Tuesday, December 16, 2014

Another escalation in the fight against diabetes and obesity- A "Silver Bullet" in the making?

There are three hormones in human system that control the metabolism and absorption of glucose and they are now the focus of attention in developing appropriate therapy to attack the diabetes and obesity syndromes widely considered to be reaching epidemic proportions in many countries. These are glucagon, glucagon like peptide (GLP) and gastric inhibitory polypeptide (GIP) working in different ways in different locations in the body. In a remarkable breakthrough scientists have now achieved integration of these three hormones in a single molecule to derive all the benefits from them. While glucagon balances any hypoglycemia condition by releasing glucose from glycogen in the liver, GLP inhibits gastric secretion delaying carbohydrate absorption creating a satiety effect. GIP has a major role in neutralizing stomach acid besides slowing down transfer of food across the intestine. GIP also plays a role in insulin secretion enabling the body to metabolize glucose faster and its influence on lipid metabolism is recognized for its potential use against obesity. By combining these three hormones the researchers seem to have succeeded in creating a "silver bullet"  that can deal with both diabetes and obesity. Here is a gist of these findings which appears to be really path breaking in its impact.

"In 2012, we covered work led by Professor Richard DiMarchi that showed linking two hormones into a single molecule held promise as a treatment for obesity. DiMarchi followed this up last year by combining the properties of two endocrine hormones to provide an effective treatment for both obesity and adult-onset diabetes. Continuing in this vein, DiMarchi has now co-led a study whereby obesity and diabetes were effectively cured in lab animals by adding a third hormone to the molecular mix. Clinical work carried out last year, which included human clinical trials, showed a peptide combining the properties of two endocrine hormones, GLP-1 (glucagon-like peptide 1) and GIP (gastric inhibitory polypeptide), provided an effective treatment for adult-onset diabetes. Now the team, co-led by DiMarchi, the Indiana University (IU) Distinguished Professor of Chemistry, and Matthias Tschöp, director of the Institute for Diabetes and Obesity at the German Research Center for Environmental Health, has developed a new molecule that includes a third hormone, glucagon. GLP-1 and GIP are involved in enhancing insulin action and reducing blood glucose in the body, with GLP-1 also acting to reduce appetite. Meanwhile, glucagon is involved in improving liver function and increasing the long-term rate at which calories are burned. Molecularly combining these three hormones forms what is known as a triple agonist, which can bind to and activate receptors in the body and produce certain biological responses. "This peptide represents the first rationally designed, fully potent and balanced triple agonist ever achieved in the treatment of any disease," says DiMarch. "The benefits of the previously reported individual co-agonists have been integrated to a single molecule of triple action that provides unprecedented efficacy to lower body weight and control metabolism." The researchers say that in preclinical trials, this new peptide lowered blood sugar levels and reduced body fat better than all existing drugs. By triggering improved glucose sensitivity, reducing appetite and enhancing calorie burning, it was able to reduce body weight in rodents by around 30 percent, (nearly twice as much as the preceding GLP-1/GIP double hormone), and essentially cured the animals of obesity, diabetes and associated lipid abnormalities. "This triple hormone effect in a single molecule shows results never achieved before,"said co-first author Brian Finan, a scientist at the Helmholtz Diabetes Center. "A number of metabolic control centers are influenced simultaneously, namely in the pancreas, liver, fat depots and brain."

According to the innovators of this novel 3-in-1 hormone peptide molecule, extensive animal studies and limited clinical trials have more or less confirmed about its efficacy in increasing glucose sensitivity, reducing appetite significantly and enhancing burning of calories dramatically. Reduction of body weight to the extent of 30% is a remarkable achievement which will gladden the hearts of millions of people with BMI beyond 30. Hopefully this hormone combination will become the standard bearer in the coming years for world wide use in bringing down obesity, curing diabetes and correcting many lipid abnormalities for which there are no satisfactory treatment protocols at present. Though lot has been said about the efficiency and effectiveness of the new peptide molecule, nothing is mentioned as to how it is produced or how stable it is when administered in human beings. Since only GIP works at the intestinal level, how effectively the peptide is absorbed in the blood is also not clear. As human clinical trials have been carried out one can assume that the claims made by the innovators are valid. Whether there will be any other side reactions in some people is also not known. Let us hope we will have one of the most effective medicines to overcome the twin curses in the form of diabetes and obesity soon and association of one of the giants of pharma industry with this study further reinforces our hope.  


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