Meta-Analysis for Rare Events
Ding-Geng (Din) Chen, Karl E. Peace in Applied Meta-Analysis with R and Stata, 2021
In a meta-analysis for the effect of rosiglitazone on the risk of myocardial infarction (MI) and death from cardiovascular causes, Nissen and Wolski (2007) searched the available published literature and found 116 potentially relevant studies where 42 of these met the inclusion criteria. Data were then extracted from the 42 publications and combined using a fixed-effects meta-analysis model. This yielded an OR for the rosiglitazone group to the control group of 1.43 with 95% confidence interval (CI) of (1.03, 1.98) and p-value = 0.03 for MI; and 1.64 with 95% CI of (0.98, 2.74) and p-value = 0.06 for death from cardiovascular causes. Based on these results, the authors concluded that rosiglitazone use was statistically significantly associated with the risk of MI and was borderline statistically significant with death from cardiovascular causes. Therefore, using rosiglitazone for the treatment of Type 2 diabetes could lead to serious adverse cardiovascular effects.
Diabetes and the heart
Clive Handler, Gerry Coghlan, Marie-Anne Essam in Preventing Cardiovascular Disease in Primary Care, 2018
Thiazolidinediones (rosiglitazone, pioglitazone) reduce peripheral insulin resistance. They are used alone or with metformin or a sulphonylurea in patients who cannot tolerate a combination of metformin and sulphonylurea, or in whom either metformin or a sulphonylurea is contraindicated. They are also used as add-on therapy for patients with high glycated haemoglobin levels despite maximum doses of metformin plus a sulphonylurea. Some endogenous insulin secretion is essential. Thiazolidinediones have similar efficacy as insulin in decreasing glycated haemoglobin by two percentage points, but are more expensive. Weight gain (3-4 kg) and gastrointestinal side effects may occur, but HDL cholesterol levels increase by 10%. Thiazolidinediones are contraindicated in inflammatory bowel disease and severe hepatic and renal disease, and there is an increased risk of oedema, congestive heart failure, and fractures in women. There is uncertainty about the safety of rosiglitazone in patients with coronary heart disease. Pioglitazone is preferred to rosiglitazone for patients with coronary heart disease and those who have more than one cardiovascular risk factor.
Use of oral hypoglycemic agents in pregnancy
Moshe Hod, Lois G. Jovanovic, Gian Carlo Di Renzo, Alberto de Leiva, Oded Langer in Textbook of Diabetes and Pregnancy, 2018
Rosiglitazone and pioglitazone, other oral agents in this group, are more potent than troglitazone and claim to offer lower risk of hepatotoxicity. They are absorbed within 2 hours but the maximum clinical effect is not observed for 6–12 weeks. Liver function should be measured before the start of therapy and monitored once initiated. Studies also report considerable weight gain with the drugs.45,46 Similarities exist between rosiglitazone and glyburide in pharmacological characteristics that may suggest that there is a possibility that they minimally cross the placenta. If this proves to be the case, rosiglitazone and pioglitazone, just as glyburide and metformin, may be ideal agents for the management of GDM and type 2 diabetes in pregnancy, as a single therapy or in combination with glyburide.
Effects of ginkgo leaf tablet on the pharmacokinetics of rosiglitazone in rats and its potential mechanism
Published in Pharmaceutical Biology, 2022
Xueting Xing, Mengzhu Kong, Qiaoyu Hou, Jiaqi Li, Wen Qian, Xijing Chen, Hanhan Li, Changqing Yang
Rosiglitazone (ROS), a thiazolidinedione insulin sensitiser, could be used for the treatment of type 2 diabetes mellitus due to the enhanced sensitivity of peripheral tissue to insulin and improved utilisation of glucose through activating peroxisome proliferator‑activated receptor γ (Dawed et al. 2016; Matsumoto et al. 2019; Ren et al. 2020; Zhou et al. 2021). It is rapidly absorbed, almost completely bioavailable from the gastrointestinal tract (Cox et al. 2000). ROS is metabolised mainly by CYP2C8 via N-demethylation and p-hydroxylation and by CYP2C9 to a lesser extent in the human liver (Naik et al. 2012; Wring et al. 2018). The metabolites are considerably less potent than the parent form (Park et al. 2004). Therefore, modulation of CYP2C8 or CYP2C9 activities may play a vital role in the pharmacokinetic profiles of ROS.
Management of obesity in adolescents with polycystic ovary syndrome
Published in Expert Opinion on Pharmacotherapy, 2020
Anastasia Vatopoulou, Konstantinos Tziomalos
In a randomized study (n = 46), neither rosiglitazone nor OCP (30 μg of ethinyl estradiole and 3 mg of drosperinone) given for 6 months had an effect on body weight, waist circumference, fat mass or percent body fat [29]. However, rosiglitazone decreased visceral adiposity [29]. Both treatments improved menstruation to a similar degree [29]. Both treatments also reduced androgen levels but the reduction was greater with OCP [29]. Both treatments also increased adiponectin levels but the increase was greater with rosiglitazone [29]. In addition, only rosiglitazone improved insulin sensitivity and reduced TG levels [29]. On the other hand, only the OCP increased HDL-C levels but also increased total cholesterol and hsCRP levels as well as diastolic blood pressure at night [29]. Neither treatment had an effect on pulse wave velocity or on carotid intima media thickness [29].
Peroxisome proliferator-activated receptor-gamma (PPARγ) and its immunomodulation function: current understanding and future therapeutic implications
Published in Expert Review of Clinical Pharmacology, 2022
Carlos Antonio Trindade da Silva, Juliana Trindade Clemente-Napimoga, Henrique Ballassini Abdalla, Rosanna Tarkany Basting, Marcelo Henrique Napimoga
The high-affinity synthetic ligands of PPARγ receptors are characterized by the drug class of the thiazolidinediones (TZDs) [38]. The TZDs target insulin resistance in type 2 diabetes mellitus, enhancing insulin sensitivity [39]. There are two commercial drugs on the market, pioglitazone and rosiglitazone [39]. The most common collateral effects of TZDs include fluid retention, weight gain and adipogenesis, inflammation in cardiovascular tissues, bone loss, and atherosclerosis [39–42]. The concerns about the adverse effects result in rosiglitazone being withdrawn from the European market in 2010 [40,43]. The United States Food and Drug Administration (FDA) restricted access to rosiglitazone in 2011 but removed its prescribing restrictions in 2013. More recently, new data show that TZD, main pioglitazone, reduces myocardial infarctions and ischemic strokes and is a useful tool in the arsenal for clinical use [44,45].
Related Knowledge Centers
- Glimepiride
- Metformin
- Myocardial Infarction
- Type 2 Diabetes
- Insulin
- Diabetes Medication
- Peroxisome Proliferator-Activated Receptor
- Meta-Analysis
- Glycated Hemoglobin
- Boxed Warning