Amazing breakthroughs for drugs treating obesity.
Blog Highlights:
- How do they work?
- Lose weight
- Prevent diabetes and reduce blood sugar
- Prevent fatty liver disease
- What are the new obesity drugs?
- How can Marin Biologic Laboratories help you with bioassays?
How do these drugs work, mechanism of action
- Help lower blood sugar
These new drugs tackle obesity and type 2 diabetes by stimulating insulin release (which promotes glucose uptake into cells for energy production), slowing down digestion, reducing appetite and reducing the release of glucagon (a hormone that increases blood sugar). With more insulin in the blood and less glucagon, blood sugar levels drop, which supports weight loss. The US has 28 million individuals suffering from diabetes, 12% of the population. The worldwide market for type 2 diabetes is ½ a billion people with a global market size estimated to be $60 bilion by 2030.
- Promote weight loss
Newer drugs (see below) have actions that lower blood sugar several ways, reducing the appetite and feelings of hunger, slowing the release of food from the stomach, and increasing feelings of fullness after eating. These drugs act as agonists (stimulate) to the glucagon-like peptide-1 (GLP-1) receptor and glucose-dependent insulinotropic polypeptide (GIP) to stimulate insulin secretion by the pancreatic islet cells. This decreases insulin resistance thereby increasing insulin sensitivity, and lowers hepatic lipid accumulation slows gastric emptying, decreases appetite, and reduces glucagon secretion. GLP-1 and GIP are hormones known as incretins.
Obesity is the leading cause of death in the US with 42% of the population positive for obesity. The global obesity market is predicted to reach $77 billion by 2030.
Drawbacks for weight-loss indication
Weight-loss drugs can offer significant benefits, but they also come with potential drawbacks and limitations:
- Side Effects: Many weight-loss medications can cause side effects, ranging from mild to severe. Common side effects might include nausea, diarrhea, constipation, headaches, dizziness, insomnia, and dry mouth. Some individuals may experience more serious side effects, such as increased heart rate, high blood pressure, or mood changes.
- Limited Long-Term Efficacy: While these medications can aid weight loss initially, their long-term effectiveness varies. Some people may experience weight regain after discontinuing the drug. Lifestyle changes, such as diet and exercise, are crucial for maintaining weight loss even after medication use.
- Not Suitable for Everyone: Weight-loss drugs are typically prescribed for individuals with a body mass index (BMI) above a certain threshold or those with obesity-related health conditions. They might not be suitable for everyone, and some medications have specific contraindications or are not recommended for certain health conditions or populations.
- Cost and Insurance Coverage: The cost of weight-loss medications can be a concern as they might not always be covered by insurance. Expenses associated with these drugs can be a barrier for some individuals.
- Limited Options and Individual Responses: Not all weight-loss drugs work the same way for everyone. Responses can vary, and there are limited options available, which might not address the diverse needs of individuals seeking to lose weight.
- Maintenance of Lifestyle Changes: Weight-loss drugs can provide a boost in the initial phase, but their effectiveness is enhanced when combined with lifestyle changes like diet modifications and regular exercise. Sustaining these changes can be challenging for some individuals.
- Potential Health Risks: Some weight-loss medications have been associated with potential health risks. For instance, certain drugs might affect the heart or have adverse interactions with other medications a person is taking.
New-generation GLP-1 receptor agonists:
The market for obesity and weight-loss drugs has increased dramatically. Several new obesity drugs are in various stages of development and approval. Some of the newer drugs include:
Ozempic and Wegovy are both medications developed by Novo Nordisk, belonging to the class of drugs called GLP-1 receptor agonists.
Ozempic (Semaglutide): It is a once-weekly injectable medication approved for the treatment of type 2 diabetes. Semaglutide, the active ingredient in Ozempic, works by mimicking the action of the natural hormone Glucagon-Like Peptide-1 (GLP-1). Ozempic has been shown in clinical trials to effectively lower blood sugar levels and also has the added benefit of promoting weight loss.
Wegovy (Semaglutide): Wegovy is a higher-dose formulation of semaglutide that was specifically developed and approved for chronic weight management in adults with obesity or who are overweight and have at least one weight-related condition. It’s also administered as a once-weekly injection and works similarly to Ozempic by reducing appetite and helping with weight loss.
Adults on average lost 35 pounds in a little over a year (68 weeks) for a 232 pound individual. No other obesity treatment has shown such dramatic effects for average people.
Second generation GLP-1 drugs
Mounjaro (Tirzepatide) is a novel investigational medication developed by Lilly. It belongs to a class of drugs known as dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonists. This medication has shown promise in clinical trials for the treatment of both type 2 diabetes and obesity.
Clinical studies have demonstrated that tirzepatide has potent glucose-lowering effects and also aids in weight management with its dual action on both the GIP and GLP-1 receptors. Tirzepatide is being investigated as a potential once-weekly injectable treatment for type 2 diabetes and as a potential treatment for obesity.
Tirzepatide may also be effective for treatment of Chronic Kidney Disease by targeting the underlying cause of the disease (Bueno et al., Clinical Kidney Journal, 15, pg
1593–1600). Chronic Kidney Disease affects more than 800 million people worldwide. Diseases and conditions that cause chronic kidney disease include:
- Type 1 or type 2 diabetes
- High blood pressure
- Glomerulonephritis, an inflammation of the kidney’s filtering units (glomeruli)…
Third generation GLP-1 drugs
Retatrutide (Lilly), the newest GLP-1 drug, works in three ways, it is considered a “tri-agonist.” Its direct targets are the receptors for Glucose-dependent Insulinotropic Polypeptide (GIP), glucagon-like peptide-1 (GLP-1) and glucagon.Like Wegovy, Mounjaro, and Ozempic, Retatrutide helps people lose weight and lower their blood sugar levels. However, Lilly’s clinical trials also demonstrated a powerful third outcome with Retatrutide. Results showed significant improvement in non-alcoholic fatty liver disease (NAFLD), a common and dangerous problem for people with obesity and metabolic syndrome.
Fatty Liver Disease
Non-alcoholic fatty liver disease (NAFLD) is a condition of fat, mostly triglycerides, accumulating in the liver, even in otherwise healthy-looking, thin individuals, causing injury to their liver cells. It affects about 30% of the US population.This increases the risk of progression to more serious conditions like fibrosis (scarring) of the liver, cirrhosis, and liver cancer. Non-Alcoholic Steatohepatitis (NASH), NAFLD with fibrosis, is the number one reason for liver transplant.
The new Lilly drug, Retatrutide, showed normal amounts of fat in NADLF patient’s liver after 2 years of treatment, effectively resolving their fatty liver disease in the short term. This remarkable effect is groundbreaking because 24% of Americans have NAFLD, and no FDA-approved treatments currently exist.
Surprisingly, to reduce liver fat, Retatrutide stimulates the production of glucagon. As noted above, glucagon increases glucose, but it also helps eliminate fat in the liver. At first, this kick in glucagon levels sounds counterproductive. Scientists have yet to understand why fully, but when combined with its two other mechanisms, Retatrutide lowers blood sugar levels and excess fatty acids in the liver.
Marin Biologic Laboratories can help you
Marin Biologic can assay your GLP-1 drug candidate in a quantitative potency bioassay. The reporter assay measures cAMP generated by engagement of the GLP-1 receptor by an agonist. An alternative method is the production of luminescence from a luciferase reporter cell line. The method is a very precise assay with one day turn around. Validated GMP assays are available.
Marin Biologic Laboratories provides solutions in protein/gene analytical and biological assays and other services for our many clients, with or without GLP/GMP conditions. Marin Biologic develops, validates, and performs a variety of assays for
- GMP potency assay for lot release, GLP assays
- ELISA, PK and PD studies, immunogenicity (Anti-Drug Antibodies), neutralizing antibodies
- Humoral and cellular immunity assays.
- Cell-based assays, proliferation and toxicity assays
- Molecular, Biochemical and Biology services, protein production, purification, enzyme assays, cloning, transfections
- Radioactive procedures and analysis.
Marin Biologic Laboratories is a contract laboratory for pharmaceutical and biotech industries. We have been operating for over 27 years and we take pride in our science as well as the quality of our communication. We specialize in the development and validation of a wide range of cell-based assays, including cell-based potency assays and lot release assays, for diverse drug platforms such as small molecules, immunotherapy, gene therapy, and antibody drug conjugates (ADC). Additionally, we perform assays for drug transport using virus/plasmid, nanoparticles, liposomes, small and large molecules (proteins and DNA/RNA. Our expertise encompasses ELISA, radioimmunoassay (RIA), enzyme assays, protein and RNA expression analyses, protein/monoclonal antibody purification, viral transduction and expression analyses, transfection, and radioactivity methods, including radionuclide assays for radiopharmaceuticals.
We successfully passed a FDA inspection for a commercial drug. We would like to help meet your requirements in a timely and cost-effective way. Do you need to send us your confidentiality agreement or we can send a template to you?
We have developed and performed a variety of human and murine cellular immunology assays ex vivo, macrophage/monocyte activation, lymphocyte proliferation and cytokine production and cell surface markers (FACS analysis), NK, ADCC, cytotoxic T lymphocyte (CTL), complement killing, etc. Our niche is to take projects encompassing several fields such as biochemistry, molecular and cell biology and bring them to a rapid and successful conclusion.
