Dr Joseph K. Joseph
Ahead of her daughter’s wedding, a woman in Australia took semaglutide to lose weight. She lost her life. The drug became widely popular on social media after billionaire entrepreneur Elon Musk posted about how he lost around 10kg after using the molecule. The drug, which belongs to a class of medications called glucagon-like peptide-1 (GLP-1) agonists, works by sending signals to the brain that you have achieved satiety even if you actually have not.
GLP-1 is a hormone that is produced in the small intestine. It stimulates insulin secretion (which allows cells to take up glucose) and inhibits glucagon secretion (which prevents more glucose from going to the bloodstream) to lower blood sugar levels. GLP-1 also slows stomach emptying, meaning less glucose from food is released into the bloodstream. GLP-1 increases satiety after eating, which contributes to its weight loss property. Most GLP-1 are taken by injection. The exception is rybelsus, which is the world's only oral GLP-1 pill. Common side effects are nausea, vomiting and diarrhoea.
But how did the woman die? The drug caused a rare complication called ileus, which is paralysis of the intestine. This caused waste to accumulate in her body by curbing her defecation and urination processes. And she took the drug mainly for weight loss, not for diabetes that was the original indication. If she was diabetic, perhaps this side effect would not have occurred.
So, clinicians and patients must be careful when using GLP-1 agonists for the first time. If a patient is diabetic with a body mass index of more than 30, there is no harm in trying the drug. But for a non-diabetic patient with a BMI of less than 28, I would not recommend it straightaway.
GLP-1 agonists were not developed as weight loss drugs. They were developed to overcome insulin resistance by suppressing the appetite, whereby they reduce post prandial sugars. Patients who were injecting 100 units of insulin can reduce their insulin dose by more than 50 per cent when GLP-1 is used concomitantly for at least two months. So, for diabetes, this is a wonder drug. All diabetologists prefer lower insulin intake in obese patients as insulin causes weight gain. Patient using GLP-1 would lose more than 7kg in two months―weight loss that overcomes insulin resistance.
At present, research is ongoing to see if GLP-1 can reverse (NASH) non-alcoholic steatohepatitis if used in early stages. The initial data seems encouraging. However, in late stages, the effect may not be that promising. So, the key is: when fatty liver is first detected and the BMI is above 30, with impaired fasting glucose values, GLP-1 may be used. If we actually reverse NASH, the progression to cirrhosis maybe prevented.
In spite of this, if you ask me if the craze for weight loss drugs is justified, the answer is no. Because an individual must always try to maintain optimum weight through healthy eating and exercise. Only if it fails must external molecules like GLP-1 be used and that too if it is medically indicated. Because each allopathic molecule has its side effects as we saw in the case above.
Still, GLP-1 agonists remain the most promising anti-obesity drugs approved by FDA till date, and, if early trial results are anything to go by, the management of diabetes and obesity is set to undergo a paradigm shift in the coming months as weight reduction can reduce risk of hypertension and cardiovascular diseases in a big way.
Joseph is specialist, internal medicine and diabetology, Zulekha hospitals, Dubai.