A new era of weight loss pharmaceuticals called incretin mimetics could drastically change the trajectory of obesity across the world. Glucagon-like peptide 1 (GLP-1) receptor agonists or GLP-1 analogues mimic incretin hormones that the body naturally produces to stimulate the release of insulin and lower blood sugar levels. According to the National Institute of Health, 1 in 3 adults (30.7%) are overweight, and more than 2 in 5 adults (42.4%) have obesity, with severe obesity doubling in the last decade, affecting nearly 10% of the US population. Obesity has skyrocketed and this new age of biopharma, could help solve the problem.
Diabetes drugs, like dulaglutide (Trulicity), liraglutide (Victoza), and semaglutide (Ozempic), have gained increasing popularity showing remarkable results not just in the treatment of Diabetes, but also in the treatment of obesity. We’re going to talk more about GLP-1 for weight loss, the benefits, and how it works.
The concept and discovery of incretin in the treatment of diabetes, was discovered more than a century ago, by scientists Bayliss and Starling, in 1902. They hypothesized that gut extracts contain a hormone that regulates the endocrine pancreas and showed that administration of gut extracts reduces the amount of urine sugars in patients with diabetes, presumably through stimulation of the endocrine pancreas. In 1929, glucose lowering extracts, were purified, and named incretin,
Two hormones, gastric inhibitory polypeptide (GIP) and glucagon‐like peptide‐1 (GLP‐1), have been shown to act as incretins.
GLP‐1, a 31‐amino‐acid hormone produced from proglucagon and secreted from L cells of the lower intestine and colon, directly acts on pancreas cells called islets and stimulates insulin secretion in isolated islets (R). GIP is a 42‐amino‐acid hormone secreted from K cells of the upper small intestine and found to stimulate insulin secretion and inhibit gastric acid secretion.
GLP-1 is an incretin hormone. It is secreted from the intestine on ingestion of glucose or nutrients to stimulate insulin secretion from pancreatic beta cells. Incretin mimetics are agonists; they mimic these hormones, made by the gut and brain. They target hunger hormones like leptin and ghrelin, effect insulin sensitivity, and slow down gastric emptying (R).
Activation of the glucagon-like peptide 1 (GLP-1) receptor has been shown to decrease glucose, reduce appetite, lower body weight, and improve insulin sensitivity in patients with type 2 diabetes and obesity.
GLP-1 stimulates insulin secretion (which then allows cells to take up glucose) and inhibits glucagon secretion (which prevents more glucose from going into the bloodstream) to lower blood sugar levels. GLP-1 also slows stomach emptying, meaning that less glucose from food is released into the bloodstream.
Type 2 diabetes is the most common form of diabetes. It occurs when the pancreas cannot make enough insulin to keep blood sugar at normal levels, causing patients to be hyperglycemic. GLP-1, an endogenous hormone, is often found in insufficient levels in type 2 diabetes patients, who are often over weight.
GLP-1’s helps the pancreas release the optimal amount of insulin, which transports glucose (sugar) to tissues in the body where it can be used for energy. GLP-1 are very effective at lowering blood sugar levels and have been found to suppress appetite and induce substantial weight loss.
Currently, Semaglutide, a GLP-1 receptor agonist has been approved by the U.S. Food and Drug Administration and is currently marketed in various dosage strengths and forms as Ozempic®, Rybelsus®, and Wegovy®. Ozempic is indicated to treat type II diabetes, and Wegovy the same drug, is indicated for weight loss and obesity.
Other GLP-1’s drugs in the incretin mimetic class and approved for diabetes and lowering hemoglobin A1C levels, include Trulicity (dulaglutide). exenatide (Byetta, Bydureon), liraglutide (Victoza), sitagliptin (Januvia, Janumet, Janumet XR, Juvisync), saxagliptin (Onglyza, Kombiglyze XR), alogliptin (Nesina, Kazano, Oseni), and linagliptin (Tradjenta, Jentadueto).
More recently, research efforts have explored the potential co-activation of the glucose-dependent insulinotropic peptide (GIP) receptor as a means of enhancing the therapeutic benefits of GLP-1 receptor activation. Tirzepatide is a dual GLP-1/GIP receptor agonist that is approved by the U.S. Food and Drug Administration and is currently marketed as Mounjaro (R).
Studies have shown that GLP-1s and dual agonists pharmaceuticals, using GLP-1 and GIP, can induce up to 20lbs of weight loss in only 30 days.
In a double-blind, randomized controlled trial, published in the New England Journal Of Medicine 1961 obese adults, who did not have diabetes, were randomly assigned to 68 weeks of treatment with once-weekly subcutaneous semaglutide (at a dose of 2.4 mg) or placebo, plus lifestyle intervention. The coprimary end points were the percentage change in body weight and weight reduction of at least 5%. The mean change in body weight from baseline to week 68 was −14.9% in the semaglutide group as compared with −2.4% with placebo, which is up to 30lbs.
Other new novel GLP-1 agonists, such as VK2735 in Phase 2 clinical trials, has shown subjects to lose up to 18lbs in just 28 days.
Although GLP-1 receptor agonists, are indicated to treat diabetes, new indications for these drugs, such as Wegovy have recently been approved for obesity and weight loss. The current issue, is that they are very expensive. None the less, incretin mimetics will lead the new era of biopharmaceutical drugs, for weight loss. Evidence shows, that GLP-1 and incretin mimetics, can produce significant positive effect on blood sugar, appetite, and gastric emptying. These benefits combined, can help other chronic disease or metabolic disease states, such as cardiovascular disease and obesity.
Of course, diet and exercise, is also vastly important for sustained weight loss and and overall health and well-being. Weight loss to a achieve manageable weight is just part of the journey.
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