On an almost daily basis we read about Ozempic (semaglutide), which was licenced for diabetics, then Wegovy (also semaglutide), which was licenced for weight loss, and now Mounjaro (tirzepatide).
These drugs cause weight loss by increased insulin levels, appetite suppression, and burning fat. In addition to lifestyle improvements in sleep, diet and exercising, they will play a long-term role in the future of anti-ageing medicine. They may work in anti-ageing by improving mitochondrial function and reducing oxidative stress.
So, what is Semaglutide?
It is an analogue of GLP (glucagon like peptide)-1, which works at receptors in the pancreas, stomach, intestine and nervous system.
GLP-1 increases insulin. Insulin allows cells including muscle and liver to take up glucose and store it as glycogen. GLP-1 also inhibits the production of the antagonist hormone to insulin known as glucagon, which would otherwise cause glucose release into the bloodstream.
GLP-1 slows down gastric emptying, so you feel fuller for longer. This is probably the major source of the common side effects of nausea and constipation. GLP-1 also works centrally on the brain by telling the brain that we are full. This reduces hunger and appetite.
So, what is Tirzepatide?
This, in addition to working on GLP-1 receptors, works on GIP (glucose dependent insulinotropic polypeptide) receptors. These receptors are found in the pancreas, in fat cells and other areas of the nervous system.
Additional effects are due to the burning of fat known as lipolysis including in the central fat deposits like the liver.
It works at receptors for GLP-1 and GIP in the brain further enhancing appetite suppression.
It reduces cholesterol levels.
Side effects are much less common than Ozempic.
Ozempic/ Wegovy vs Mounjaro
Ozempic can result in weight loss of around 15% of your body weight in 12 months. Mounjaro can result in up to 25%. With increasing availability in the UK, it is superior at reducing blood sugar levels and reducing weight.
The inevitable dietary restriction and the need for exercise focusing on increasing muscle mass as opposed to cardiovascular exercise alone will best augment the metabolic effects associated with these hormonal mechanisms.
Benefits:
Reduce weight and all the complications of obesity. Calorie restriction has been shown to combat ageing.
Improve insulin sensitivity preventing and treating conditions like fatty liver, type 2 diabetes and polycystic ovarian syndrome (PCOS).
Tirzepatide has been independently shown in studies to reduce cholesterol levels.
Semaglutide has been shown to reduce heart attacks and strokes independent of its weight loss properties. This might be due to a direct effect on the blood vessels.
There is interesting documentation of reduction in addictive behaviour including drugs, alcohol and gambling.
Protecting the nervous system: GLP-1RAs can help protect the nervous system, which can help with age-related cognitive decline and neurodegenerative diseases. There is an ongoing study at Imperial University. London looking at the effects of GLP-1 Analogues in Parkinson’s Disease.
Anti-inflammatory properties.
Possible reduction in collagen breakdown implicated in ageing.
We can see these drugs being used long term at low doses (perhaps microdoses). I would like to aim, after initial weight loss, towards long term maintenance keeping weight stable, however maintaining all the beneficial listed above.
Risks:
Gastrointestinal – nausea and constipation. Very little with tirzepatide.
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