New Delhi: It’s emerged as the new ‘wonder drug’ that promises to treat difficult diseases like diabetes and obesity. And now it seems the ‘miracle drug’ semaglutide may have another game-changing side effect: curbing alcohol cravings.
The top health institute in the United States, the National Institute of Health, is set to start randomised clinical trials to study whether semaglutide can curb alcohol cravings in addicts, following favourable results from laboratory experiments.
The results from these human studies may be several months away but if they are also favourable, it will be another remarkable addition to the long list of medical conditions the ‘wonder drug’ can treat.
But, while high costs have meant that many cannot afford the drug, endocronologists also say that safety of the drug in the long term still remains to be assessed. Also, there are some concerns on how the drug works in case of other diseases in non-diabetic patients and how long the effects last after stopping the medication.
Several studies so far have established that GLP-1 drugs—a class of drugs to which semaglutide belongs—can reduce the risk of strokes and heart attacks for people with cardiovascular disease or chronic kidney disorders, ease sleep apnoea symptoms, and even slow the progression of Parkinson’s disease.
That is not all. GLP-1 drugs—originally approved to treat diabetes—have also shown significant benefits even for those suffering from fatty liver and HIV complications, apart from age-related dementia and cognitive dysfunction.
“GLP-1RA as a pharmacotherapy seems to be a polypill since it causes a lot of remission in obesity and adiposopathy-driven chronic disorders. And there is now evidence to show it can also reduce the urge to drink alcohol and may be helpful in alcohol de-addiction,” Mumbai-based diabetologist Dr Rajeev Kovil told ThePrint.
Two GLP-1 drugs mimicking a natural gut hormone known to send signals of a full stomach to the brain, that have made waves across the world over the last few years, include another weight-loss drug tirzepatide apart from semaglutide.
“These drugs have created the biggest buzz in the pharmaceutical industry and have been phenomenally successful as evidence is mounting that apart from diabetes—a massive global health burden for which they were initially intended—they can be used to manage a host of other conditions,” said a senior pharmacologist associated with Delhi’s Maulana Azad Medical College.
“The strike rate that this class of drug is showing is mind-boggling,” the pharmacologist, also attached to various committees of Central Drugs and Standard Control Organisation, told ThePrint.
Also Read: This experimental lung cancer drug outperforms blockbuster medicine Keytruda. But there’s a catch
Growing popularity
For thousands of people who have struggled with weight and other associated problems, GLP-1 drugs are a ‘miracle’ cure. They have created a buzz with several celebrities speaking out openly about taking weight-loss medications.
In the United States, semaglutide is sold under Danish drug maker Novo Nordisk brands Ozempic for diabetes and Wegovy for obesity. U.S.-based pharma giant Eli Lilly’s tirzepatide, on the other hand, is available under the brand names Mounjaro for diabetes and Zepbound for obesity.
One reason for their popularity is that these injections have to be administered weekly, doing away with the daily dose needed with other drugs.
In India, however, semaglutide is only available in oral form under the brand name Rybelsus for application in adults with diabetes mellitus or type 2 diabetes.
The weekly injectable semaglutide as well as tirzepatide–though approved by the country’s apex drug regulator–are yet to be launched, mainly due to supply issues.
How it works
But how do these drugs work? Quite simply, these drugs target receptors in the brain that reduce the appetite and help people eat smaller meals and feel fuller for longer.
According to Kovil, these drugs reduce cravings by working on the brain and leaving users full with smaller portions.
Kovil added that they are even safe for people with diabetes as they also stimulate insulin only in the presence of glucose.
The main feature of obesity drugs is that they mimic the natural GLP-1 hormone–which controls blood sugar–and activate the same receptors that it would typically target.
But as synthetic drugs are long-lived, their effects extend well beyond those of the hormone they copy.
The body has two natural GLP-1 systems: one in the intestine and another in the brain.
After each meal, cells in the gut lining produce GLP-1. This, in turn, triggers the pancreas to release insulin, which helps to regulate blood sugar levels, suppress the appetite and slow down digestion.
The second system, on the other hand, gets activated only under certain conditions, such as after a large meal or in response to a stressor such as an infection.
In these cases, neurons in the lower back region of the brain called the hindbrain-including part of the brainstem-can also produce GLP-1, and there are receptors for the hormone in many neurons across the brain. They include those involved in appetite control, mood regulation, reward, and movement.
These systems appear to be entirely separate. It was once thought that gut GLP-1 communicates with hindbrain neurons by signaling through the vagus nerve, which goes up through the brainstem. There is evidence to suggest that these systems don’t normally interact.
The gut hormone is quickly metabolised after it is released into the bloodstream: it disappears in only a few minutes.
Synthetic GLP-1 drugs, however, last much longer in the body–a week or more–and that is a key reason why they are better at getting into the brain.
“These drugs target GLP-1 receptors, which are typically activated by the gut hormone GLP-1. By acting on these receptors, they trigger several physiological changes. The primary mechanisms include stimulating insulin release after meals, reducing appetite, and slowing stomach emptying, which promotes a feeling of fullness and curbs food cravings,” said Dr Rajeev Jayadevan, a clinician and researcher based in Kerala.
Beyond diabetes & obesity
Weight-loss drugs could have a big market in India where experts say more than 100 million people struggle with obesity.
Kovil says obesity is the “mother of a large number of non-communicable diseases”.
There is enough evidence to suggest, he says, that the wrong deposition of fat in the organs drives the epidemic of diabetes, several types of cancers, heart-related ailments, metabolic dysfunction-associated steatotic liver disease (MASLD) and obstructive sleep apnea, among others.
“The brain is the kingpin in metabolic blunders like diabetes and obesity and the liver seems to be the first deputy to the brain in this crosstalk which occurs between many organs,” Kovil said.
“So the treatment also cannot be fractured, and GLP1-RA drugs have a direct impact on the core problem–rather than the effects, to put it in simple terms–and have, therefore, emerged as the most advanced therapeutic to address a number of obesity-linked ailments.”
Results from long-term trials show they are effective in reducing the incidence of death, heart disease and strokes in people with diabetes and also those with obesity without diabetes.
In addition, the drugs have also been shown to cause remission of sleep apnea and non-alcoholic fatty liver disease, apart from offering significant improvement in Alzheimer’s disease–often referred to as type 3 diabetes as it is linked with the impact of insulin resistance on the brain.
According to Dr Anoop Misra, endocrinologist and chairman of Fortis C-DOC Hospital for Diabetes and Allied Sciences in Delhi, this class of drug has neuroprotective and anti-inflammatory effects that may slow cognitive decline in Alzheimer’s disease.
In addition, these drugs can improve cardiovascular health, potentially reducing risk factors associated with dementia and other conditions, Misra underlined.
A recent study published in the New England Journal of Medicine found that injectable semaglutide reduced death rates over a three-year period in obese and overweight people with cardiovascular disease without diabetes.
While the exact mechanism behind this benefit remains unclear, semaglutide may act through additional pathways beyond GLP-1 activation, such as reducing inflammation.
Ongoing research is exploring other potential mechanisms by which these drugs could have generated these effects, said Jayadevan.
However, experts also warn about the side effects of GLP-1 drugs.
Nausea, bloating, vomiting and diarrhoea are known side effects of these medicines and in rare cases, they can also cause stomach paralysis, a disorder that affects the normal movement of the stomach muscles.
(Edited by Sugita Katyal)