OBESITY IS A WORLDWIDE EPIDEMIC
30% Obesity Rate Worldwide
According to a report from the 2014 McKinsey Global Institute, more than 2.1 billion people – approximately 30% of the world population – are classified as overweight or obese by the World Health Organization. The trend is unprecedented, never seen before in history. Projections show the prevalence of obesity increasing to roughly 50% of the world’s population by 2030 with the current trajectory. 5% of all deaths annually are said to be obesity-related, and it is estimated to have cost the global economy $2.0 trillion in 2012, or 2.8% of the global GDP, based on direct costs (i.e., healthcare) and indirect costs (i.e., lost productivity). Obesity costs the US economy almost $700 billion annually.
The Health Risks Associated with Obesity
Being overweight or obese is not merely a cosmetic problem. The risks of developing the following health problems are greatly increased by being overweight or obese:
– Coronary heart disease including angina, heart attack, and heart failure.
– High blood pressure.
– Type 2 diabetes, which itself is a leading cause of early death, coronary heart disease, stroke, kidney disease, and blindness.
– Abnormal blood fats including high levels of triglycerides and low density lipoprotein (“bad cholesterol”) and low levels of high density lipoprotein (“good cholesterol”), which increase the risk of coronary heart disease.
– Cancer, in particular colon, breast, endometrial, and ovarian.
– Sleep apnea.
– Reproductive problems.
– Gastroesophageal Reflux Disease.
Current Drug Treatments are not Optimal
Almost all marketable drugs used to treat obesity today are appetite suppressants, which work by acting on the brain’s satiety center. However, this action can lead to depression (including suicidal thoughts) due to close proximity of satiety centers to the brain’s pleasure centers. Other drugs (e.g., exanatide and liraglutide) can also delay emptying of the stomach to create a false sense of fullness, although frequently this sensation comes at the expenses of producing nausea and vomiting. In fact, recent clinical studies have reported that the weight loss produced by these drugs is directly proportional to the delay in stomach emptying. Thus, while these drugs do work well in a laboratory or clinical research setting, when used as therapy, they often lead to a great deal of discomfort in the process due to the undesirable side effects.
Insulin is the Answer
Insulin is known as an “efficiency hormone.” It is the most potent hormone known to promote the synthesis and storage of carbohydrates and lipids, while inhibiting their breakdown. Insulin is thus not only an instrumental component in maximizing energy storage and survival, but also a key factor in the development of obesity and related diseases. Historically, food was scarce, and all organisms needed to adapt in order to obtain and store as much nutrients when they were available in order to survive, a role that was provided by insulin. However, life today is different as food is now plentiful, and our diets have changed. Finally, we lead more sedentary lifestyles, and consequently the necessity to efficiently break down and store as much food as possible is not as pronounced.
A landmark human study published in 1964 in The Lancet observed the effects of oral and intravenous (IV) glucose on plasma insulin and glucose. It showed that insulin release was decreased by nearly ⅔ when IV glucose was given to humans compared to oral glucose. However, blood glucose levels were found to be similar, and something in the intestine was thus felt to be responsible for this observation. The responsible agents, which at that time were unidentified, are now known to be incretin hormones, which promote insulin release.
GIP is an Incretin Hormone
Gastric inhibitory polypeptide (GIP) is a hormone found in the upper small intestine, which is released into blood by lipids and carbohydrates. Its precise role was initially unclear but was felt to be the suppression of acid secretion (hence its name). Later, with his development of a GIP peptide antagonist, Dr. M. Michael Wolfe, Chief Medical Officer of Lobesity, proved that GIP was also a potent incretin hormone. He found that this antagonist decreased insulin levels by ⅔, with little effect on glucose levels, thereby providing an account for the unexplained observations seen in the 1964 Lancet study.
Many further studies were performed to better understand GIP. A summary of the results reveals that over-nutrition increases GIP release, which leads to higher glucose absorption from the intestine coupled with greater insulin release. These changes result in increased glucose uptake into fat cells and subsequently conversion into fat stores. With the GIP peptide antagonist, however, intestinal glucose absorption is decreased, and insulin release is diminished. The antagonist also reduces glucose uptake into fat cells and conversion into fat. Ultimately, these effects result in weight loss and the prevention of weight gain.
Putting it all Together
Lobesity has developed a humanized monoclonal antibody (mAb) that binds specifically to GIP (anti-GIP mAb). The anti-GIP mAb does not affect appetite at all, but rather, it blocks obesity at its roots, producing less efficient eaters by decreasing both nutrient absorption from the intestine and nutrient storage. It is designed to prevent GIP from binding to its receptor, therefore decreasing GIP activity, similar to the effect of the GIP peptide antagonist. Due to the nature of monoclonal antibodies, it is long-acting and highly specific, making it a very safe and practical method for commercial development to effectively and safely treat obesity.
Currently, the anti-GIP mAb is being prepared for human clinical testing. Early results in mouse models have already shown great promise. In an obesity prevention study where mice were fed a high fat/high carbohydrate diet, anti-GIP mAb treatment resulted in a dramatic 46.5% decrease in weight gain (similar to a control diet group) versus mice that were not treated. MRI scans and subsequent dissection of these mice also revealed a large reduction in abdominal cavity and liver fat. Furthermore, untreated mice developed type 2 diabetes, while those that were treated did not. These important findings indicate a further protective effect of our anti-GIP mAb against obesity and related diseases. Finally, the antibody has been shown to reverse obesity. Once developed, Lobesity’s anti-GIP mAb will become a revolutionary method for treating one of the world’s most pressing problems — the obesity epidemic.