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Effects of pioglitazone on lipid and lipoprotein metabolism.
Abstract
Type 2 diabetes is associated with an increased risk of cardiovascular disease (CVD). A major contributing factor to this risk is the abnormal lipid profile known as dyslipidaemia, which is characterized by low HDL cholesterol (HDL-C), raised triglycerides (TGs) and a predominance of small, dense LDL cholesterol (LDL-C) particles. Statins are now widely used first-line in patients with type 2 diabetes due to their proven efficacy in reducing LDL-C and cardiovascular risk. However, despite the use of statins, the absolute risk of CVD in patients remains elevated, highlighting the need to target all aspects of the diabetic lipid profile such as raised TGs or low HDL-C levels. Insulin resistance is thought to be central in the pathogenesis of diabetic dyslipidaemia; therefore, improving insulin sensitivity with a thiazolidinedione offers an attractive treatment option. Indeed, pioglitazone, a member of the peroxisome proliferator-activated receptor-gamma family, has been shown in clinical trials to improve both blood glucose levels and the lipid profile when used either as monotherapy or in combination with other oral antidiabetic agents. In the monotherapy setting, pioglitazone has been associated with greater decreases in TGs and increases in HDL-C when compared with glibenclamide or metformin. Studies investigating the effects of pioglitazone add-on therapy to either metformin or sulphonylurea treatments have shown sustained improvements in serum levels of TGs and HDL-C and favourable effects on LDL-C particle size. In comparison with rosiglitazone, pioglitazone has different and potentially favourable effects on plasma lipids. The recent PROspective pioglitAzone Clinical Trial In macroVascular Events study has given weight to the hypothesis that the beneficial metabolic effects of pioglitazone may be associated with reductions in cardiovascular risk in patients with type 2 diabetes.
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Pioglitazone has a mild triglyceride-lowering effect, whereas rosiglitazone does not lower triglycerides.
“Pioglitazone, a peroxisome proliferator-activated receptor-␥ agonist, has a mild triglyceride-lowering effect, whereas rosiglitazone does not lower triglycerides (188,189).”
From Evaluation and Treatment of Hypertriglyceridemia: An Endocrine Society Clinical Practice Guideline (2012) · cites this paper as [189]
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MethodResultManagement of Cardiovascular Risk in the Non‑alcoholic Fatty Liver Disease Setting
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“This result is consistent with previous reports [16,22] and is thought to be mediated by the increased expression of apolipoprotein A1 by thiazolidinedione [23].”
Tan, A., Cao, Y., Xia, N., Mo, Z., & Gao, F. (2010) · European Journal of Internal Medicine · doi:10.1016/j.ejim.2010.03.018 · Cited by 7
“At the same time, a small but significant increase in LDL-c was also observed in this metaanalysis, which was likely to represent an increase in LDL particle size [29].”
BackgroundRosiglitazone Causes Endothelial Dysfunction in Humans
Perampaladas, K., Gori, T., & Parker, J. D. (2011) · Journal of Cardiovascular Pharmacology and Therapeutics · doi:10.1177/1074248411425490 · Cited by 7
“Furthermore, thiazolidinediones also have favorable effects on free fatty acid and cholesterol profiles in patients with metabolic syndrome or frank diabetes which can also lead to a decrease in free radical bioavailability.(27,28) Therefore, the beneficial effects of thiazolidinediones on endothelial function may be…”
BackgroundEvolution of Glucose-Lowering Drugs for Type 2 Diabetes
Krentz, A. J. (2018) · Elsevier eBooks · doi:10.1016/b978-0-12-812019-4.00033-7 · Cited by 7
Evaluation of Biochemical Toxicity and Antioxidant Properties of Pioglitazone on Albino Wistar Rats
Ogunlana, O. O., Ogunlana, O. E., Ugochukwu, S. K., & Ashano, E. (2017) · Journal of Medical Sciences(Faisalabad) · doi:10.3923/jms.2017.10.16 · Cited by 6
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Unintended positive and negative effects of drugs on lipoproteins
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“TZD is a member of the peroxisome proliferator-activated receptor-γ agonists family (PPAR γ ), which has been used in clinical trials, either alone or in combination with oral antidiabetic medication to treat patients with T2DM (14).”
InfluentialWithdrawal of pioglitazone in patients with type 2 diabetes mellitus
Iwase, M., Asano, T., Sasaki, N., Yoshizumi, H., Hiramatsu, S., Sakai, Y., Ogo, A., & Iida, M. (2010) · Journal of Clinical Pharmacy and Therapeutics · doi:10.1111/j.1365-2710.2009.01109.x · Cited by 4
“In addition, pioglitazone has beneficial effects on non-alcoholic fatty liver disease (14), lipoprotein profile (15), systemic inflammatory, coagulation markers and endothelial cell function (16, 17).”
BackgroundEffects of Pioglitazone On Lipoprotein(a): A Meta-analysis
Jamialahmadi, T., Mirhadi, E., Reiner, Ž., Abass, K. S., Almahmeed, W. A., Virani, S. S., & Sahebkar, A. (2025) · Current Atherosclerosis Reports · doi:10.1007/s11883-025-01346-3 · Cited by 3
“Notably, pioglitazone has been reported to have a beneficial effect on the lipid profile [23].”
Pharmacologic Treatment of Dyslipidemia in Diabetes: A Case for Therapies in Addition to Statins
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Comparative urinary metabolomics reveals unique and shared pathways in COVID-19 and liver diseases
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“Citric acid emerged as a key connector metabolite, linking the TCA cycle with amino acid and lipid metabolism (Sahlin et al., 1990; Betteridge, 2007; Campagna & Vignini, 2025).”
Current literature in diabetes
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The evidence behind early aggressive multi-drug treatment in type 2 diabetes
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Metadata
- Authors
- Betteridge, D. J.
- Affiliations
- University College Hospital (GB)
- Corresponding author
- Betteridge, D. John
- Venue
- Diabetes, Obesity and Metabolism
- Publisher
- Wiley
- Published
- 2007-02-26
- Volume
- 9
- Issue
- 5
- Pages
- 640-647
- ISSN
- 1462-8902 (ISSN-L)
- 1463-1326
- OpenAlex
- W2101667913
- Cited by
- 91
- References
- 27
- Citations by year
- 2026: 1 · 2025: 7 · 2024: 3 · 2023: 3 · 2022: 1 · 2021: 8 · 2020: 5 · 2019: 5 · 2018: 4 · 2017: 6 · 2016: 4 · 2015: 4 · 2014: 2 · 2013: 6 · 2012: 3
- FWCI
- 5.62
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Diabetes Obesity and Metabolism (publishedVersion)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
- Keywords
- pioglitazone, thiazolidinediones, type 2 diabetes, dyslipidemia, lipid metabolism, lipoprotein metabolism, HDL cholesterol, triglycerides, LDL particle size, insulin resistance, cardiovascular risk, statins, rosiglitazone
- MeSH terms
- Pioglitazone, Cardiovascular Diseases, Diabetes Mellitus, Type 2, Female, Humans, Hypoglycemic Agents, Lipids, Cholesterol, HDL, Cholesterol, LDL, Male, Triglycerides, Treatment Outcome, Metabolic Syndrome, Thiazolidinediones
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