Rates of type 2 diabetes are on a rapid global upswing, necessitating more effective treatment methods. GLP-1 agonists, designed to regulate blood glucose levels and curb appetite in Type 2 diabetes patients, have been a significant advancement. However, their swift degradation in the body mandates frequent administration, either in the form of oral tablets or injections.
A pioneering study conducted by researchers at the University of Tabriz, Iran, has successfully fused native GLP-1 with another protein, substantially extending the compound's half-life. This breakthrough may represent a crucial step towards developing a longer-acting and more efficient treatment for Type 2 diabetes.
Published in Nature Scientific Reports, this study addresses a pressing issue. With diabetes affecting a staggering 529 million individuals worldwide, estimates suggest this number could more than double to 1.31 billion by 2050. The two primary diabetes types, Type 1 and Type 2, have distinct origins. Type 1 diabetes arises when the pancreas ceases to produce insulin, the hormone that regulates blood sugar. On the other hand, Type 2 diabetes emerges when the body becomes less responsive to the insulin produced by the pancreas.
Alarmingly, over 90% of diabetes cases are attributed to Type 2. Factors such as being overweight or obese, leading a sedentary lifestyle, family history, and advancing age contribute to the heightened risk of Type 2 diabetes. Worryingly, the prevalence of this condition is increasing among younger individuals.
Treatment options for Type 2 diabetes include lifestyle modifications such as diet and exercise, alongside medications like metformin, insulin, and GLP-1 receptor agonists, more commonly known as GLP-1 agonists. These drugs work by reducing blood glucose levels, slowing down stomach emptying, and stimulating insulin secretion. Nevertheless, they have a notable drawback - their limited half-life, necessitating either daily injections or the daily or weekly intake of tablets.
Existing GLP-1 receptor agonists are available in two forms: short-acting, which require twice-daily injections, and longer-acting, which necessitate daily or weekly injections. The short-acting exenatide, for example, primarily affects post-meal blood glucose levels and gastric emptying, with limited impact on fasting blood glucose. Longer-acting versions like liraglutide, semaglutide, and dulaglutide focus on reducing fasting blood glucose levels and regulating insulin and glucagon secretion.
This groundbreaking study seeks to overcome the issue of short half-life by creating chimeric proteins, uniting GLP-1 with a human serum albumin (HSA)-binding DARPin. Computational analysis has indicated that these engineered proteins maintain their biological activity and the capacity to bind to target proteins. Should the results of clinical trials prove successful, the "mGLP1-DARPin-1" fusion protein, resistant to DPP-IV cleavage, could be administered as a long-lasting injectable form of GLP-1. Similarly, the "mGLP1-DARPin-2" fusion protein, resilient to both DPP-IV and trypsin cleavage, has the potential for oral delivery via bioencapsulation in plant cells.
Though this computational study is promising, further research remains crucial. Dr. Pouya Shafipour, a board-certified family and obesity medicine physician, suggests that the new approach may lead to a more sustained increase in GLP-1 levels, potentially offering a significant advantage over current GLP-1 receptor agonists.
Existing GLP-1 agonists have known side effects, including nausea, vomiting, diarrhea, skin reactions at injection sites, and a possible risk of acute pancreatitis. These side effects may intensify with longer-lasting treatments. However, the new technology might mitigate these side effects, presenting a potential advantage.
In conclusion, while the study offers a promising avenue for the treatment of Type 2 diabetes, challenges such as immunogenicity, cost, and administration methods must be addressed. Only further experimental validation and clinical trials can confirm the safety and efficacy of these fusion proteins.
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