Side Effects of pioglitazone: A Synthesis of Findings from 27 Studies

  1. Home
  2. Side Effects of pioglitazone
This information is not medical advice and is not a substitute for diagnosis or treatment by a physician.Data sources and disclaimers (data limitations, copyright, etc.)The analysis on "Side Effects of pioglitazone: A Synthesis of Findings from 27 Studies" on this page is based on PubMed data provided by the U.S. National Library of Medicine (NLM). However, NLM does not endorse or verify these analyses.

This analysis is based on research papers included in PubMed, but medical research is constantly evolving and may not fully reflect the latest findings. There may also be biases towards certain research areas.

This information is not medical advice and is not a substitute for diagnosis or treatment by a physician. If you have concerns about "Side Effects of pioglitazone: A Synthesis of Findings from 27 Studies", please consult your doctor.

For NLM copyright information, please see Link to NLM Copyright Page
PubMed data is obtained via Hugging Face Datasets: Link to DatasetPlease check the disclaimer.
This page's analysis is based on PubMed data provided by the U.S. National Library of Medicine (NLM).
Original Abstract of the Article

Major Research Findings

Pioglitazone is a medication used to treat diabetes, but several side effects have been reported. This review presents the latest research findings on the side effects of pioglitazone.

According to a study in 12 , pioglitazone may be an effective treatment for psoriasis. Another study in 2 showed that pioglitazone has protective effects against diet-induced dyslipidemia and vascular inflammation. However, a study in 15 suggests that pioglitazone may also have negative effects on bones.

Reasons for side effects

The side effects of pioglitazone are mainly thought to be due to the activation of peroxisome proliferator-activated receptor gamma (PPARγ). PPARγ is involved in various cellular functions such as adipocyte differentiation, insulin sensitivity regulation, and inflammatory responses. Pioglitazone activates PPARγ, leading to increased insulin sensitivity and reduced blood glucose levels. However, PPARγ activation can also lead to side effects such as weight gain, edema, and osteoporosis.

Common side effects

Weight Gain

Pioglitazone can promote adipocyte differentiation and cause weight gain by activating PPARγ. 7 shows that pioglitazone promotes adipocyte differentiation. Additionally, a study in 17 suggests that pioglitazone may inhibit the function of mitochondria in the myocardium, potentially leading to heart failure. Furthermore, a study in 23 demonstrated that pioglitazone promotes lipid accumulation in adipocytes and white adipose tissue.

Edema

Pioglitazone can cause edema by activating PPARγ, making the body's tissues more prone to retaining water. A study in 27 demonstrated that pioglitazone increases the expression of AQP2 and AQP3, which promote water reabsorption in the kidneys, potentially leading to edema. Another study in 8 reported that while pioglitazone can reduce liver fat accumulation, it can also have side effects such as edema.

Osteoporosis

Pioglitazone may cause osteoporosis by inhibiting bone formation and promoting bone resorption. A study in 15 suggests that pioglitazone increases the accumulation of bone marrow adipocytes, which may increase the risk of osteoporosis. Another study in 4 found that pioglitazone has a greater negative impact on bones compared to other diabetes medications.

Other side effects

Besides the above, other side effects such as liver dysfunction, heart failure, and bladder cancer have been reported for pioglitazone. A study in 10 recommends combination therapy with other diabetes medications to reduce the side effects of pioglitazone. In another study in 21 , PXL065, a derivative of pioglitazone with suppressed PPARγ activity, was developed to mitigate the side effects of pioglitazone.

Countermeasures for side effects

Weight Gain

Lifestyle modifications such as dietary changes and exercise are essential to prevent weight gain. A study in 6 indicated that lifestyle changes are crucial in reducing the side effects of pioglitazone. Additionally, a study in 14 developed a drug delivery system using nanoparticles to reduce the side effects of pioglitazone.

Edema

Measures such as limiting salt intake and sleeping with your legs elevated can help prevent edema. A study in 27 found that combination therapy with SGLT2 inhibitors can effectively reduce the side effects of pioglitazone. In another study in 9 , a new drug called clofazimine was developed to mitigate the side effects of pioglitazone.

Osteoporosis

Consuming calcium and vitamin D, exercising, and, if necessary, taking osteoporosis medication are important measures to prevent osteoporosis.

Comparison between studies

Common points

These studies show that pioglitazone is effective in treating diabetes by activating PPARγ, but it may cause side effects such as weight gain, edema, and osteoporosis.

Differences

The incidence and severity of side effects vary depending on the study. This may be due to differences in the animal species, doses, and study durations used. The methods for reducing the side effects of pioglitazone also vary from study to study. Therefore, further research is needed on the side effects of pioglitazone.

Points to note regarding application to real life

Pioglitazone is an effective medication for treating diabetes, but several side effects have been reported. If you are considering taking pioglitazone, consult your doctor to discuss the risks of side effects, countermeasures, and the importance of understanding them before taking the medication.

Limitations of current research

Research on the side effects of pioglitazone is still insufficient. In particular, the long-term effects of pioglitazone are still poorly understood. Further research is also needed on ways to reduce the side effects of pioglitazone.

Future research directions

To develop ways to mitigate the side effects of pioglitazone, there is a need for the development of medications that suppress PPARγ activation and the development of drug delivery systems for pioglitazone. Research is also needed to investigate the long-term effects of pioglitazone.

Conclusion

Pioglitazone is an effective medication for treating diabetes, but several side effects have been reported. Research on the side effects of pioglitazone is still insufficient. Therefore, if you are considering taking pioglitazone, consult your doctor to discuss the risks of side effects, countermeasures, and the importance of understanding them before taking the medication.

Literature analysis of 27 papers
Positive Content
26
Neutral Content
0
Negative Content
1
Article Type
2
0
0
6
27
1.

[Rediscovery of pioglitazone].

Author: PokolyBence, SomogyiAnikó

Cardiovascular benefits
Metabolic benefits
Possible side effects

Pioglitazone, a thiazolidinedione, has been shown to reduce the risk of cardiovascular complications in type 2 diabetes. However, its use has declined in recent years due to potential side effects. This paper summarizes the evidence for pioglitazone and discusses its benefits and risks.

English AbstractA summary of a research paper/publication written in English for a wider audience.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : Hungarian

3.

Can a selective PPARγ modulator improve glycemic control in patients with type 2 diabetes with fewer side effects compared with pioglitazone?

Author: DePaoliAlex M, HigginsLinda S, HenryRobert R, MantzorosChristos, DunnFredrick L,

Type 2 diabetes treatment

INT131 besylate, a potent, nonthiazolidinedione, selective peroxisome proliferator-activated receptor γ (PPARγ) modulator, aims to improve glucose metabolism while minimizing the side effects of full PPARγ agonists. This study compared the effectiveness and side effects of INT131 besylate versus 45 mg pioglitazone HCl in individuals with type 2 diabetes.

Comparative StudyResearch that compares multiple groups/interventions to determine differences/similarities in outcomes/characteristics.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
Research Support, U.S. Gov't, Non-P.H.S.Research funding provided by US government agencies other than the Public Health Service.

Language : English

4.

Effects of different insulin sensitisers in the management of polycystic ovary syndrome: A systematic review and meta-analysis.

Author: MelinJohanna M, ForslundMaria, AlesiSimon J, PiltonenTerhi, RomualdiDaniela, SpritzerPoli M, TayChau Thien, PenaAlexia S, WitchelSelma F, MousaAya, TeedeHelena J

Improved insulin sensitivity

This study compared the effects of metformin, rosiglitazone, and pioglitazone in managing polycystic ovary syndrome (PCOS) to inform the 2023 International Evidence-based PCOS Guideline.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

7.

Screening for PPAR Non-Agonist Ligands Followed by Characterization of a Hit, AM-879, with Additional No-Adipogenic and cdk5-Mediated Phosphorylation Inhibition Properties.

Author: Ribeiro FilhoHelder Veras, Bernardi VideiraNatália, BridiAline Villanova, TittanegroThais Helena, Helena BatistaFernanda Aparecida, de Carvalho PereiraJosé Geraldo, de OliveiraPaulo Sérgio Lopes, BajgelmanMarcio Chaim, Le MaireAlbane, FigueiraAna Carolina Migliorini

Antidiabetic properties
Heart failure
Liver disease
Weight gain

This study identified a novel non-agonist PPARγ ligand, AM-879, that binds to the receptor without activating it. Unlike traditional PPARγ agonists, AM-879 does not induce adipocyte differentiation or alter gene expression associated with adipogenesis. It inhibits CDK5-mediated phosphorylation of PPARγ, suggesting a potential mechanism for its antidiabetic effects.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

9.

Leprosy drug clofazimine activates peroxisome proliferator-activated receptor-γ and synergizes with imatinib to inhibit chronic myeloid leukemia cells.

Author: KumarHarish, ChattopadhyaySourav, DasNabanita, ShreeSonal, PatelDinesh, MohapatraJogeswar, GurjarAnagha, KushwahaSapana, SinghAbhishek Kumar, DubeyShikha, LataKiran, KushwahaRajesh, MohammedRiyazuddin, DastidarKrishnarup Ghosh, YadavNamrata, VishwakarmaAchchhe Lal, GayenJiaur Rahaman, BandyopadhyaySanghamitra, ChatterjeeAbhijit, JainMukul Rameshchandra, TripathiAnil Kumar, TrivediArun Kumar, ChattopadhyayNaibedya, RamachandranRavishankar, SanyalSabyasachi

Treat CML

This study identifies clofazimine, a leprosy drug, as a potential treatment for chronic myeloid leukemia (CML). Clofazimine induced apoptosis of blood mononuclear cells from CML patients, particularly in imatinib-resistant cells. Combining clofazimine with imatinib showed synergistic efficacy in a K562 xenograft study. Clinical evaluation of clofazimine in imatinib-refractory CML is suggested.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

10.

Practical strategies for improving outcomes in T2DM: The potential role of pioglitazone and DPP4 inhibitors.

Author: Del PratoStefano, ChiltonRobert

Preservation of beta-cell function
Sustained glucose-lowering effect

Type 2 diabetes mellitus (T2DM) is a complex disease with multiple pathogenic defects contributing to hyperglycemia. This review discusses the potential for early combination therapy of pioglitazone and dipeptidyl peptidase-4 inhibitors (DPP4i) in managing T2DM.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

11.

An apoptotic body-biomimic liposome in situ upregulates anti-inflammatory macrophages for stabilization of atherosclerotic plaques.

Author: WuYue, ZhangYong, DaiLiLi, WangQianQian, XueLingJing, SuZhigui, ZhangCan

Atherosclerosis treatment
None

Apoptotic bodies, which are naturally occurring cell fragments, are effectively taken up by macrophages. This study developed an apoptotic body biomimic liposome (AP-Lipo) to deliver pioglitazone (PIO), an anti-inflammatory drug, specifically to macrophages in atherosclerotic plaques. AP-Lipo showed improved ability to target activated vascular endothelial cells and pro-inflammatory macrophages, leading to reduced inflammation and potentially slowing atherosclerosis progression.

Comparative StudyResearch that compares multiple groups/interventions to determine differences/similarities in outcomes/characteristics.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

12.

Peroxisome proliferator-activator receptor γ and psoriasis, molecular and cellular biochemistry.

Author: LinXiran, MengXianmin, SongZhiqi, LinJingrong

Psoriasis treatment
Side effects

Peroxisome proliferator-activated receptor γ (PPARγ) plays a role in the pathogenesis of psoriasis. PPARγ agonists, like pioglitazone, show promise for treating psoriasis, but concerns remain regarding potential side effects. Natural products with PPARγ-activating potential are being explored as potential therapeutic agents.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

15.

Novel thiazolidinedione analog reduces a negative impact on bone and mesenchymal stem cell properties in obese mice compared to classical thiazolidinediones.

Author: BenovaAndrea, FerencakovaMichaela, BardovaKristina, FundaJiri, ProchazkaJan, SpoutilFrantisek, CajkaTomas, DzubanovaMartina, BalcaenTim, KerckhofsGreet, WillekensWouter, van LentheG Harry, AlquicerGlenda, PecinovaAlena, MracekTomas, HorakovaOlga, RossmeislMartin, KopeckyJan, TencerovaMichaela

Reduced TZD side effects
Bone loss
Bone marrow adipocyte accumulation
Fracture risk

This abstract discusses the potential side effects of thiazolidinediones (TZDs), a class of drugs used to treat diabetes. TZDs can increase the accumulation of bone marrow adipocytes, leading to a higher fracture risk and bone loss. The abstract explores the effect of a novel TZD analog, MSDC-0602K, on bone phenotype and bone marrow mesenchymal stem cells in relation to obesity.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

16.

Randomised cross-over trial of vildagliptin and pioglitazone as add-on therapy in patients with type 2 diabetes: predicting Which One is Right Here (WORTH) study protocol.

Author: YeuRui Qian, BrandonRebecca, JiangYannan, GriffithsDale, SmallmanKate, MoffittAllan, DohertyGlenn, PaulRyan, Harré HindmarshJennie, MerrimanTony R, Macaskill-SmithKerry, Orr-WalkerBrandon, MurphyRinki

Glucose control

This study investigates whether the glycemic response to vildagliptin (a dipeptidyl peptidase-4 inhibitor) and pioglitazone (a thiazolidinedione), common diabetes medications, varies based on ethnicity, gender, obesity, triglyceride levels, or genetic variations.

Clinical Trial ProtocolA plan for conducting a clinical trial. It describes in detail the purpose, design, methodology, and statistical considerations of the trial, ensuring the transparency and consistency of the trial.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

17.

PPARγ-Independent Side Effects of Thiazolidinediones on Mitochondrial Redox State in Rat Isolated Hearts.

Author: RiessMatthias L, ElorbanyReem, WeihrauchDorothee, StoweDavid F, CamaraAmadou K S

Cardiac ischemia/reperfusion injury
Heart failure

This study investigated the effects of thiazolidinediones (TZDs), a class of anti-diabetic drugs, on myocardial and mitochondrial function in isolated rat hearts. The study found that rosiglitazone administration before ischemia-reperfusion (IR) increased IR injury. Both rosiglitazone and pioglitazone caused excessive mitochondrial uncoupling, suggesting that TZDs may enhance myocardial IR injury through mitochondrial dysfunction.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, N.I.H., ExtramuralResearch funding provided by the NIH to external research institutions and researchers.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.
Research Support, U.S. Gov't, Non-P.H.S.Research funding provided by US government agencies other than the Public Health Service.

Language : English

21.

Evaluation of PXL065 - deuterium-stabilized (R)-pioglitazone in patients with NASH: A phase II randomized placebo-controlled trial (DESTINY-1).

Author: HarrisonStephen A, ThangCarole, BolzeSébastien, DewittSheila, Hallakou-BozecSophie, DubourgJulie, BedossaPierre, CusiKenneth, RatziuVlad, GrouinJean-Marie, MollerDavid E, FouquerayPascale

Improved safety profile
NASH treatment

Pioglitazone (Pio) is a drug effective for treating non-alcoholic steatohepatitis (NASH), but it can have side effects. PXL065, a deuterium-stabilized version of R-Pio, lacks the PPARγ activity that causes side effects while retaining other beneficial effects. This study aims to evaluate PXL065's efficacy and safety in NASH patients, hoping for a better safety profile than Pio.

Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
Clinical Trial, Phase IIA Phase II trial is a trial that further evaluates the efficacy and safety of a new drug or treatment, whose safety has been confirmed to some extent in a Phase I trial, in a small number of patients.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

22.

Premedication with pioglitazone prevents doxorubicin-induced left ventricular dysfunction in mice.

Author: FurihataTakaaki, MaekawaSatoshi, TakadaShingo, KakutaniNaoya, NambuHideo, ShirakawaRyosuke, YokotaTakashi, KinugawaShintaro

DOX cardiotoxicity prevention

Doxorubicin (DOX), a widely used chemotherapy drug, can cause cardiac toxicity. This study explores the potential of pioglitazone, a drug currently contraindicated in heart failure, as a premedication before DOX treatment to mitigate cardiac toxicity in mice.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

23.

Selective modulator of nuclear receptor PPARγ with reduced adipogenic potential ameliorates experimental nephrotic syndrome.

Author: BryantClaire, RaskGalen, WallerAmanda P, WebbAmy, Galdino-PittaMarina R, AmatoAngelica A, CiancioloRachel, GovindarajanRajgopal, BecknellBrian, KerlinBryce A, NevesFrancisco A R, FornoniAlessia, AgrawalShipra

Reduced hypercoagulopathy
Reduced hypoalbuminemia
Reduced proteinuria
Lipid accumulation
aP2 induction

This study compares the therapeutic effects of GQ-16, a selective modulator of PPARγ, and pioglitazone, a traditional PPARγ agonist, in a pre-clinical nephrotic syndrome (NS) model. The study found that GQ-16 more effectively reduced proteinuria, NS-associated comorbidities, and adipogenic side effects compared to pioglitazone.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

25.

Design, synthesis and biological evaluation of novel 5-(imidazolyl-methyl) thiazolidinediones as antidiabetic agents.

Author: ShakourNeda, SahebkarAmirhossein, KarimiGholamreza, PasebanMaryam, TasbandiAida, MosaffaFatemeh, Tayarani-NajaranZahra, GhodsiRazieh, HadizadehFarzin

Anti-diabetic activity
No significant side effects

A new series of imidazolyl-methyl-l-2,4-thiazolidinediones showed anti-hyperglycemic activity in a diabetic-control group, without toxicity in 3T3 cells. Compounds 9e and 9b were more effective than pioglitazone at lowering blood glucose and showed similar PPAR-γ gene expression behavior.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

26.

Current and Emerging Approaches for Nonalcoholic Steatohepatitis Treatment.

Author: ChenMing-Ming, CaiJing-Jing, YuYao, SheZhi-Gang, LiHongliang

NASH treatment
Side effects

NASH is a serious liver disease with no FDA-approved treatments. While lifestyle modifications are recommended, they are often difficult to maintain and may not be enough to cure NASH. Bariatric surgery is effective for morbidly obese patients with NASH. Several pharmacological agents are being investigated for NASH treatment, with some showing promising results in clinical trials. Further research is needed to assess their long-term effects and establish effective therapies.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

This site uses cookies. Visit our privacy policy page or click the link in any footer for more information and to change your preferences.