Obesity is much more than just extra kilograms; it’s a complex chronic disease that causes serious health problems worldwide. However, scientific breakthroughs have revolutionized this battle. New medications like semaglutide and tirzepatide have radically changed the approach to weight loss. These drugs not only reduce weight but also specifically target the body’s metabolism. As a result, patients achieve not only visual but also significant health improvements.
Semaglutide acts as a GLP-1-like agent, while tirzepatide stimulates both GLP-1 and GIP (glucose-dependent insulinotropic polypeptide) receptors. By mimicking these hormones, these drugs significantly reduce appetite, slow gastric emptying, and improve insulin sensitivity. Thanks to this mechanism, patients in clinical trials showed an average weight loss of 15% with semaglutide and up to 21% with tirzepatide.
Future Therapies:
Research is becoming more and more complex. Now, scientists are working on medications that act on multiple receptors simultaneously, changing the complex biological process of weight regulation. Two endogenous hormones, glucagon and amylin, are currently being researched. Both are naturally released when we eat and have a crucial role in metabolism.
Glucagon, released from the pancreas’s α-cells, acts on liver receptors. Its main function is to break down stored glycogen and fat. This process can significantly increase energy expenditure. Amylin, in turn, is released along with insulin from the pancreas’s β-cells. It helps control blood sugar levels by suppressing glucagon secretion, slowing gastric emptying, and enhancing the feeling of satiety, which is achieved by acting on brain receptors.
It is worth noting that pramlintide, an amylin analog, is already approved by the FDA and is actively used to treat diabetes. This medication, in combination with lifestyle changes, can lead to a 6-8% weight loss over one year.
New pharmacotherapies are designed to have a much longer-lasting effect, allowing the medication to be administered once a week or even once a month. These drugs simultaneously activate or suppress several hormone receptors, resulting in a maximal effect on weight loss and metabolic improvement. With this targeted action, side effects are also minimized.
Drugs currently in the research phase include:
- Cagrilintide – a long-acting dual agonist for amylin and calcitonin receptors. In combination with semaglutide, it showed an approximately 20% weight loss over 68 weeks.
- Survodutide – a dual GLP-1/glucagon receptor agonist that caused a nearly 15% weight loss in 46 weeks.
- Retatrutide – a triple GIP/GLP-1/glucagon receptor agonist. In 48 weeks, patients’ weight loss exceeded 24%. Both drugs are also being tested for the treatment of liver diseases associated with obesity.
- Maridebart cafraglutide – a monoclonal antibody that suppresses the GIP receptor and binds to GLP-1 analogs. With a once-a-month injection, it showed a 16% weight loss in one year. Its mechanism of action is still being studied.
Researchers are also actively working on creating oral medications, which will make treatment more convenient. At this stage, oral semaglutide (which is already used for diabetes) is being tested at higher doses against obesity. Also, orforglipron, a new non-peptide agent, showed a nearly 15% weight loss in Phase 2 trials.
In addition to hormones, scientists are also researching other mechanisms. One interesting direction is to influence the myostatin-activin receptor, which inhibits muscle growth. By suppressing this pathway, it is possible to increase muscle mass and reduce fat. Bimagrumab, an inhibitor of this pathway, was used with semaglutide and a 22% weight loss was recorded, almost entirely from fat.
These new approaches represent a serious change, as the focus is on combination therapies that act on multiple neuroendocrine pathways. Such a multi-faceted approach makes the weight loss process as effective as possible while also improving the patient’s metabolic and overall health.
Source: JAMA
