Overview of GLP-1 Weight-Loss Drugs
Danish pharmaceutical company Novo Nordisk has introduced the weight-loss injectable semaglutide, following Eli Lilly’s tirzepatide in India. These GLP-1 therapies have been effective in helping individuals lose 15% to 20% of body weight, comparable to bariatric surgery outcomes. They are also beneficial for cardiovascular diseases, kidney disease, non-alcoholic fatty liver disease, and obstructive sleep apnea.
Mechanism of GLP-1 Drugs
- GLP-1 Receptor Agonists: Semaglutide and tirzepatide belong to this class and mimic gut hormones incretins, aiding in type-2 diabetes and obesity management.
- Functions:
- Enhance insulin secretion for better glucose utilization.
- Inhibit glucagon, reducing glucose release from the liver.
- Slow gastric emptying to prevent blood glucose spikes.
- Suppress appetite by signaling fullness to the brain.
- Additional Action: Tirzepatide also mimics the action of glucose-dependent insulinotropic polypeptide (GIP).
Discovery and Development
- Historical Context: Interest in incretins re-emerged in the 1960s, leading to the discovery of GLP-1 in 1986.
- Trials and Challenges:
- GLP-1 infusions increased insulin but were unstable.
- Novo Nordisk developed liraglutide but faced nausea issues, mitigated by dose adjustments.
- Semaglutide, a weekly injectable, showed higher effectiveness, leading to obesity management approval in 2021.
Clinical Benefits and Studies
- Weight Loss: Semaglutide users lost an average of 15% body weight, while tirzepatide users lost up to 20%.
- Cardiovascular Benefits: Semaglutide reduces major cardiovascular events by 20% and all-cause mortality by 19%.
- Liver and Other Health Benefits:
- Resolves fatty liver in 63% and improves liver fibrosis in 37% of cases.
- Tirzepatide shows efficacy in treating obesity-related obstructive sleep apnea.
- Neurological and Addiction Impact: Potential in reducing Alzheimer’s risk and aiding in addiction recovery.
Future Developments
The success of these drugs has spurred development of new drugs, including monthly dosages and effective oral pills. Trials for retatrutide, CagriSema, and Survodutide are ongoing, expanding treatment options.