How safe is the use of thiazolidinediones in clinical practice?
Abstract
BACKGROUND: Thiazolidinediones (TZDs) are widely used antidiabetic drugs with proven efficacy regarding mainly surrogate markers of diabetes management. However, efficacy on surrogate markers may not always translate into benefits in clinical outcomes. Thiazolidinediones are usually well tolerated; however, their use may be associated with several adverse effects. The first TZD, troglitazone, was withdrawn from the market owing to serious hepatotoxicity. However, this does not seem to be the case with newer TZDs. OBJECTIVE: The aim of the present review is to discuss the safety profile of this drug class. METHODS: We searched PubMed up to July 2008 using relevant keywords. CONCLUSIONS: Common side effects associated with TZDs include edema, weight gain, macular edema and heart failure. Moreover, they may cause hypoglycemia when combined with other antidiabetic drugs as well as decrease hematocrit and hemoglobin levels. Increased bone fracture risk is another TZD-related side effect. Thiazolidinediones tend to increase serum low density lipoprotein cholesterol levels, with rosiglitazone having a more pronounced effect compared with pioglitazone. Moreover, rosiglitazone increases low density lipoprotein particle concentration in contrast to pioglitazone where a decrease is observed. Rosiglitazone has been associated with an increase in myocardial infarction incidence. On the other hand, pioglitazone may reduce cardiovascular events. Overall, TZDs are valuable drugs for diabetes management but physicians should keep in mind that they are associated with several adverse events, the most prominent of which is heart failure.
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Side effects reported for pioglitazone include weight gain and risk of heart failure and macular edema.
“Side effects reported include weight gain and risk of heart failure and macular edema (190).”
From Evaluation and Treatment of Hypertriglyceridemia: An Endocrine Society Clinical Practice Guideline (2012) · cites this paper as [190]
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Dyslipidaemia, Hypercoagulability and the Metabolic Syndrome
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Self-citationEffects of Thiazolidinediones on Stroke Recovery: A Case-Matched Controlled Study
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Rosiglitazone-Induced Granulomatous Hepatitis
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Toxic effect of troglitazone on cultured rat hepatocytes
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Pioglitazone Stimulates Apolipoprotein A-I Production Without Affecting HDL Removal in HepG2 Cells
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POTENTIAL INTERACTION OF TROGLITAZONE AND CYCLOSPORINE
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Severe Hypo-α-Lipoproteinemia During Treatment With Rosiglitazone
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Angioneurotic Edema as a Side Effect of Pioglitazone
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Late-Onset Rosiglitazone-Associated Acute Liver Failure in a Patient with Hodgkin's Lymphoma
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Pharmacological treatment of non-alcoholic steatohepatitis: The current evidence
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Self-citationUnilateral Edema Due to a Thiazolidinedione
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Fracture Risk In Postmenopausal Women
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The cellular and signaling networks linking the immune system and metabolism in disease
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Evaluation and Treatment of Hypertriglyceridemia: An Endocrine Society Clinical Practice Guideline
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Immune System: An Emerging Player in Mediating Effects of Endocrine Disruptors on Metabolic Health
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Role of diet and exercise in aging, Alzheimer’s disease, and other chronic diseases
Khemka, S., Reddy, A., Garcia, R. I., Jacobs, M., Reddy, R. P., Roghani, A. K., Pattoor, V., Basu, T., Sehar, U., & Reddy, P. H. (2023) · Ageing Research Reviews · doi:10.1016/j.arr.2023.102091 · Cited by 88 · see citing works
Liu, Y., Vu, V., & Sweeney, G. (2019) · Frontiers in Endocrinology · doi:10.3389/fendo.2019.00842 · Cited by 69 · see citing works
- Authors
- Rizos, C., Elisaf, M., Mikhailidis, D., & Liberopoulos, E.
- Affiliations
- University of Ioannina (GR)
- ORCID
- Elisaf, Moses
- Venue
- Expert Opinion on Drug Safety
- Publisher
- Informa UK Limited
- Published
- 2008-11-25
- Volume
- 8
- Issue
- 1
- Pages
- 15-32
- ISSN
- 1474-0338 (ISSN-L)
- 1744-764X
- OpenAlex
- W1997490166
- Cited by
- 161
- References
- 158
- Citations by year
- 2026: 2 · 2025: 8 · 2024: 8 · 2023: 12 · 2022: 7 · 2021: 11 · 2020: 7 · 2019: 12 · 2018: 7 · 2017: 10 · 2016: 11 · 2015: 7 · 2014: 7 · 2013: 8 · 2012: 10
- FWCI
- 1.57
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Expert Opinion on Drug Safety (publishedVersion)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
- Health Sciences › Medicine › Pharmacology › Pharmacology and Obesity Treatment
- Keywords
- thiazolidinediones, drug safety, adverse drug reactions, rosiglitazone, pioglitazone, troglitazone, heart failure, hypoglycemia, bone fracture risk, LDL cholesterol, myocardial infarction, macular edema, edema, diabetes management
- MeSH terms
- Cardiovascular Diseases, Diabetes Mellitus, Type 2, Drug Interactions, Humans, Hypoglycemic Agents, Macular Edema, Weight Gain, Thiazolidinediones, Fractures, Bone
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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