Avandia scientific update |
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Indian J Med Res. 2007 Mar;125(3):389-98.
Misra P, Chakrabarti R.
Discovery Biology, Dr Reddy's Laboratories Ltd. - Discovery Research, Hyderabad, India.
The role of AMP kinase in diabetes.
The function of AMP activated protein kinase in diabetes. Type 2 diabetes is characterized by abnormal metabolism of glucose and fat, due in part to resistance to the
actions of insulin in peripheral tissues. If untreated it leads to several complications such as blindness, kidney
failure, neuropathy and amputations. The benefit of exercise in diabetic patients is well known and recent research
indicates that AMP activated protein kinase (AMPK) plays a major role in this exercise related effect. AMPK is
considered as a master switch regulating glucose and lipid metabolism. The AMPK is an enzyme that works as a fuel
gauge, being activated in conditions of high energy phosphate depletion. AMPK is also activated robustly by
skeletal muscle contraction and myocardial ischaemia, and is involved in the stimulation of glucose transport and
fatty acid oxidation produced by these stimuli. In liver, activation of AMPK results in enhanced fatty acid
oxidation and decreased production of glucose, cholesterol, and triglycerides. The two leading diabetic drugs
namely, metformin and rosiglitazone, show their metabolic effects partially through AMPK. These data, along with
evidence from studies showing that chemical activation of AMPK in vivo with 5-aminoimidazole-4-carboxamide
ribonucleoside (AICAR) improves blood glucose concentrations and lipid profiles, make this enzyme an attractive
pharmacological target for the treatment of type 2 diabetes and other metabolic disorders.
J Infect Dis. 2007 Jun 15;195(12):1754-61.
Cavalcanti RB, Raboud J, Shen S, Kain KC, Cheung A, Walmsley S.
Department of Medicine, University Health Network, Toronto, ON, M5T 2S8, Canada. Rodrigo.
A Randomized, Placebo-Controlled Trial of Rosiglitazone for HIV-Related Lipoatrophy.
HIV-Related Lipoatrophy using Rosiglitazone: a randomized, placebo-controlled trial.
Background. Thiazolidinediones such as rosiglitazone may have benefit in ameliorating human immunodeficiency virus
(HIV) lipoatrophy.Methods. HIV-positive patients receiving stable, protease inhibitor-containing highly active
antiretroviral therapy with HIV lipodystrophy were prospectively randomized to rosiglitazone (4 mg/day) or placebo.
The primary end point was the 24-week percentage change in arm fat by dual-energy x-ray absorptiometry (DEXA).
Clinical and anthropometric evaluations, fasting lipid parameters, oral glucose tolerance testing, CD36 expression,
quality of life measures, and DEXA scanning were performed at baseline and week 24.Results. Seventy-eight of the 96
enrolled patients were evaluated. Median age was 46.8 years, 97.4% were male, and 54% were treated with thymidine
analogues. Median baseline limb fat was 3.76 and 2.99 kg in the rosiglitazone and control groups, respectively.
Median changes in arm, leg, trunk, and total body fat at 24 weeks were not significantly different between groups
(7.1% vs. 5.0% [P=.94]; 0.1% vs. -2.4% [P=.90]; 1.2% vs. -1.4% [P=.81]; and 1.7% vs. 0.4% [P=.76]). There were no
significant changes in secondary end points. There was no correlation between changes in body fat or treatment-arm
and CD36 expression.Conclusions. This randomized, placebo-controlled trial did not show benefit of 4 mg/day of
rosiglitazone on lipoatrophy or metabolic parameters in patients with HIV lipodystrophy.
Int J Gynaecol Obstet. 2006 Sep 27;
Lanham MS, Lebovic DI, Domino SE.
Department of Obstetrics and Gynecology, University of Michigan, Ann Arbor, Michigan, USA.
Contemporary medical therapy for polycystic ovary syndrome.
Efficacy of medical therapy for the treatment of polycystic ovary syndrome. Polycystic ovary syndrome is a multi-system endocrinopathy with long-term metabolic and cardiovascular health consequences. Patients typically present due to symptoms of irregular menstruation, hair growth, or infertility; however, recent management options are aimed at further treating underlying glucose-insulin abnormalities as well as androgen excess for proactive control of symptoms. By a 2003 international consensus conference, diagnosis is made by two out of three criteria: chronic oligoovulation or anovulation after excluding secondary causes, clinical or biochemical evidence of hyperandrogenism (but not necessarily hirsutism due to inter-patient variability in hair follicle sensitivity), and radiological evidence of polycystic ovaries. Traditional medical treatment options include oral contraceptive pills, cyclic progestins, ovulation induction, and anti-androgenic medications (aldosterone antagonist, 5alpha-reductase antagonist, and follicle ornithine decarboxylase inhibitor). Recent pharmacotherapies include insulin-sensitizing medications metformin and two thiazolidinediones (rosiglitazone/Avandia(R) and pioglitazone/Actos(R)), a CYP19 aromatase inhibitor (letrozole/Femara(R)), and statins to potentially lower testosterone levels.
J Clin Endocrinol Metab. 2004 Dec;89(12):6048-53.
Smith SA, Porter LE, Biswas N, Freed MI.
Scientific Affairs, Diabetes, GlaxoSmithKline, Harlow, Essex, CM19 5AW, United Kingdom.
Rosiglitazone, but not glyburide, reduces circulating proinsulin and the proinsulin:insulin ratio in type 2 diabetes.
Proinsulin:insulin ratio and proinsulin circulation in type 2 diabetes patients can be reduced by taking Rosiglitazone, but glyburide can’t. An elevation in the ratio of proinsulin (PI) to immunoreactive insulin (IRI) is inversely related to beta-cell function in type 2 diabetes, and increased PI is an independent risk factor for coronary heart disease. An objective of the present studies was to assess the effects of the thiazolidinedione insulin sensitizer, rosiglitazone, on indirect markers of beta-cell function and cardiovascular risk in people with type 2 diabetes by measuring plasma PI and the PI:IRI ratio. Parameters of insulin processing, including plasma PI and PI:IRI ratios, were determined in type 2 diabetes patients enrolled in two randomized double-blind studies comparing the effects of rosiglitazone (4 or 8 mg/d) with placebo (study 1, 26-wk treatment) or the sulfonylurea glyburide (study 2, 52-wk treatment). Treatment with rosiglitazone for 26 wk (study 1) produced significant dose-dependent decreases in both plasma PI concentrations (18-29%) and the PI:IRI ratio compared with baseline (7-14%) and placebo (19-29%) (P < 0.001). A significant increase in the PI:IRI ratio in placebo-treated patients occurred (P < 0.001). In study 2, rosiglitazone also significantly reduced both plasma PI and the PI:IRI ratio compared with baseline (P < 0.001). In contrast, glyburide significantly increased both plasma PI (45%; P < 0.001) and the PI:IRI ratio (10%) (P < 0.05 vs. baseline). These results show that rosiglitazone and glyburide have differential effects on absolute PI levels and the PI:IRI ratio in people with type 2 diabetes.
Vnitr Lek. 2004 Nov;50(11):818-24.
Perusicova J, Haas T.
Diabetologicke centrum, III. interni klinika 1. lekarske fakulty UK a VFN, Praha.
[Rosiglitazon in treatment of Type II diabetes mellitus--experience of diabetologists in the Czech Republic. Part I: compensation of diabetes, sugar metabolism] [Article in Czech]
Efficacy of Rosiglitazon in the treatment of Type II diabetes mellitus – comments of Czech Republic diabetologists. Phase I: compensation of diabetes in sugar metabolism. Thiazolidindione derivates (glitazones) make a very promising group of peroral antidiabetic drugs. They are represented by rosiglitazon which is available on our market to type II diabetics. As far as sugar metabolism is concerned, rosiglitazon can reduce glycaemia and insulin level both when fasting and postprandially. GOAL: The goal of the authors' work was to gain their own experience with rosiglitazon treatment in type II diabetics in the Czech Republic. Sample: The monitored sample consisted of 388 patients with insufficiently compensated type II diabetes when treated by sulphonylurea compounds or metformine. METHODS: 95 diabetologists from diabetology medical offices started a 6-month-long treatment with rosiglitazon (Avandia) dose of 4 mg a day as stated in European recommendations. In order to assess changes in sugar metabolism (compensation of diabetes) glycaemia and C peptide were monitored when fasting and postpradially and HbA1c was monitored in 2-month-long intervals. RESULTS: Weight, waist-hip ratio (WHR) and C-peptide levels remained unchanged. Statistically significant (p < 0.0001) was a HbA1c decrease over 6 month from 9.61% to 8.48%. Fasting glycaemia decreased by 2.49 and postprandial glycaemia by 2.71 mmol/l. No significant side effects were identified. CONCLUSION: Rosiglitazon administration combined with administration of sulphonylurea compounds or metformine significantly improved compensation of diabetes compared to initial therapy.
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Drug category:Antidiabetic agents
 Avandia scientific update
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