Research Paper Volume 15, Issue 7 pp 2721—2733

Pioglitazone reduces cardiovascular events and dementia but increases bone fracture in elderly patients with type 2 diabetes mellitus: a national cohort study

Chieh-Li Yen1, , Chao-Yi Wu2,3, , Chung-Ying Tsai1, , Cheng-Chia Lee1, , Yi-Jung Li1, , Wei-Sheng Peng4, , Jia-Rou Liu4, , Yuan-Chang Liu5, , Chang-Chyi Jenq1, , Huang-Yu Yang1,6, *, , Lai-Chu See4, *, ,

  • 1 Department of Nephrology, Kidney Research Institute, Chang Gung Memorial Hospital at Linkou, College of Medicine, Chang Gung University, Taoyuan City, Taiwan
  • 2 Department of Internal Medicine, Division of Rheumatology, Allergy and Immunology, Chang Gung Memorial Hospital at Linkou, Taoyuan City, Taiwan
  • 3 Department of Pediatrics, Division of Allergy, Asthma and Rheumatology, Chang Gung Memorial Hospital at Linkou, College of Medicine, Chang Gung University, Taoyuan City, Taiwan
  • 4 Department of Public Health, College of Medicine, Biostatistics Core Laboratory, Molecular Medicine Research Center, Chang Gung University, Taoyuan City, Taiwan
  • 5 Department of Medical Imaging and intervention, Chang Gung Memorial Hospital at Linkou, Taoyuan City, Taiwan
  • 6 Department of Health Policy and Management, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD 21205, USA
* Equal contribution

Received: June 14, 2022       Accepted: March 15, 2023       Published: April 7, 2023
How to Cite

Copyright: © 2023 Yen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


The prevalence of type 2 diabetes (T2DM) in elderly people has expanded rapidly. Considering cognitive impairment and being prone to hypoglycemia of the elder, the pros and cons of oral hypoglycemic agents (OHA) should be reassessed in this population. Pioglitazone might be appropriate for elderly DM patients because of its insulin-sensitizing effect and low risk of hypoglycemia.

By using Taiwan’s National Health Insurance Research Database, 191,937 types 2 diabetes patients aged ≥65 years under treatment between 2005 and 2013 were identified and further divided into two groups according to whether they received pioglitazone (pioglitazone group) or other OHAs (non-pioglitazone group) in the 3 months preceding their first outpatient visit date after 65 years of age, with a diagnosis of T2DM. Propensity score stabilization weight (PSSW) was used to balance the baseline characteristics. In results, the pioglitazone group (n = 17,388) exhibited a lower rate (per person-years) of major advanced cardiovascular events MACCE (2.76% vs. 3.03%, hazard ratio [HR]: 0.91, 95% confidence interval [CI]: 0.87–0.95), new- diagnosis dementia (1.32% vs. 1.46%, HR: 0.91, 95% CI: 0.84–0.98) but a higher rate of new-diagnosis bone fractures (5.37% vs. 4.47%, HR: 1.24, 95% CI: 1.19–1.28) than the non-pioglitazone group (n = 174,549). In conclusion, using pioglitazone may reduce the risks of MACCE and dementia but increases the probability of bone fractures in the elderly DM population.


T2DM: type 2 diabetes mellitus; CV: cardiovascular; OHA: oral hypoglycemic agents; TZD: thiazolidinedione; PPAR-γ: peroxisome proliferator-activated receptor gamma; CKD: chronic kidney disease; NHIRD: National Health Insurance Research Database; CCI: Charlson Comorbidity Index; MACCE: major adverse cardiac and cerebrovascular events; ASMD: absolute standardized mean difference; SGLT2: sodium-glucose cotransporter 2; GLP-1: glucagon-like peptide-1.