New Delhi: Dr Ambrish Mithal, chairman and head, endocrinology and diabetes at Max Super Speciality hospital in Delhi, has been fielding anxious queries from a number of his patients over the past few days, some of whom are almost panicked.
They are wondering if they should stop taking Rybelsus — the brand name of the ‘blockbuster’ diabetes medicine semaglutide made by the Danish drug company Novo Nordisk, which is available in India.
Their anxiety was triggered by a CNN report, which featured some women who developed gastroparesis or stomach paralysis — a disorder that affects the normal movement of the stomach muscles — after using semaglutide for several years.
The report added that some of the women, who are still suffering from the condition even months after quitting the treatment, have even contacted the US Food and Drug Administration.
“Till some time back, my phone was buzzing with requests for prescriptions for semaglutide, but there is a sense of panic now,” Mithal told ThePrint.
Semaglutide is sold under the names Ozempic (for diabetics) and Wegovy (for obese people with or without diabetes) in the US and other countries as injections.
The version of the drug approved in India, Rybelsus, is a pill — not a shot like Ozempic and Wegovy — and has lower doses. Therefore, it is less potent, the doctors ThePrint spoke to said, adding that it does help diabetics lose weight significantly.
Some rich patients who can afford it, however, do get the injectable semaglutide imported to India, the doctors said. An Ozempic injection costs about Rs 20,000, while a strip of 10 Rybelsus tablets costs nearly Rs 3,000 in India.
Mithal’s advice to his patients is as follows: Strong weight loss drugs like semaglutide and its predecessor liraglutide do have some side effects, but they may not have to stop the medication if they are tolerating it well.
“Also, while some patients cannot tolerate the medication and are then taken off the medication, so far, in my practice, I have not seen anyone suffering from serious adverse events such as stomach paralysis,” he added.
Echoing him, Dr Praveen Kumar P, a diabetes specialist based in Kochi, also said that while some stomach problems — such as nausea, vomiting and bloating among others — are known side effects of the type of drugs that semaglutide belongs to, he has not seen any patients with gastroparesis.
With the issue raising concerns in the US, Novo Nordisk in a statement to ThePrint said, “Semaglutide has been thoroughly tested in robust clinical development programmes, large real-world evidence studies and has cumulatively over 9.5 million patient-years of exposure.”
According to the drugmaker, gastroparesis is a clinical syndrome characterised by delayed gastric emptying — the process by which the contents of the stomach are moved into the duodenum — in the absence of mechanical obstruction of the stomach. “While diabetes is a well-known risk factor, there are other risk factors that may increase the risk of gastroparesis, such as overweight/obesity, gender (female), virus infection and nervous systems disease, such as Parkinson’s disease or multiple sclerosis,” the statement said.
“Patient safety is of utmost importance to Novo Nordisk. We recommend patients take these medications for their approved indications and under the supervision of a healthcare professional. We are continuously monitoring the safety profile of our products and collaborate closely with authorities to ensure patient safety, including adequate information on gastrointestinal side effects in the label,” it added.
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Semaglutide and its side-effects
Semaglutide and liraglutide, and before them exenatide and dulaglutide, are a group of medicines used for type 2 diabetes, and sometimes for obesity. They work by attaching to receptors of gut hormones such as glucagon-like peptide-1 (GLP-1).
“These receptors control the release of pancreatic hormones, appetite and gut function,” said Dr Rajeev Jayadevan, a gastroenterologist and medical researcher from Kerala.
Natural hormones made by the intestine like GLP-1 stimulate insulin secretion after a meal. Artificial GLP-1 agonists, such as semaglutide, have thus been used in diabetic patients to improve insulin release, he explained.
“Another effect of these drugs is delayed gastric emptying due to reduced intestinal movement. This gives a feeling of fullness in the stomach, which also helps with losing weight, besides better control of blood sugar,” Jayadevan explained.
However, nausea, bloating, vomiting and diarrhoea are known side effects of this class of medicines, he said, adding, “The drugs have been around for nearly 18 years, and these are listed on the drug labels.”
According to Mithal, while most patients experience these side effects for two-four weeks once they are started on the medication, these symptoms usually settle with anti-nausea medication.
“But if some patients complain of side-effects despite symptomatic treatment or have prolonged problems, we ask them to get off these new-age diabetic medications,” he added.
According to Dr Anoop Misra, chairman of Delhi’s Fortis-C-DOC Centre of Excellence for diabetes, metabolic diseases, and endocrinology, these drugs may worsen intestinal function and cause vomiting in a small number of diabetes patients with poor intestinal activity, especially those with long-term diabetes.
“Fortunately, the majority of patients won’t encounter such side effects, making it a relatively safe option for weight reduction,” he underlined.
Meanwhile, in its statement to ThePrint, Novo Nordisk pointed out that GLP-1 has been used to treat type 2 diabetes for more than 15 years, and to treat of obesity for eight years. Novo Nordisk GLP-1 products, such as semaglutide and liraglutide, have been in the market for more than 10 years.
For semaglutide, most gastrointestinal side-effects are mild to moderate in severity and of short duration, said the company, adding that GLP-1 agonists are known to cause a delay in gastric emptying, as noted in the label of these medications. “Symptoms of delayed gastric emptying, nausea and vomiting are listed as side effects,” it added.
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Way ahead
According to Jayadevan, stomach paralysis, the extreme adverse effect reported by some of the US women who were on semaglutide therapy, could be from the higher doses used for obesity, compared to the dose used for diabetes.
Gastroparesis could also be a result of diabetes itself or other factors such as viral infections. “Diabetes itself causes gastroparesis in some cases,” he said.
“In a patient with diabetes, it can be hard to tell whether it is the underlying diabetes, the drug or both that led to the condition,” the doctor said.
He, however, called for a more vigilant adverse event monitoring system for new classes of drugs that have not been in use for a long time.
“It is also true that in some cases, serious adverse events emerge only after years of using a medicine in larger numbers of patients,” said Jayadevan. “And, therefore, there should be increased post-marketing surveillance for all new classes of medications,” he added.
Meanwhile, Mithal also warned that drugs like semaglutide should be taken only on medical advice and should be stopped if there are significant side effects. “Also, those who have nausea, vomiting and reflux issues should not initiate this treatment.”
(Edited by Richa Mishra)