Applied Evidence

Diabetes in the elderly: Matching meds to needs

J Fam Pract. 2018 July;67(7):408-410,412-415

From The Journal of Family Practice | 2018;67(7):408-410,412-415.

References

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.

29. Corsi A, Torre E, Coronel GA, et al. Pre-filled insulin pen in newly insulin-treated diabetic patients over 60 years old. Diab Nutr Metab. 1997;10:78-81.

30. Coscelli C, Calabrese G, Fedele D, et al. Use of premixed insulin among the elderly. Reduction of errors in patient preparation of mixtures. Diabetes Care. 1992;15:1628-1630.

31. American Geriatrics Society. Ten things clinicians and patients should question. Available at: http://www.choosingwisely.org/societies/american-geriatrics-society/. Accessed May 18, 2018.

32. Mogensen UM, Andersson C, Fosbøl EL, et al. Sulfonylurea in combination with insulin is associated with increased mortality compared with a combination of insulin and metformin in a retrospective Danish nationwide study. Diabetologia. 2015;58:50-58.

DPP-4 inhibitors

Dipeptidyl peptidase-4 (DPP-4) inhibitors work by suppressing the enzyme that degrades 2 incretin hormones, glucagon-like peptide 1 (GLP-1) and gastric inhibitory polypeptide (GIP). The resulting enhancement of incretin activity increases glucose-dependent insulin secretion, decreases glucagon secretion, and promotes satiety.⁶ These agents have modest efficacy with the potential to lower A1C by 0.5% to 0.9%.^8,13 Studies show that DPP-4 inhibitors are well tolerated with a minimal risk of hypoglycemia in the elderly.¹³ These agents are ideal for combination therapy or for monotherapy in older patients who are not good candidates for metformin or a sulfonylurea.

The safety profile, neutral effect on weight, and once-daily dosing make these agents advantageous for use in frail and debilitated elderly patients, as well as in patients with cognitive dysfunction, decreased dexterity, inconsistent meal patterns, or adherence issues. Dose adjustment is required in renal impairment, with the exception of linagliptin. High cost or formulary restrictions may impact use of these agents.

The DPP-4 inhibitors were well tolerated in short-term studies, but long-term safety has yet to be established.⁶ Reported post-marketing adverse effects include acute renal failure, allergic reactions, and acute pancreatitis.^6,14 These agents should be avoided in any patient with a history of pancreatitis.¹⁴ In addition, trials investigating the cardiovascular safety and efficacy of DPP-4 inhibitors point to an increased risk of heart failure with the use of saxagliptin and alogliptin, regardless of age.^15,16 The potential for adverse effects warrants increased patient monitoring when using these agents in older patients.

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are injectable agents that potentiate the actions of the naturally occurring incretin GLP-1, which increases glucose-dependent insulin secretion, inhibits glucagon release, reduces hepatic glucose production, and delays gastric emptying. These agents have a pronounced effect on satiety and promote weight loss. The most common adverse effects are nausea, vomiting, and diarrhea, which occur most commonly during treatment initiation and titration. Studies in elderly patients confirm A1C reductions of 1% to 1.5% and a low risk of hypoglycemia when used alone.^17,18

GLP-1 RAs can be used as monotherapy in older patients at risk for hypoglycemia or in those with hypoglycemic unawareness. They can also be used in combination therapy with other agents, including insulin, though concomitant use with insulin or insulin secretagogues increases the risk of hypoglycemia.³ Weight loss and GI adverse effects may limit the use of these agents in frail or undernourished elderly patients.⁶

Continue to: Since these agents are injected...