Type 2 diabetes is a major risk factor for cardiovascular disease related morbidity and mortality. With the development and progress of science and technology, the treatment of diabetes is no longer a three-legged situation of insulin, sulfonylureas and biguanides, but a variety of treatment methods have emerged. Among them, glucagon-like peptide-1 (GLP-1) receptor agonists are innovative treatments for type 2 diabetes.
GLP-1 agonists are a class of antidiabetic agents that mimic the actions of the glucagon-like peptide. GLP-1 is one of several naturally occurring incretin compounds that affect the body after they are released from the gut during digestion. By binding and activate GLP-1 receptors, GLP-1 agonists, and endogenous GLP-1 are capable to reduce blood glucose levels helping T2DM patients to reach a glycemic control. These antidiabetic agents increase the glucose-dependent secretion of insulin from functioning beta cells, decrease glucagon release after meals, decrease hepatic glucose production, delayed gastric emptying, suppress the appetite and promotes beta cell proliferation.
Actions of GLP-1 in target tissues. Image source: https://spectrum.diabetesjournals.org/content/30/3/202
A number of GLP-1 receptor agonists have become available in the United States since the approval of the first agent in the class in 2005, exenatide. These include the short-acting agents exenatide (Byetta) twice daily, lixisenatide (Adlyxin) once daily, oral semaglutide (Rybelsus) once daily, intermediate-acting liraglutide (administered once daily), and the long-acting agents administered once weekly, exenatide (Bydureon), albiglutide (Tanzeum), dulaglutide (Trulicity) and semaglutide (Ozempic). Among these GLP-1 agonist drugs, only semaglutide (Rybelsus) is taken orally, the others are injected under the skin. Properties of these agents are summarized in Table 1.
| Generic (Trade) Name | Developer | Dosing Frequency | Route of Administration | FDA Approval Year |
| Short-acting | ||||
| Exenatide (Byetta) | AstraZeneca | Twice daily | Injection | 2005 |
| Lixisenatide (Adlyxin) | Sanofi-Aventis | Once daily | Injection | 2016 |
| Oral Semaglutide (Rybelsus) | Novo Nordisk | Once daily | Oral | 2019 |
| Intermediate-acting | ||||
| Liraglutide (Victoza) | Novo Nordisk | Once daily | Injection | 2010 |
| Long-acting | ||||
| Exenatide (Bydureon) | AstraZeneca | Once weekly | Injection | 2012 |
| Albiglutide (Tanzeum) | GSK | Once weekly | Injection | 2014 |
| Dulaglutide (Trulicity) | Eli Lilly | Once weekly | Injection | 2014 |
| Semaglutide (Ozempic) | Novo Nordisk | Once weekly | Injection | 2017 |
Table 1: FDA Approved GLP-1 Agonist Drugs
GLP-1 agonist drugs are very effective in lowering blood sugar levels after meals and during fasting. Unlike some type 2 diabetes drugs, they are unlikely to cause low blood sugar (hypoglycemia).
They also do not cause weight gain. They may even contribute to weight loss, in the range of 1.5 to 3 kilograms. However, this amount varies depending on factors such as lifestyle or the use of other medications.
Although more research is needed, some GLP-1 agonist drugs have also been shown to be beneficial to the heart health and kidney function of diabetic patients.
For example, research has shown that treatment with Ozempic, Trulicity, Rybelsus, or Victoza is linked to significant reduction in major heart problems, such as heart attacks, in people with diabetes and existing heart disease.
Studies have also found that people who took certain GLP-1 RAs had better kidney outcomes than people who took a placebo.
The most common side effects are gastrointestinal. Nausea, vomiting, and diarrhea can occur in many people. Nausea may improve with time and a lower dose. Also, it may occur less often with the weekly types of medication.
Some reports link acute pancreatitis with GLP-1 agonists, but there are not enough data to establish a clear causal relationship.
| Pros | Cons |
| Relatively low risk of hypoglycemia | Delivered by injection * (once or twice daily, or weekly) |
| Strong efficacy/A1c reduction | Nausea/gastrointestinal side effects, generally decreasing over time |
| Weight loss (quite strong in some people) | More expensive than sulfonylureas/metformin |
| Other possible benefits (beta cell preservation, cardiovascular benefit) being investigated | Possibility of a slight association with pancreatitis (still being studied) |
Table 2: Benefits and Side Effects of Taking GLP-1 Agonist Drugs
Huateng Pharma is known worldwide for a variety of pharmaceutical intermediates used in research and development. Recognized for purity and quality, our products and brands are backed by technical and sales teams dedicated to providing you the best service possible. We can provide antidiabetic drugs intermediates such as liraglutide intermediates and semaglutide intermediates for your research. We can make scale-up production with capacities varying from gram to kilograms and multi tons.
Related Articles:
[1] Oral Peptide Therapeutics: Advances and Challenges
[2] Oral Semaglutide : First Oral GLP-1 Treatment for Type 2 Diabetes
[3] Liraglutide, Used For Treating Against Type 2 Diabetes And Obesity
[4] Antidiabetic Drugs Classification and Mechanism of Action
