Online first
Review article
Published online: 2024-07-11

open access

Page views 42
Article views/downloads 20
Get Citation

Connect on Social Media

Connect on Social Media

Randomized Controlled Trials Dedicated to Older Patients with Type 2 Diabetes: A Systematic Review

Maksymilian Sito1, Danuta Kłosowska2, Leszek Pączek2, Jan Borysowski2


Objective: Older adults with type 2 diabetes (T2D) comprise a very diverse population regarding their age, comorbidities, and frailty status, and their treatment goals may be different from those typical of younger patients. The objective of this study was to assess participants’ characteristics and the primary endpoints of randomized controlled trials (RCTs) dedicated to older adults with T2D. Materials and methods: This study was a systematic review of RCTs enrolling solely patients with T2D aged 60 years or older published from 1994 through 2023. Eligible trials were searched for in PubMed, Embase, and Cochrane Central. Results: The review included 35 RCTs (9068 participants). The weighted mean age of RCT participants was 71.4 years (co-primary outcome). The proportion of patients aged 75 years or older was reported in 11 (31%) RCTs; it was 27%. Proportion of patients with frailty was reported in 2 (6%) trials (co-primary outcome). The proportion of patients with different burden of comorbidities was provided in one (3%) RCT (co-primary outcome). The primary endpoints mostly (n = 25; 71%) involved HbA1c. A composite primary endpoint (reduction of HbA1c without significant hypoglycemia) was used in 2 (6%) trials. The results for the primary endpoints were generally positive. Conclusions: Most of the analyzed RCTs did not report the key participants characteristics. The primary endpoints did not involve outcome measures particularly relevant to older patients. Modifications of the design and reporting of RCTs should be considered to translate their results into optimal clinical care of older adults with T2D.

Article available in PDF format

View PDF Download PDF file


  1. Sinclair A, Dunning T, Rodriguez-Mañas L. Diabetes in older people: new insights and remaining challenges. Lancet Diabetes Endocrinol. 2015; 3(4): 275–285.
  2. Menke A, Casagrande S, Geiss L, et al. Prevalence of and Trends in Diabetes Among Adults in the United States, 1988-2012. JAMA. 2015; 314(10): 1021–1029.
  3. Li Y, Teng Di, Shi X, et al. Prevalence of diabetes recorded in mainland China using 2018 diagnostic criteria from the American Diabetes Association: national cross sectional study. BMJ. 2020; 369: m997.
  4. Milanesi A, Weinreb JE. Diabetes in the Elderly. In: Feingold KR, Anawalt B, Blackman MR. ed. Endotext [Internet]., Inc., South Darmouth (MA) 2020.
  5. Bianchi L, Zuliani G, Volpato S. Physical disability in the elderly with diabetes: epidemiology and mechanisms. Curr Diab Rep. 2013; 13(6): 824–830.
  6. Sinclair A, Abdelhafiz A. Cognitive Dysfunction in Older Adults with Type 2 Diabetes: Links, Risks, and Clinical Implications. Clin Geriatr Med. 2020; 36(3): 407–417.
  7. Laiteerapong N, Karter AJ, Liu JY, et al. Correlates of quality of life in older adults with diabetes: the diabetes & aging study. Diabetes Care. 2011; 34(8): 1749–1753.
  8. Bellary S, Kyrou I, Brown JE, et al. Type 2 diabetes mellitus in older adults: clinical considerations and management. Nat Rev Endocrinol. 2021; 17(9): 534–548.
  9. Sinclair AJ, Abdelhafiz AH. Multimorbidity, Frailty and Diabetes in Older People-Identifying Interrelationships and Outcomes. J Pers Med. 2022; 12(11).
  10. Huang ES. Management of diabetes mellitus in older people with comorbidities. BMJ. 2016; 353: i2200.
  11. Caughey GE, Roughead EE, Vitry AI, et al. Comorbidity in the elderly with diabetes: Identification of areas of potential treatment conflicts. Diabetes Res Clin Pract. 2010; 87(3): 385–393.
  12. Strain WD, Down Su, Brown P, et al. Diabetes and Frailty: An Expert Consensus Statement on the Management of Older Adults with Type 2 Diabetes. Diabetes Ther. 2021; 12(5): 1227–1247.
  13. Cruz-Jentoft AJ, Carpena-Ruiz M, Montero-Errasquín B, et al. Exclusion of older adults from ongoing clinical trials about type 2 diabetes mellitus. J Am Geriatr Soc. 2013; 61(5): 734–738.
  14. Lakey WC, Barnard K, Batch BC, et al. Are current clinical trials in diabetes addressing important issues in diabetes care? Diabetologia. 2013; 56(6): 1226–1235.
  15. Sinclair AJ, Heller SR, Pratley RE, et al. Evaluating glucose-lowering treatment in older people with diabetes: Lessons from the IMPERIUM trial. Diabetes Obes Metab. 2020; 22(8): 1231–1242.
  16. Strait A, Castillo F, Choden S, et al. Demographic Characteristics of Participants in Rheumatoid Arthritis Randomized Clinical Trials: A Systematic Review. JAMA Netw Open. 2019; 2(11): e1914745.
  17. Tahhan AS, Vaduganathan M, Greene SJ, et al. Enrollment of Older Patients, Women, and Racial/Ethnic Minority Groups in Contemporary Acute Coronary Syndrome Clinical Trials: A Systematic Review. JAMA Cardiol. 2020; 5(6): 714–722.
  18. Heller SR, Pratley RE, Sinclair A, et al. Glycaemic outcomes of an Individualized treatMent aPproach for oldER vulnerable patIents: A randomized, controlled stUdy in type 2 diabetes Mellitus (IMPERIUM). Diabetes Obes Metab. 2018; 20(1): 148–156.
  19. Schernthaner G, Durán-Garcia S, Hanefeld M, et al. Efficacy and tolerability of saxagliptin compared with glimepiride in elderly patients with type 2 diabetes: a randomized, controlled study (GENERATION). Diabetes Obes Metab. 2015; 17(7): 630–638.
  20. Herz M, Sun B, Milicevic Z, et al. Comparative efficacy of preprandial or postprandial Humalog Mix75/25 versus glyburide in patients 60 to 80 years of age with type 2 diabetes mellitus. Clin Ther. 2002; 24(1): 73–86.
  21. Strain WD, 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(9890): 409–416.
  22. Yabe D, Shiki K, Homma G, et al. EMPA-ELDERLY Investigators. Efficacy and safety of the sodium-glucose co-transporter-2 inhibitor empagliflozin in elderly Japanese adults (≥65 years) with type 2 diabetes: A randomized, double-blind, placebo-controlled, 52-week clinical trial (EMPA-ELDERLY). Diabetes Obes Metab. 2023; 25(12): 3538–3548.
  23. Nagao M, Sasaki J, Sugihara H, et al. STREAM Study Investigators. Efficacy and safety of sitagliptin treatment in older adults with moderately controlled type 2 diabetes: the STREAM study. Sci Rep. 2023; 13(1): 134.
  24. Thomas MC, Cooper ME, Zimmet P. Changing epidemiology of type 2 diabetes mellitus and associated chronic kidney disease. Nat Rev Nephrol. 2016; 12(2): 73–81.
  25. Thomas MC, Brownlee M, Susztak K, et al. Diabetic kidney disease. Nat Rev Dis Primers. 2015; 1: 15018.
  26. Game F. Novel hypoglycaemic agents: considerations in patients with chronic kidney disease. Nephron Clin Pract. 2014; 126(1): 14–18.
  27. Lau SW, Huang Y, Hsieh J, et al. Participation of Older Adults in Clinical Trials for New Drug Applications and Biologics License Applications From 2010 Through 2019. JAMA Netw Open. 2022; 5(10): e2236149.
  28. Sircar M, Bhatia A, Munshi M. Review of Hypoglycemia in the Older Adult: Clinical Implications and Management. Can J Diabetes. 2016; 40(1): 66–72.