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The drug dilemma of oral antidiabetic agents in pregnancy: Metformin
Published in Moshe Hod, Lois G. Jovanovic, Gian Carlo Di Renzo, Alberto de Leiva, Oded Langer, Textbook of Diabetes and Pregnancy, 2018
Yoel Toledano, Moshe Zloczower, Nicky Lieberman
Pharmacologic therapy may be helpful in preventing T2DM in high-risk patients (GDM) for whom lifestyle interventions fail or are not sustainable.120,121 Metformin is a pivotal therapy in this setting. To the best of our knowledge, there is only one randomized controlled trial of pharmacological therapy in women with prior GDM that considered diabetes prevention as the primary end point (the Troglitazone in Prevention of Diabetes [TRIPOD] study122). In this study, T2DM incidence reduced from 45% to 20% (RR 0.45) with troglitazone versus placebo. Troglitazone is not marketed anymore due to the risk of fatal liver failure.
Potential of Diet and Dietary Supplementation to Ameliorate the Chronic Clinical Perturbations of Metabolic Syndrome
Published in Stephen T. Sinatra, Mark C. Houston, Nutritional and Integrative Strategies in Cardiovascular Medicine, 2015
Harry G. Preuss, Dallas Clouatre
Troglitazone was used initially in a separate grouping in the DPP study described earlier. However, it was discontinued later when the drug was shown to be hepatotoxic.29 An article published in 2005 evaluated both the short-term results while the trial was active and the long-term results after troglitazone use was discontinued with the other trial groups.30 The troglitazone group ceased functioning after a mean of 0.9 years: at that time, the diabetes incident rate was 3.0 cases per 100 patient-years compared to 12.0 (placebo), 6.7 (metformin), and 5.1 (intensive lifestyle intervention) cases per 100 person-years in the other three groups. However, 3 years later after troglitazone withdrawal, the incidence rate for diabetes was no different than the placebo group. Therefore, troglitazone appeared effective only during the shortened period of actual use.
Pleural disease induced by drugs
Published in Philippe Camus, Edward C Rosenow, Drug-induced and Iatrogenic Respiratory Disease, 2010
Troglitazone, used in the treatment of insulin-resistant diabetes mellitus, has the most serious adverse effect of hepatic dysfunction. There is an isolated report of a 47-year-old man treated with troglitazone who developed cough, dyspnoea and night sweats after a week of therapy.52 Empirical antibiotics did not affect the symptoms. Chest radiograph showed small bilateral pleural effusions and basilar interstitial infiltrates. The patient’s symptoms abated within 24 hours after discontinuing troglitazone; however, complete resolution of the pleural effusions and parenchymal infiltrates did not occur for 6 days. Because of the temporal relationship between drug initiation and occurrence of the pleuropulmonary disease, a causal relationship was implied.
Potential molecular mechanism of action of sodium-glucose co-transporter 2 inhibitors in the prevention and management of diabetic retinopathy
Published in Expert Review of Ophthalmology, 2022
Lia Meuthia Zaini, Arief S Kartasasmita, Tjahjono D Gondhowiardjo, Maimun Syukri, Ronny Lesmana
Thiazolidinediones are insulin sensitizers that promote glucose uptake in skeletal muscle, improve peripheral insulin sensitivity and decrease plasma triglyceride levels. Troglitazone is effective for use in combination with insulin or other oral agents. However, the side effect of hepatotoxicity is reported after chronic treatment; thus, routine liver function monitoring is essential [6,7]. Insulin is by far the most potent glucose-lowering agent, specifically for patients with high hemoglobin A1c (HbA1c) levels whose glycemic control is suboptimal at maximal doses of oral agents. It can be used alone or in combination with oral antidiabetic medications. Common side effects of insulin therapy are weight gain and hypoglycemia. Therefore, self-monitoring of blood glucose is often necessary to adjust the doses, particularly in patients on multiple daily injections. Another drawback in initiating insulin therapy is the patient’s discomfort with self-injections [4,5].
Pharmacotherapeutic options for prediabetes
Published in Expert Opinion on Pharmacotherapy, 2021
Troglitazone was one of the initial treatment arms of the Diabetes Prevention Program. Although hepatotoxicity of troglitazone led to discontinuance of that study arm, the thiazolidinediones pioglitazone and rosiglitazone have been evaluated for the treatment of prediabetes. The ACT NOW trial studied 602 IGT patients randomized to pioglitazone or placebo. In a median follow-up period of 2.4 years, there was a reduction of 72% in attainment of diabetes diagnosis [57]. Conversion to normal glucose tolerance occurred in 48% of the patients in the pioglitazone group and 28% of those in the placebo group (P < 0.001). Other favorable findings in the piogitazone cohort included a 2 mm Hg decrease in diastolic blood pressure and a 31.5% decrease in carotid intima–media thickening (31.5%, P = 0.047). However, weight gain was greater with pioglitazone than with placebo (3.9 kg vs. 0.77 kg, P < 0.001), and edema was more frequent (12.9% vs. 6.4%, P = 0.007).
Thiazolidinedione drugs in the treatment of type 2 diabetes mellitus: past, present and future
Published in Critical Reviews in Toxicology, 2018
Melissa A. Davidson, Donald R. Mattison, Laurent Azoulay, Daniel Krewski
TZDs are synthetic ligands that were developed based on their affinity for the γ-subtype PPAR (with pioglitazone, but not rosiglitazone, also showing weak affinity for the α-subtype PPAR in vitro at concentrations higher than attained blood levels), with ligand-activated PPARγ acting as a transcription factor stimulating expression of genes involved in metabolic regulation through pathways of lipid storage and glucose homeostasis (Cantini et al. 2010; Hwang et al. 2011). The binding affinity of TZDs for PPARγ varies, with rosiglitazone and pioglitazone considered to be the most potent and most selective PPARγ agonists that have been marketed thus far. In vitro studies have shown that rosiglitazone has a 10-fold greater binding affinity than pioglitazone, which in turn has a 10-fold greater binding affinity than troglitazone, a drug that preceded both rosiglitazone and pioglitazone but was withdrawn from the US market for hepatotoxicity (Young et al. 1998; see Section 3.2). This is reflected in the differences in clinical dosage for these agents: 4 or 8 mg/day for rosiglitazone, 15–30 mg/day for pioglitazone (which may be increased in increments up to 45 mg/day), and 400–800 mg/day for troglitazone. A novel TZD drug, rivoglitazone, currently under development, is considered to be more potent than rosiglitazone or pioglitazone (Koffarnus et al. 2013). The initial recommended dose for rivoglitazone based on clinical trials conducted to date (Truitt et al. 2010; Kong et al. 2011; Chou et al. 2012) is 1 mg daily, increasing to a maximum dose of 2 mg daily.