Hypoglycemia in Older Adults: Time Trends and Treatment Differences in Patients Aged ≥75 Years With Type 2 Diabetes



      Hypoglycemia is a potentially life-threatening drug event under antidiabetic treatment. The aim of the study was to examine time trends in severe hypoglycemia in older adults with type 2 diabetes mellitus (T2DM) and antidiabetic treatment.


      Multicenter prospective diabetes patient follow-up registry (DPV).

      Setting and Participants

      Patients aged ≥75 years with T2DM and documented treatment between 2005 and 2019.


      Outcomes of interest were rates of severe hypoglycemia, diabetes therapy, body mass index, HbA1c, and estimated glomerular filtration rate. Time trends of outcomes were analyzed in the whole cohort and compared between age groups (75–<80, 80–<85, ≥85 years).


      A total of 136,931 patients from 188 diabetes centers were included. The adjusted HbA1c decreased from 7.3% (95% confidence interval 7.3–7.4) in 2005 to 7.2% (7.2–7.2) in 2019 (P < .001), with no significant difference between age groups (P = .47). Rates of severe hypoglycemia decreased from 6.7 (6.0–7.4) to 4.1 of 100 person-years (3.7–4.5) (P < .001) in the entire population. Patients aged ≥85 years had constantly lower HbA1c levels compared with younger groups (P < .001). Although severe hypoglycemia decreased the most in the ≥85 age group (P < .001), severe hypoglycemia remained consistently higher in this group compared with the 75 to <80 years group (P < .001).

      Conclusions and Implications

      During the analyzed time, the risk for severe hypoglycemia decreased. Although drugs with intrinsic risk for hypoglycemia were used less frequently, antidiabetic treatment in older adults should be further improved to continue reducing severe hypoglycemia in this age group, potentially accepting less strict metabolic control and age-specific target ranges.


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        • American Diabetes Association
        12. Older adults: Standards of medical care in diabetes—2020.
        Diabetes Care. 2020; 43: S152-S162
        • Klotz U.
        Pharmacokinetics and drug metabolism in the elderly.
        Drug Metab Rev. 2009; 41: 67-76
        • Rawshani A.
        • Rawshani A.
        • Franzén S.
        • et al.
        Risk factors, mortality, and cardiovascular outcomes in patients with type 2 diabetes.
        N Engl J Med. 2018; 379: 633-644
        • Lipska K.J.
        • Krumholz H.
        • Soones T.
        • et al.
        Polypharmacy in the aging patient: A review of glycemic control in older adults with type 2 diabetes.
        JAMA. 2016; 315: 1034-1045
        • Prinz N.
        • Stingl J.
        • Dapp A.
        • et al.
        High rate of hypoglycemia in 6770 type 2 diabetes patients with comorbid dementia: A multicenter cohort study on 215,932 patients from the German/Austrian diabetes registry.
        Diabetes Res Clin Pract. 2016; 112: 73-81
        • Mattishent K.
        • Loke Y.K.
        Bi-directional interaction between hypoglycaemia and cognitive impairment in elderly patients treated with glucose-lowering agents: A systematic review and meta-analysis.
        Diabetes Obes Metab. 2016; 18: 135-141
        • Yaffe K.
        • Falvey C.M.
        • Hamilton N.
        • et al.
        Association between hypoglycemia and dementia in a biracial cohort of older adults with diabetes mellitus.
        JAMA Intern Med. 2013; 173: 1300-1306
        • Cosentino F.
        • Grant P.J.
        • Aboyans V.
        • et al.
        2019 ESC guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD: The task force for diabetes, pre-diabetes, and cardiovascular diseases of the European Society of cardiology (ESC) and the European association for the study of diabetes (EASD).
        Eur Heart J. 2020; 41: 255-323
        • National Institute for Health and Care Excellence
        NICE guideline: Type 2 diabetes in adults: management. Updated December 2020.
        (Available at:)
        • Deutsche Diabetes Gesellschaft
        S2k-Leitlinie Diagnostik, Therapie und Verlaufskontrolle des Diabetes mellitus im Alter.
        (Available at:)
        • Sinclair A.
        • Morley J.E.
        • Rodriguez-Mañas L.
        • et al.
        Diabetes mellitus in older people: Position statement on behalf of the International Association of Gerontology and Geriatrics (IAGG), the European Diabetes Working Party for Older People (EDWPOP), and the International Task Force of Experts in Diabetes.
        J Am Med Dir Assoc. 2012; 13: 497-502
        • Budnitz D.S.
        • Lovegrove M.C.
        • Shehab N.
        • et al.
        Emergency hospitalizations for adverse drug events in older Americans.
        N Engl J Med. 2011; 365: 2002-2012
        • Just K.S.
        • Dormann H.
        • Bohme M.
        • et al.
        Personalising drug safety-results from the multi-centre prospective observational study on Adverse Drug Reactions in Emergency Departments (ADRED).
        Eur J Clin Pharmacol. 2020; 76: 439-448
        • Konrat C.
        • Boutron I.
        • Trinquart L.
        • et al.
        Underrepresentation of elderly people in randomised controlled trials. The example of trials of 4 widely prescribed drugs.
        PLoS One. 2012; 7: e33559
        • Cerreta F.
        • Eichler H.G.
        • Rasi G.
        Drug policy for an aging population--the European Medicines Agency's geriatric medicines strategy.
        N Engl J Med. 2012; 367: 1972-1974
        • Oeppen J.
        • Vaupel J.W.
        Broken limits to life expectancy.
        Science. 2002; 296: 1029-1031
        • Robine J.M.
        • Cubaynes S.
        Worldwide demography of centenarians.
        Mech Ageing Dev. 2017; 165: 59-67
        • Craig M.E.
        • Prinz N.
        • Boyle C.T.
        • et al.
        Prevalence of celiac disease in 52,721 youth with type 1 diabetes: international comparison across three continents.
        Diabetes Care. 2017; 40: 1034-1040
        • Schwandt A.
        • Denkinger M.
        • Fasching P.
        • et al.
        Comparison of MDRD, CKD-EPI, and Cockcroft-Gault equation in relation to measured glomerular filtration rate among a large cohort with diabetes.
        J Diabetes Complications. 2017; 31: 1376-1383
        • Sinclair A.
        • Dunning T.
        • Rodriguez-Mañas L.
        Diabetes in older people: new insights and remaining challenges.
        Lancet Diabetes Endocrinol. 2015; 3: 275-285
        • Abdelhafiz A.H.
        • Rodríguez-Mañas L.
        • Morley J.E.
        • et al.
        Hypoglycemia in older people - a less well recognized risk factor for frailty.
        Aging Dis. 2015; 6: 156-167
        • Schwartz A.V.
        • Hillier T.A.
        • Sellmeyer D.E.
        • et al.
        Older women with diabetes have a higher risk of falls: A prospective study.
        Diabetes Care. 2002; 25: 1749-1754
        • Lee A.K.
        • Juraschek S.P.
        • Windham B.G.
        • et al.
        Severe hypoglycemia and risk of falls in type 2 diabetes: The Atherosclerosis Risk in Communities (ARIC) Study.
        Diabetes Care. 2020; 43: 2060-2065
        • Strain W.D.
        • Hope S.V.
        • Green A.
        • et al.
        Type 2 diabetes mellitus in older people: A brief statement of key principles of modern day management including the assessment of frailty. A national collaborative stakeholder initiative.
        Diabet Med. 2018; 35: 838-845
        • Lipska K.J.
        • Yao X.
        • Herrin J.
        • et al.
        Trends in drug utilization, glycemic control, and rates of severe hypoglycemia, 2006–2013.
        Diabetes Care. 2017; 40: 468-475
        • Scheuing N.
        • Best F.
        • Dapp A.
        • et al.
        Multicentre analysis of 178,992 type 2 diabetes patients revealed better metabolic control despite higher rates of hypertension, stroke, dementia and repeated inpatient care in patients with comorbid Parkinson's disease.
        Parkinsonism Relat Disord. 2013; 19: 687-692
        • Pani L.N.
        • Korenda L.
        • Meigs J.B.
        • et al.
        Effect of aging on A1C levels in individuals without diabetes: evidence from the Framingham Offspring Study and the National Health and Nutrition Examination Survey 2001–2004.
        Diabetes Care. 2008; 31: 1991-1996
        • Ahadi S.
        • Zhou W.
        • Schüssler-Fiorenza Rose S.M.
        • et al.
        Personal aging markers and ageotypes revealed by deep longitudinal profiling.
        Nat Med. 2020; 26: 83-90
        • Roth J.
        • Müller N.
        • Lehmann T.
        • et al.
        HbA1c and age in non-diabetic subjects: An Ignored association?.
        Exp Clin Endocrinol Diabetes. 2016; 124: 637-642
        • Davey A.
        • Lele U.
        • Elias M.F.
        • et al.
        Diabetes mellitus in centenarians.
        J Am Geriatr Soc. 2012; 60: 468-473
        • Kilpatrick E.S.
        • Bloomgarden Z.T.
        • Zimmet P.Z.
        Is haemoglobin A1c a step forward for diagnosing diabetes?.
        BMJ. 2009; 339: b4432
        • Hare M.J.
        • Shaw J.E.
        • Zimmet P.Z.
        Current controversies in the use of haemoglobin A1c.
        J Intern Med. 2012; 271: 227-236
        • Sacks D.B.
        Measurement of hemoglobin A(1c): A new twist on the path to harmony.
        Diabetes Care. 2012; 35: 2674-2680
        • Le P.
        • Chaitoff A.
        • Misra-Hebert A.D.
        • et al.
        Use of antihyperglycemic medications in U.S. adults: An analysis of the National Health and Nutrition Examination Survey.
        Diabetes Care. 2020; 43: 1227-1233
        • Strain W.D.
        • Lukashevich V.
        • Kothny W.
        • et al.
        Individualised treatment targets for elderly patients with type 2 diabetes using vildagliptin add-on or lone therapy (INTERVAL): A 24 week, randomised, double-blind, placebo-controlled study.
        Lancet. 2013; 382: 409-416
        • Ling J.
        • Cheng P.
        • Ge L.
        • et al.
        The efficacy and safety of dipeptidyl peptidase-4 inhibitors for type 2 diabetes: A Bayesian network meta-analysis of 58 randomized controlled trials.
        Acta Diabetol. 2019; 56: 249-272
        • Geller A.I.
        • Shehab N.
        • Lovegrove M.C.
        • et al.
        National estimates of insulin-related hypoglycemia and errors leading to emergency department visits and hospitalizations.
        JAMA Intern Med. 2014; 174: 678-686
        • Abbatecola A.M.
        • Bo M.
        • Barbagallo M.
        • et al.
        Severe hypoglycemia is associated with antidiabetic oral treatment compared with insulin analogs in nursing home patients with type 2 diabetes and dementia: Results from the DIMORA study.
        J Am Med Dir Assoc. 2015; 16: 349.e7-349.e12
        • Hirsch I.B.
        • Gaudiani L.M.
        Using insulin to treat poorly controlled type 2 diabetes in 2020.
        JAMA. 2020; 323: 2419-2420