Abstract
The increasing incidence of type 2 diabetes in the general population as well as enhanced life expectancy has resulted in a rapid rise in the prevalence of diabetes in the older population. Diabetes causes significant morbidity and impairs quality of life. Managing diabetes in older adults is a daunting task due to unique health and psychosocial challenges. Medical management is complicated by polypharmacy, cognitive impairment, urinary incontinence, injurious falls, and persistent pain. Health care providers now have several traditional and contemporary pharmacologic agents to manage diabetes. Avoidance of hypoglycemia is critical; however, evidence-based guidelines are lacking due to the paucity of clinical trials in older adults. For many in this population, maintaining independence is more important than adherence to published guidelines to prevent diabetes complications. The goal of diabetes care in older adults is to enhance the quality of life without subjecting these patients to intrusive and complicated interventions. Recent technological advancements such as continuous glucose monitoring systems can have crucial supplementary benefits in the geriatric population.
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References
National diabetes statistics report 2020. Estimates of diabetes incidence and its burden in the United States. 2020. Available from: https://www.cdc.gov/diabetes/pdfs/data/statistics/national-diabetes-statistics-report.pdf.
Sinclair A, Saeedi P, Kaundal A, Karuranga S, Malanda B, Williams R. Diabetes and global ageing among 65–99-year-old adults: findings from the International Diabetes Federation Diabetes Atlas, 9th edition. Diabetes Res Clin Pract. 2020;162:108078.
Kirkman MS, Briscoe VJ, Clark N, Florez H, Haas LB, Halter JB, et al. Diabetes in older adults: a consensus report. J Am Geriatr Soc. 2012;60(12):2342–56.
Diagnosis and classification of diabetes mellitus. Diabetes Care. 2006;29(Suppl 1):S43–8.
Lee PG, Halter JB. The pathophysiology of hyperglycemia in older adults: clinical considerations. Diabetes Care. 2017;40(4):444–52.
Mordarska K, Godziejewska-Zawada M. Diabetes in the elderly. Prz Menopauzalny. 2017;16(2):38–43.
Barbieri M, Rizzo MR, Manzella D, Grella R, Ragno E, Carbonella M, et al. Glucose regulation and oxidative stress in healthy centenarians. Exp Gerontol. 2003;38(1–2):137–43.
Basu R, Breda E, Oberg AL, Powell CC, Dalla Man C, Basu A, et al. Mechanisms of the age-associated deterioration in glucose tolerance: contribution of alterations in insulin secretion, action, and clearance. Diabetes. 2003;52(7):1738–48.
Szoke E, Shrayyef MZ, Messing S, Woerle HJ, van Haeften TW, Meyer C, et al. Effect of aging on glucose homeostasis: accelerated deterioration of beta-cell function in individuals with impaired glucose tolerance. Diabetes Care. 2008;31(3):539–43.
Giddings SJ, Carnaghi LR, Mooradian AD. Age-related changes in pancreatic islet cell gene expression. Metabolism. 1995;44(3):320–4.
McLarty DG, Swai AB, Kitange HM, Masuki G, Mtinangi BL, Kilima PM, et al. Prevalence of diabetes and impaired glucose tolerance in rural Tanzania. Lancet. 1989;1(8643):871–5.
DeFronzo RA. Insulin resistance, lipotoxicity, type 2 diabetes and atherosclerosis: the missing links. The Claude Bernard Lecture 2009. Diabetologia. 2010;53(7):1270–87.
Weinger K, Beverly EA, Smaldone A. Diabetes self-care and the older adult. West J Nurs Res. 2014;36(9):1272–98.
American Diabetes Association. 12. Older Adults: Standards of Medical Care in Diabetes-2021. Diabetes Care. 2021;44(Suppl 1):S168–79.
Moreno G, Mangione CM, Kimbro L, Vaisberg E. Guidelines abstracted from the American Geriatrics Society Guidelines for Improving the Care of Older Adults with Diabetes Mellitus: 2013 update. J Am Geriatr Soc. 2013;61(11):2020–6.
LeRoith D, Biessels GJ, Braithwaite SS, Casanueva FF, Draznin B, Halter JB, et al. Treatment of diabetes in older adults: an endocrine society* clinical practice guideline. J Clin Endocrinol Metab. 2019;104(5):1520–74.
Wong CW, Lee JS, Tam KF, Hung HF, So WY, Shum CK, et al. Diabetes in older people: position statement of The Hong Kong Geriatrics Society and the Hong Kong Society of Endocrinology, Metabolism and Reproduction. Hong Kong Med J. 2017;23(5):524–33.
Blaum C, Cigolle CT, Boyd C, Wolff JL, Tian Z, Langa KM, et al. Clinical complexity in middle-aged and older adults with diabetes: the Health and Retirement Study. Med Care. 2010;48(4):327–34.
Applegate WB, Blass JP, Williams TF. Instruments for the functional assessment of older patients. N Engl J Med. 1990;322(17):1207–14.
Assar ME, Laosa O, Rodríguez ML. Diabetes and frailty. Curr Opin Clin Nutr Metab Care. 2019;22(1):52–7.
Morley JE, Cao L. Rapid screening for sarcopenia. J Cachexia Sarcopenia Muscle. 2015;6(4):312–4.
Munshi M, Grande L, Hayes M, Ayres D, Suhl E, Capelson R, et al. Cognitive dysfunction is associated with poor diabetes control in older adults. Diabetes Care. 2006;29(8):1794–9.
Yaffe K, Falvey CM, Hamilton N, Harris TB, Simonsick EM, Strotmeyer ES, et al. Association between hypoglycemia and dementia in a biracial cohort of older adults with diabetes mellitus. JAMA Intern Med. 2013;173(14):1300–6.
Punthakee Z, Miller ME, Launer LJ, Williamson JD, Lazar RM, Cukierman-Yaffee T, et al. Poor cognitive function and risk of severe hypoglycemia in type 2 diabetes: post hoc epidemiologic analysis of the ACCORD trial. Diabetes Care. 2012;35(4):787–93.
de Galan BE, Zoungas S, Chalmers J, Anderson C, Dufouil C, Pillai A, et al. Cognitive function and risks of cardiovascular disease and hypoglycaemia in patients with type 2 diabetes: the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) trial. Diabetologia. 2009;52(11):2328–36.
Sinclair AJ, Abdelhafiz AH, Rodríguez-Mañas L. Frailty and sarcopenia—newly emerging and high impact complications of diabetes. J Diabetes Complications. 2017;31(9):1465–73.
Kalyani RR, Metter EJ, Egan J, Golden SH, Ferrucci L. Hyperglycemia predicts persistently lower muscle strength with aging. Diabetes Care. 2015;38(1):82–90.
Yoon JW, Ha YC, Kim KM, Moon JH, Choi SH, Lim S, et al. Hyperglycemia is associated with impaired muscle quality in older men with diabetes: the Korean Longitudinal study on health and aging. Diabetes Metab J. 2016;40(2):140–6.
Lee S, Lee S, Harada K, Bae S, Makizako H, Doi T, et al. Relationship between chronic kidney disease with diabetes or hypertension and frailty in community-dwelling Japanese older adults. Geriatr Gerontol Int. 2017;17(10):1527–33.
Castrejón-Pérez RC, Gutiérrez-Robledo LM, Cesari M, Pérez-Zepeda MU. Diabetes mellitus, hypertension and frailty: a population-based, cross-sectional study of Mexican older adults. Geriatr Gerontol Int. 2017;17(6):925–30.
Hasan SS, Mamun AA, Clavarino AM, Kairuz T. Incidence and risk of depression associated with diabetes in adults: evidence from longitudinal studies. Community Ment Health J. 2015;51(2):204–10.
Sinclair AJ, Abdelhafiz AH. Challenges and strategies for diabetes management in community-living older adults. Diabetes Spectr. 2020;33(3):217–27.
Lohman M, Dumenci L, Mezuk B. Depression and frailty in late life: evidence for a common vulnerability. J Gerontol B Psychol Sci Soc Sci. 2016;71(4):630–40.
Soysal P, Veronese N, Thompson T, Kahl KG, Fernandes BS, Prina AM, et al. Relationship between depression and frailty in older adults: a systematic review and meta-analysis. Ageing Res Rev. 2017;36:78–87.
Godin J, Armstrong JJ, Rockwood K, Andrew MK. Dynamics of frailty and cognition after age 50: why it matters that cognitive decline is mostly seen in old age. J Alzheimers Dis. 2017;58(1):231–42.
Liu YC, Meguro K, Nakamura K, Akanuma K, Nakatsuka M, Seki T, et al. Depression and dementia in old-old population: history of depression may be associated with dementia onset. The Tome Project. Front Aging Neurosci. 2017;9:335.
Aichele S, Ghisletta P. Memory deficits precede increases in depressive symptoms in later adulthood. J Gerontol B Psychol Sci Soc Sci. 2019;74(6):943–53.
Afilalo J, Karunananthan S, Eisenberg MJ, Alexander KP, Bergman H. Role of frailty in patients with cardiovascular disease. Am J Cardiol. 2009;103(11):1616–21.
Sakuma K, Yamaguchi A. Sarcopenic obesity and endocrinal adaptation with age. Int J Endocrinol. 2013;2013:204164.
Dichgans M, Leys D. Vascular cognitive impairment. Circ Res. 2017;120(3):573–91.
Dhar AK, Barton DA. Depression and the link with cardiovascular disease. Front Psychiatry. 2016;7:33.
Feil DG, Zhu CW, Sultzer DL. The relationship between cognitive impairment and diabetes self-management in a population-based community sample of older adults with Type 2 diabetes. J Behav Med. 2012;35(2):190–9.
Zoungas S, Patel A, Chalmers J, de Galan BE, Li Q, Billot L, et al. Severe hypoglycemia and risks of vascular events and death. N Engl J Med. 2010;363(15):1410–8.
Ligthelm RJ, Kaiser M, Vora J, Yale JF. Insulin use in elderly adults: risk of hypoglycemia and strategies for care. J Am Geriatr Soc. 2012;60(8):1564–70.
Knowler WC, Barrett-Connor E, Fowler SE, Hamman RF, Lachin JM, Walker EA, et al. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med. 2002;346(6):393–403.
Crandall J, Schade D, Ma Y, Fujimoto WY, Barrett-Connor E, Fowler S, et al. The influence of age on the effects of lifestyle modification and metformin in prevention of diabetes. J Gerontol A Biol Sci Med Sci. 2006;61(10):1075–81.
Adults O. Standards of medical care in diabetes-2018. Diabetes Care. 2018;41(Suppl 1):S119–25.
Kalyani RR, Egan JM. Diabetes and altered glucose metabolism with aging. Endocrinol Metab Clin North Am. 2013;42(2):333–47.
Miller CK, Edwards L, Kissling G, Sanville L. Nutrition education improves metabolic outcomes among older adults with diabetes mellitus: results from a randomized controlled trial. Prev Med. 2002;34(2):252–9.
Wing RR, Bolin P, Brancati FL, Bray GA, Clark JM, Coday M, et al. Cardiovascular effects of intensive lifestyle intervention in type 2 diabetes. N Engl J Med. 2013;369(2):145–54.
Wedick NM, Barrett-Connor E, Knoke JD, Wingard DL. The relationship between weight loss and all-cause mortality in older men and women with and without diabetes mellitus: the Rancho Bernardo study. J Am Geriatr Soc. 2002;50(11):1810–5.
Haas LB. Special considerations for older adults with diabetes residing in skilled nursing facilities. Diabetes Spectr. 2014;27(1):37–43.
Morey MC, Pieper CF, Crowley GM, Sullivan RJ, Puglisi CM. Exercise adherence and 10-year mortality in chronically ill older adults. J Am Geriatr Soc. 2002;50(12):1929–33.
Karani R, McLaughlin MA, Cassel CK. Exercise in the healthy older adult. Am J Geriatr Cardiol. 2001;10(5):269–73.
Inzucchi SE. Is it time to change the type 2 diabetes treatment paradigm? No! metformin should remain the foundation therapy for type 2 diabetes. Diabetes Care. 2017;40(8):1128–32.
Foretz M, Guigas B, Bertrand L, Pollak M, Viollet B. Metformin: from mechanisms of action to therapies. Cell Metab. 2014;20(6):953–66.
Natali A, Ferrannini E. Effects of metformin and thiazolidinediones on suppression of hepatic glucose production and stimulation of glucose uptake in type 2 diabetes: a systematic review. Diabetologia. 2006;49(3):434–41.
Mulherin AJ, Oh AH, Kim H, Grieco A, Lauffer LM, Brubaker PL. Mechanisms underlying metformin-induced secretion of glucagon-like peptide-1 from the intestinal L cell. Endocrinology. 2011;152(12):4610–9.
Miller RA, Chu Q, Xie J, Foretz M, Viollet B, Birnbaum MJ. Biguanides suppress hepatic glucagon signalling by decreasing production of cyclic AMP. Nature. 2013;494(7436):256–60.
Fullerton MD, Galic S, Marcinko K, Sikkema S, Pulinilkunnil T, Chen ZP, et al. Single phosphorylation sites in Acc1 and Acc2 regulate lipid homeostasis and the insulin-sensitizing effects of metformin. Nat Med. 2013;19(12):1649–54.
Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). UK Prospective Diabetes Study (UKPDS) Group. Lancet. 1998;352(9131):854–65.
Hong J, Zhang Y, Lai S, Lv A, Su Q, Dong Y, et al. Effects of metformin versus glipizide on cardiovascular outcomes in patients with type 2 diabetes and coronary artery disease. Diabetes Care. 2013;36(5):1304–11.
Kooy A, de Jager J, Lehert P, Bets D, Wulffelé MG, Donker AJ, et al. Long-term effects of metformin on metabolism and microvascular and macrovascular disease in patients with type 2 diabetes mellitus. Arch Intern Med. 2009;169(6):616–25.
Lazarus B, Wu A, Shin JI, Sang Y, Alexander GC, Secora A, et al. Association of metformin use with risk of lactic acidosis across the range of kidney function: a community-based cohort study. JAMA Intern Med. 2018;178(7):903–10.
Aroda VR, Edelstein SL, Goldberg RB, Knowler WC, Marcovina SM, Orchard TJ, et al. Long-term metformin use and vitamin B12 deficiency in the diabetes prevention program outcomes study. J Clin Endocrinol Metab. 2016;101(4):1754–61.
Qaseem A, Barry MJ, Humphrey LL, Forciea MA. Oral pharmacologic treatment of type 2 diabetes mellitus: a clinical practice guideline update from the American College of Physicians. Ann Intern Med. 2017;166(4):279–90.
Lv W, Wang X, Xu Q, Lu W. Mechanisms and characteristics of sulfonylureas and glinides. Curr Top Med Chem. 2020;20(1):37–56.
Shorr RI, Ray WA, Daugherty JR, Griffin MR. Individual sulfonylureas and serious hypoglycemia in older people. J Am Geriatr Soc. 1996;44(7):751–5.
Rosenkranz B, Profozic V, Metelko Z, Mrzljak V, Lange C, Malerczyk V. Pharmacokinetics and safety of glimepiride at clinically effective doses in diabetic patients with renal impairment. Diabetologia. 1996;39(12):1617–24.
Dills DG, Schneider J. Clinical evaluation of glimepiride versus glyburide in NIDDM in a double-blind comparative study. Glimepiride/Glyburide Research Group. Horm Metab Res. 1996;28(9):426–9.
Horani MH, Mooradian AD. Management of obesity in the elderly: special considerations. Treat Endocrinol. 2002;1(6):387–98.
Schwartz TB, Meinert CL. The UGDP controversy: thirty-four years of contentious ambiguity laid to rest. Perspect Biol Med. 2004;47(4):564–74.
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 (UKPDS) Group. Lancet. 1998;352(9131):837–53.
Vaccaro O, Masulli M, Nicolucci A, Bonora E, Del Prato S, Maggioni AP, et al. Effects on the incidence of cardiovascular events of the addition of pioglitazone versus sulfonylureas in patients with type 2 diabetes inadequately controlled with metformin (TOSCA.IT): a randomised, multicentre trial. Lancet Diabetes Endocrinol. 2017;5(11):887–97.
Balfour JA, Faulds D. Repaglinide. Drugs Aging. 1998;13(2):173–80.
Johansen OE, Birkeland KI. Defining the role of repaglinide in the management of type 2 diabetes mellitus: a review. Am J Cardiovasc Drugs. 2007;7(5):319–35.
Schwarz SL, Gerich JE, Marcellari A, Jean-Louis L, Purkayastha D, Baron MA. Nateglinide, alone or in combination with metformin, is effective and well tolerated in treatment-naïve elderly patients with type 2 diabetes. Diabetes Obes Metab. 2008;10(8):652–60.
Omori K, Nomoto H, Nakamura A, Takase T, Cho KY, Ono K, et al. Reduction in glucose fluctuations in elderly patients with type 2 diabetes using repaglinide: a randomized controlled trial of repaglinide vs sulfonylurea. J Diabetes Investig. 2019;10(2):367–74.
Mooradian AD, Chehade J, Thurman JE. The role of thiazolidinediones in the treatment of patients with type 2 diabetes mellitus. Treat Endocrinol. 2002;1(1):13–20.
Nissen SE, Wolski K. Effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes. N Engl J Med. 2007;356(24):2457–71.
Home PD, Pocock SJ, Beck-Nielsen H, Curtis PS, Gomis R, Hanefeld M, et al. Rosiglitazone evaluated for cardiovascular outcomes in oral agent combination therapy for type 2 diabetes (RECORD): a multicentre, randomised, open-label trial. Lancet. 2009;373(9681):2125–35.
Damluji AA, Cohen ER, Moscucci M, Myerburg RJ, Cohen MG, Brooks MM, et al. Insulin provision therapy and mortality in older adults with diabetes mellitus and stable ischemic heart disease: insights from BARI-2D trial. Int J Cardiol. 2017;15(241):35–40.
Kernan WN, Viscoli CM, Furie KL, Young LH, Inzucchi SE, Gorman M, et al. Pioglitazone after ischemic stroke or transient ischemic attack. N Engl J Med. 2016;374(14):1321–31.
Dormandy JA, Charbonnel B, Eckland DJ, Erdmann E, Massi-Benedetti M, Moules IK, et al. Secondary prevention of macrovascular events in patients with type 2 diabetes in the PROactive Study (PROspective pioglitAzone Clinical Trial In macroVascular Events): a randomised controlled trial. Lancet. 2005;366(9493):1279–89.
Aubert RE, Herrera V, Chen W, Haffner SM, Pendergrass M. Rosiglitazone and pioglitazone increase fracture risk in women and men with type 2 diabetes. Diabetes Obes Metab. 2010;12(8):716–21.
Hedrington MS, Davis SN. Considerations when using alpha-glucosidase inhibitors in the treatment of type 2 diabetes. Expert Opin Pharmacother. 2019;20(18):2229–35.
Chiasson JL, Josse RG, Gomis R, Hanefeld M, Karasik A, Laakso M. Acarbose treatment and the risk of cardiovascular disease and hypertension in patients with impaired glucose tolerance: the STOP-NIDDM trial. JAMA. 2003;290(4):486–94.
Coleman RL, Scott CAB, Lang Z, Bethel MA, Tuomilehto J, Holman RR. Meta-analysis of the impact of alpha-glucosidase inhibitors on incident diabetes and cardiovascular outcomes. Cardiovasc Diabetol. 2019;18(1):135.
Josse RG, Chiasson JL, Ryan EA, Lau DC, Ross SA, Yale JF, et al. Acarbose in the treatment of elderly patients with type 2 diabetes. Diabetes Res Clin Pract. 2003;59(1):37–42.
Mooradian AD, Albert SG, Wittry S, Chehade J, Kim J, Bellrichard B. Dose-response profile of acarbose in older subjects with type 2 diabetes. Am J Med Sci. 2000;319(5):334–7.
Gandhi GY, Mooradian AD. Clinical considerations for insulin therapy in older adults with type 1 diabetes. Drugs Aging. 2021. https://doi.org/10.1007/s40266-021-00900-3 (Epub 19 Oct 2021).
Zammitt NN, Frier BM. Hypoglycemia in type 2 diabetes: pathophysiology, frequency, and effects of different treatment modalities. Diabetes Care. 2005;28(12):2948–61.
Abdelhafiz AH, Rodríguez-Mañas L, Morley JE, Sinclair AJ. Hypoglycemia in older people—a less well recognized risk factor for frailty. Aging Dis. 2015;6(2):156–67.
Munshi MN, Slyne C, Segal AR, Saul N, Lyons C, Weinger K. Simplification of insulin regimen in older adults and risk of hypoglycemia. JAMA Intern Med. 2016;176(7):1023–5.
Leung E, Wongrakpanich S, Munshi MN. Diabetes management in the elderly. Diabetes Spectr. 2018;31(3):245–53.
Munshi MN, Pandya N, Umpierrez GE, DiGenio A, Zhou R, Riddle MC. Contributions of basal and prandial hyperglycemia to total hyperglycemia in older and younger adults with type 2 diabetes mellitus. J Am Geriatr Soc. 2013;61(4):535–41.
Pasquel FJ, Powell W, Peng L, Johnson TM, Sadeghi-Yarandi S, Newton C, et al. A randomized controlled trial comparing treatment with oral agents and basal insulin in elderly patients with type 2 diabetes in long-term care facilities. BMJ Open Diabetes Res Care. 2015;3(1):e000104.
Oiknine R, Bernbaum M, Mooradian AD. A critical appraisal of the role of insulin analogues in the management of diabetes mellitus. Drugs. 2005;65(3):325–40.
Janka HU, Plewe G, Busch K. Combination of oral antidiabetic agents with basal insulin versus premixed insulin alone in randomized elderly patients with type 2 diabetes mellitus. J Am Geriatr Soc. 2007;55(2):182–8.
Reznik Y, Cohen O, Aronson R, Conget I, Runzis S, Castaneda J, et al. Insulin pump treatment compared with multiple daily injections for treatment of type 2 diabetes (OpT2mise): a randomised open-label controlled trial. Lancet. 2014;384(9950):1265–72.
Herman WH, Ilag LL, Johnson SL, Martin CL, Sinding J, Al Harthi A, et al. A clinical trial of continuous subcutaneous insulin infusion versus multiple daily injections in older adults with type 2 diabetes. Diabetes Care. 2005;28(7):1568–73.
Stephens EA, Heffner J. Evaluating older patients with diabetes for insulin pump therapy. Diabetes Technol Ther. 2010;12(Suppl 1):S91–7.
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(9548):1696–705.
Pham H, Marathe CS, Phillips LK, Trahair LG, Hatzinikolas S, Huynh L, et al. Longitudinal changes in fasting and glucose-stimulated GLP-1 and GIP in healthy older subjects. J Clin Endocrinol Metab. 2019;104(12):6201–6.
Neumiller JJ. Incretin-based therapies. Med Clin North Am. 2015;99(1):107–29.
Li L, Shen J, Bala MM, Busse JW, Ebrahim S, Vandvik PO, et al. Incretin treatment and risk of pancreatitis in patients with type 2 diabetes mellitus: systematic review and meta-analysis of randomised and non-randomised studies. BMJ. 2014;348:g2366.
Thomsen RW, Pedersen L, Møller N, Kahlert J, Beck-Nielsen H, Sørensen HT. Incretin-based therapy and risk of acute pancreatitis: a nationwide population-based case-control study. Diabetes Care. 2015;38(6):1089–98.
Pencek R, Blickensderfer A, Li Y, Brunell SC, Anderson PW. Exenatide twice daily: analysis of effectiveness and safety data stratified by age, sex, race, duration of diabetes, and body mass index. Postgrad Med. 2012;124(4):21–32.
Marso SP, Daniels GH, Brown-Frandsen K, Kristensen P, Mann JF, Nauck MA, et al. Liraglutide and cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2016;375(4):311–22.
Marso SP, Bain SC, Consoli A, Eliaschewitz FG, Jódar E, Leiter LA, et al. Semaglutide and cardiovascular outcomes in patients with type 2 diabetes. N Engl J Med. 2016;375(19):1834–44.
Gerstein HC, Colhoun HM, Dagenais GR, Diaz R, Lakshmanan M, Pais P, et al. Dulaglutide and cardiovascular outcomes in type 2 diabetes (REWIND): a double-blind, randomised placebo-controlled trial. Lancet. 2019;394(10193):121–30.
Pfeffer MA, Claggett B, Diaz R, Dickstein K, Gerstein HC, Køber LV, et al. Lixisenatide in patients with type 2 diabetes and acute coronary syndrome. N Engl J Med. 2015;373(23):2247–57.
Andrikou E, Tsioufis C, Andrikou I, Leontsinis I, Tousoulis D, Papanas N. GLP-1 receptor agonists and cardiovascular outcome trials: An update. Hellenic J Cardiol. 2019;60(6):347–51.
Holman RR, Bethel MA, Mentz RJ, Thompson VP, Lokhnygina Y, Buse JB, et al. Effects of once-weekly exenatide on cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2017;377(13):1228–39.
Kristensen SL, Rørth R, Jhund PS, Docherty KF, Sattar N, Preiss D, et al. Cardiovascular, mortality, and kidney outcomes with GLP-1 receptor agonists in patients with type 2 diabetes: a systematic review and meta-analysis of cardiovascular outcome trials. Lancet Diabetes Endocrinol. 2019;7(10):776–85.
Saw M, Wong VW, Ho IV, Liew G. New anti-hyperglycaemic agents for type 2 diabetes and their effects on diabetic retinopathy. Eye (Lond). 2019;33(12):1842–51.
Cowart K. Oral semaglutide: first-in-class oral GLP-1 receptor agonist for the treatment of type 2 diabetes mellitus. Ann Pharmacother. 2020;54(5):478–85.
Amori RE, Lau J, Pittas AG. Efficacy and safety of incretin therapy in type 2 diabetes: systematic review and meta-analysis. JAMA. 2007;298(2):194–206.
Pratley RE, Rosenstock J, Pi-Sunyer FX, Banerji MA, Schweizer A, Couturier A, et al. Management of type 2 diabetes in treatment-naive elderly patients: benefits and risks of vildagliptin monotherapy. Diabetes Care. 2007;30(12):3017–22.
He YL, Sabo R, Campestrini J, Wang Y, Riviere GJ, Nielsen JC, et al. The effect of age, gender, and body mass index on the pharmacokinetics and pharmacodynamics of vildagliptin in healthy volunteers. Br J Clin Pharmacol. 2008;65(3):338–46.
Shankar RR, Xu L, Golm GT, O’Neill EA, Goldstein BJ, Kaufman KD, et al. A comparison of glycaemic effects of sitagliptin and sulfonylureas in elderly patients with type 2 diabetes mellitus. Int J Clin Pract. 2015;69(6):626–31.
Bae JH, Kim S, Park EG, Kim SG, Hahn S, Kim NH. Effects of dipeptidyl peptidase-4 inhibitors on renal outcomes in patients with type 2 diabetes: a systematic review and meta-analysis. Endocrinol Metab (Seoul). 2019;34(1):80–92.
Li L, Li S, Deng K, Liu J, Vandvik PO, Zhao P, et al. Dipeptidyl peptidase-4 inhibitors and risk of heart failure in type 2 diabetes: systematic review and meta-analysis of randomised and observational studies. BMJ. 2016;352:i610.
Mamza J, Marlin C, Wang C, Chokkalingam K, Idris I. DPP-4 inhibitor therapy and bone fractures in people with Type 2 diabetes—a systematic review and meta-analysis. Diabetes Res Clin Pract. 2016;116:288–98.
Makrilakis K. The role of DPP-4 inhibitors in the treatment algorithm of type 2 diabetes mellitus: when to select, what to expect. Int J Environ Res Public Health. 2019;16(15):2720.
Gilbert MP, Pratley RE. GLP-1 analogs and DPP-4 inhibitors in type 2 diabetes therapy: review of head-to-head clinical trials. Front Endocrinol (Lausanne). 2020;11:178.
Fioretto P, Zambon A, Rossato M, Busetto L, Vettor R. SGLT2 inhibitors and the diabetic kidney. Diabetes Care. 2016;39(Suppl 2):S165–71.
Vasilakou D, Karagiannis T, Athanasiadou E, Mainou M, Liakos A, Bekiari E, et al. Sodium-glucose cotransporter 2 inhibitors for type 2 diabetes: a systematic review and meta-analysis. Ann Intern Med. 2013;159(4):262–74.
Häring HU, Merker L, Seewaldt-Becker E, Weimer M, Meinicke T, Woerle HJ, et al. Empagliflozin as add-on to metformin plus sulfonylurea in patients with type 2 diabetes: a 24-week, randomized, double-blind, placebo-controlled trial. Diabetes Care. 2013;36(11):3396–404.
Ueda P, Svanström H, Melbye M, Eliasson B, Svensson AM, Franzén S, et al. Sodium glucose cotransporter 2 inhibitors and risk of serious adverse events: nationwide register based cohort study. BMJ. 2018;363:k4365.
Matthaei S, Bowering K, Rohwedder K, Grohl A, Parikh S. Dapagliflozin improves glycemic control and reduces body weight as add-on therapy to metformin plus sulfonylurea: a 24-week randomized, double-blind clinical trial. Diabetes Care. 2015;38(3):365–72.
Zannad F, Ferreira JP, Pocock SJ, Anker SD, Butler J, Filippatos G, et al. SGLT2 inhibitors in patients with heart failure with reduced ejection fraction: a meta-analysis of the EMPEROR-Reduced and DAPA-HF trials. Lancet. 2020;396(10254):819–29.
Ingelfinger JR, Rosen CJ. Clinical credence—SGLT2 inhibitors, diabetes, and chronic kidney disease. N Engl J Med. 2019;380(24):2371–3.
Jardiance FDA approval history. 2021. https://www.drugs.com/history/jardiance.html. Accessed 27 May 2021.
Farxiga FDA approval history. 2021. https://www.drugs.com/history/farxiga.html. Accessed 27 May 2021.
Fralick M, MacFadden DR. A hypothesis for why sodium glucose co-transporter 2 inhibitors have been found to cause genital infection, but not urinary tract infection. Diabetes Obes Metab. 2020;22(5):755–8.
Liu J, Li L, Li S, Jia P, Deng K, Chen W, et al. Effects of SGLT2 inhibitors on UTIs and genital infections in type 2 diabetes mellitus: a systematic review and meta-analysis. Sci Rep. 2017;7(1):2824.
Lega IC, Bronskill SE, Campitelli MA, Guan J, Stall NM, Lam K, et al. Sodium glucose cotransporter 2 inhibitors and risk of genital mycotic and urinary tract infection: a population-based study of older women and men with diabetes. Diabetes Obes Metab. 2019;21(11):2394–404.
Donnan JR, Grandy CA, Chibrikov E, Marra CA, Aubrey-Bassler K, Johnston K, et al. Comparative safety of the sodium glucose co-transporter 2 (SGLT2) inhibitors: a systematic review and meta-analysis. BMJ Open. 2019;9(1):e022577.
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(9):1687–93.
Blau JE, Tella SH, Taylor SI, Rother KI. Ketoacidosis associated with SGLT2 inhibitor treatment: Analysis of FAERS data. Diabetes Metab Res Rev. 2017;33:8.
Ferrannini E, Muscelli E, Frascerra S, Baldi S, Mari A, Heise T, et al. Metabolic response to sodium-glucose cotransporter 2 inhibition in type 2 diabetic patients. J Clin Invest. 2014;124(2):499–508.
Neal B, Perkovic V, Mahaffey KW, de Zeeuw D, Fulcher G, Erondu N, et al. Canagliflozin and cardiovascular and renal events in type 2 diabetes. N Engl J Med. 2017;377(7):644–57.
Inzucchi SE, Iliev H, Pfarr E, Zinman B. Empagliflozin and assessment of lower-limb amputations in the EMPA-REG OUTCOME trial. Diabetes Care. 2018;41(1):e4–5.
Potier L, Roussel R, Velho G, Saulnier PJ, Bumbu A, Matar O, et al. Lower limb events in individuals with type 2 diabetes: evidence for an increased risk associated with diuretic use. Diabetologia. 2019;62(6):939–47.
Li X, Li T, Cheng Y, Lu Y, Xue M, Xu L, et al. Effects of SGLT2 inhibitors on fractures and bone mineral density in type 2 diabetes: an updated meta-analysis. Diabetes Metab Res Rev. 2019;35(7):e3170.
Cheng L, Li YY, Hu W, Bai F, Hao HR, Yu WN, et al. Risk of bone fracture associated with sodium-glucose cotransporter-2 inhibitor treatment: a meta-analysis of randomized controlled trials. Diabetes Metab. 2019;45(5):436–45.
Milder TY, Stocker SL, Day RO, Greenfield JR. Potential safety issues with use of sodium-glucose cotransporter 2 inhibitors, particularly in people with type 2 diabetes and chronic kidney disease. Drug Saf. 2020;43(12):1211–21.
Esquivel MA, Lansang MC. Optimizing diabetes treatment in the presence of obesity. Cleve Clin J Med. 2017;84(7 Suppl 1):S22–9.
Singh-Franco D, Perez A, Harrington C. The effect of pramlintide acetate on glycemic control and weight in patients with type 2 diabetes mellitus and in obese patients without diabetes: a systematic review and meta-analysis. Diabetes Obes Metab. 2011;13(2):169–80.
Defronzo RA. Bromocriptine: a sympatholytic, d2-dopamine agonist for the treatment of type 2 diabetes. Diabetes Care. 2011;34(4):789–94.
Gaziano JM, Cincotta AH, O’Connor CM, Ezrokhi M, Rutty D, Ma ZJ, et al. Randomized clinical trial of quick-release bromocriptine among patients with type 2 diabetes on overall safety and cardiovascular outcomes. Diabetes Care. 2010;33(7):1503–8.
Nwose OM, Jones MR. Atypical mechanism of glucose modulation by colesevelam in patients with type 2 diabetes. Clin Med Insights Endocrinol Diabetes. 2013;6:75–9.
Ooi CP, Loke SC. Colesevelam for type 2 diabetes mellitus. Cochrane Database Syst Rev. 2012;12(12):CD009361.
Saudek CD, Brick JC. The clinical use of hemoglobin A1c. J Diabetes Sci Technol. 2009;3(4):629–34.
Radin MS. Pitfalls in hemoglobin A1c measurement: when results may be misleading. J Gen Intern Med. 2014;29(2):388–94.
Halimi S. Acute consequences of hypoglycaemia in diabetic patients. Diabetes Metab. 2010;36(Suppl 3):S75-83.
Malanda UL, Welschen LM, Riphagen II, Dekker JM, Nijpels G, Bot SD. Self-monitoring of blood glucose in patients with type 2 diabetes mellitus who are not using insulin. Cochrane Database Syst Rev. 2012;1:CD005060.
Newton CA, Adeel S, Sadeghi-Yarandi S, Powell W, Migdal A, Smiley D, et al. Prevalence, quality of care, and complications in long term care residents with diabetes: a multicenter observational study. J Am Med Dir Assoc. 2013;14(11):842–6.
Resnick HE, Heineman J, Stone R, Shorr RI. Diabetes in US nursing homes, 2004. Diabetes Care. 2008;31(2):287–8.
Dybicz SB, Thompson S, Molotsky S, Stuart B. Prevalence of diabetes and the burden of comorbid conditions among elderly nursing home residents. Am J Geriatr Pharmacother. 2011;9(4):212–23.
Neuwahl SJ, Honeycutt AA, Poehler DC, Shrestha SS, Zhang P, Hoerger TJ. Diabetes-attributable nursing home costs for each US state. Diabetes Care. 2018;41(7):1455–61.
Lipska KJ, Ross JS, Wang Y, Inzucchi SE, Minges K, Karter AJ, et al. National trends in US hospital admissions for hyperglycemia and hypoglycemia among Medicare beneficiaries, 1999 to 2011. JAMA Intern Med. 2014;174(7):1116–24.
Thomson FJ, Masson EA, Leeming JT, Boulton AJ. Lack of knowledge of symptoms of hypoglycaemia by elderly diabetic patients. Age Ageing. 1991;20(6):404–6.
Dorner B, Friedrich EK, Posthauer ME. Position of the American Dietetic Association: individualized nutrition approaches for older adults in health care communities. J Am Diet Assoc. 2010;110(10):1549–53.
Munshi MN, Florez H, Huang ES, Kalyani RR, Mupanomunda M, Pandya N, et al. Management of diabetes in long-term care and skilled nursing facilities: a position statement of the american diabetes association. Diabetes Care. 2016;39(2):308–18.
Elia M, Ceriello A, Laube H, Sinclair AJ, Engfer M, Stratton RJ. Enteral nutritional support and use of diabetes-specific formulas for patients with diabetes: a systematic review and meta-analysis. Diabetes Care. 2005;28(9):2267–79.
Pandya N, Thompson S, Sambamoorthi U. The prevalence and persistence of sliding scale insulin use among newly admitted elderly nursing home residents with diabetes mellitus. J Am Med Dir Assoc. 2008;9(9):663–9.
Umpierrez GE, Palacio A, Smiley D. Sliding scale insulin use: myth or insanity? Am J Med. 2007;120(7):563–7.
Pauly L, Stehle P, Volkert D. Nutritional situation of elderly nursing home residents. Z Gerontol Geriatr. 2007;40(1):3–12.
Mooradian AD, Chehade JM. Diabetes mellitus in older adults. Am J Ther. 2012;19(2):145–59.
Launer LJ, Miller ME, Williamson JD, Lazar RM, Gerstein HC, Murray AM, et al. Effects of intensive glucose lowering on brain structure and function in people with type 2 diabetes (ACCORD MIND): a randomised open-label substudy. Lancet Neurol. 2011;10(11):969–77.
Gerstein HC, Miller ME, Byington RP, Goff DC Jr, Bigger JT, Buse JB, et al. Effects of intensive glucose lowering in type 2 diabetes. N Engl J Med. 2008;358(24):2545–59.
Jacobson AM, Musen G, Ryan CM, Silvers N, Cleary P, Waberski B, et al. Long-term effect of diabetes and its treatment on cognitive function. N Engl J Med. 2007;356(18):1842–52.
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Gandhi, G.Y., Mooradian, A.D. Management of Hyperglycemia in Older Adults with Type 2 Diabetes. Drugs Aging 39, 39–58 (2022). https://doi.org/10.1007/s40266-021-00910-1
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DOI: https://doi.org/10.1007/s40266-021-00910-1