New use of old drugs (Metformin & AICAR ) in treating hepatitis C...

In continuation of my update on Metformin...

Researchers from  University of Leeds have found drugs such as antidiabetic  drug  Metformin  (right  structure)  and                AICAR, (5-Amino-4-imidazole carboxamide ribonucleotide) below right structure) used to combat obesity, can prevent the hepatitis C virus from replicating in the body.

Drugs such as Metformin and AICAR work by stimulating an enzyme called AMP kinase (AMPK) which regulates energy within our cells,  the very enzyme that hepatitis C virus represses to enable it to replicate. As per the claim by the researchers, the hepatitis C virus switches off AMPK so that the cell continues production of lipids and membranes, both of which are vital to its survival. 

AMPK's usual function is to conserve the energy balance in cells (it does by temporarily shutting down the production of lipids (fats) and membranes) when it senses an increase in energy requirements. Researchers  claim that, when a cell becomes infected by a virus,  AMPK gets activated and  shuts down certain functions of the cell temporarily until the cell's energy is rebalanced. 

Building on this finding, the research team were able to examine how cells would react when treated with common drugs that stimulate AMPK. They found that in infected cells, the drugs were able to halt virus replication, enabling cells to clear the infection...

"We're very excited about these findings," says Professor Mark Harris from the University's Faculty of Biological Sciences. "These drugs are already on the market, and whilst substantial clinical trials still need to take place before they can be used to treat hepatitis C infection, we think it could be an enormous step forward in the battle against the virus."  ....

Ref : http://www.leeds.ac.uk/news/article/825/new_use_for_old_drugs_in_treating_hepatitis_c?research

Metformin helps dieting teens to lose weight....

We know that Metformin  (see structure), is a  biguanide hypoglycemic  agent used in the treatment of non-insulin-dependent diabetes mellitus not responding to dietary modification. Metformin improves glycemic control by improving insulin sensitivity and decreasing intestinal absorption of glucose. Metformin's pharmacologic mechanisms of action are different from other classes of oral antihyperglycemic agents. Metformin decreases hepatic glucose production, decreases intestinal absorption of glucose and improves insulin sensitivity by increasing peripheral glucose uptake and utilization. In my earlier blogs, I have covered the recent (findings)  updates on metformin.

Now researchers  lead by Dr. Darrell Wilson (from Division of Pediatric Endocrinology and Diabetes, Stanford University)  have found that metformin appears to help overweight teenagers lose weight when combined with a program designed to help them change their lifestyle habits.

As per the claim by the authors though metformin hydrochloride is  used as a primary or adjunctive treatment in obese  nondiabetic adolescents there are limited short-term data to support this therapy  and also it is unclear whether any observed effects of metformin on body mass index. Therefore  the researchers conducted a 48-week randomized, double-blind, placebo-controlled trial of extended-release (XR) metformin therapy in nondiabetic obese adolescents  followed by a 48-week monitoring period after completion of treatment.

Researchers found that the addition of metformin to a lifestyle change intervention for a period of 12 months resulted in a significant improvement of BMI regardless of baseline fasting insulin levels, that persisted for 12 to 24 weeks after cessation of drug treatment. The mean (SE) reduction in BMI of –1.1 (0.5) at 1 year was comparable with that observed in other randomized controlled trials of metformin treatment in obese adolescents, although these randomized controlled trials involved shorter treatment duration (about 6 months), targeted obese children with additional diabetes risks, and had smaller sample sizes.

The mechanisms of action for these effects have not fully been elucidated but may involve beneficial effects on carbohydrate and lipid metabolism, mediated through adenosine monophosphate kinase.

Researchers conclude that  "metformin  in combination with lifestyle modification, had a small but statistically significant effect to reduce BMI in obese adolescents; this effect waned within 12 to 24 weeks of discontinuing metformin treatment". These results indicate that metformin may have an important role in the treatment of adolescent obesity. Longer-term studies will be needed to define the effects of metformin treatment on obesity-related disease risk in this population....

Ref : http://archpedi.ama-assn.org/cgi/content/full/164/2/116?home

Metformin - safe for patients with advanced heart failure and diabetes mellitus

In continuation of my update on Metformin,   I am sharing herewith  something interesting info,  about the same drug. Now researchers from David Geffen School of Medicine at UCLA,  have found that metformin, a drug often used in the treatment of diabetes mellitus, is safe for use in treating patients who have both diabetes and advanced heart failure. 

Diabetes increases not only the risk of developing heart failure, but also the risk of death among heart failure patients. This is due in large part to the fact that diabetes, because it increases the amounts of sugar and fat circulating in the bloodstream, accelerates the onset of coronary atherosclerosis. This hardening and thickening of blood vessels is the hallmark of atherosclerotic heart disease, the most common cause of death. The optimal treatment for high glucose and fat blood levels among heart failure patients has not been demonstrated.

The new study involved 401 patients of an average age of 56, with type II diabetes and advanced systolic heart failure. This patient cohort was followed for 14 years in a comprehensive heart failure management program.

The study results suggest that, in patients with both advanced heart failure and diabetes, use of metformin is safe, and may be associated with better heart failure survival.

Interestingly, the diabetes drug metformin previously carried a "black box warning" from the FDA against its use in treating diabetes in heart failure patients and that is why most many physicians have been reluctant to use metformin and other similar medications to treat this patient group. However, analysis by the researchars, shows that using metformin to treat diabetes in patients with advanced, systolic heart failure is not only safe, but may also play a role in improving outcomes compared to conventional diabetes care. As per the claim by Dr Gregg Fonarow, coresearcher,  metformin improves myocardial function via activation of a signaling mechanism (AMP-activated protein kinase) independent of antihyperglycemic effects. Together, these studies suggest that metformin may be cardioprotective by augmenting heart function at the molecular level, and should be further investigated as a treatment for heart failure, irrespective of diabetes....

Ref : http://www.newsroom.ucla.edu/portal/ucla/ucla-study-demonstrates-that-metformin-150497.aspx