoacidosis associated with SGLT-2 inhibitor use.21 The FDA has reported bone fracture risk and decreased bone mineral density with canagliflozin.21 Avoid using SGLT-2 inhibitors in patients with osteopenia or osteoporosis, as the risks outweigh the benefits. Drug-specific warnings may further impact individual use of an agent, with canagliflozin most recently having been associated with increased risk of leg and foot amputations.21
Given the adverse effect profile of SGLT-2 inhibitors, assess their risks and benefits in older patients on a case-by-case basis. Before initiating therapy, evaluate each patient's volume status. A higher incidence of adverse effects related to intravascular volume depletion has been reported in those 65 or older, with a more prominent increase seen in patients 75 or older.22 However, the risk of hypoglycemia does not seem to increase with age.22
Although many adverse effects have been reported with SGLT-2 inhibitors, empagliflozin was associated with significantly lower rates of all-cause and cardiovascular death and lower risk of hospitalization for heart failure in the only SGLT-2 inhibitor cardiovascular outcomes trial reported to date.23 If this cardiovascular benefit is replicated in additional trials of the other SGLT-2 inhibitors, use of this drug class may increase.
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