New Delhi: The blockbuster diabetes and obesity drug semaglutide, developed by Danish pharma giant Novo Nordisk, has already emerged as a favourite among affluent sections of society in India and elsewhere.
However, there are more reasons patients in advanced stages of metabolic illnesses may want to consider the medicine, which is being called one of the most significant medical inventions in decades.
A study published last month in the journal Kidney International has shown that the drug may also be highly effective at reducing inflammation — indicating far-reaching impact in lessening the risk of kidney and heart diseases for diabetics.
“The latest finding will prompt more diabetics to go for the medication and more clinicians to consider prescribing it to their patients,” Dr Anoop Misra, chairman of Fortis C-DOC Hospital for Diabetes and Allied Sciences, told ThePrint.
Semaglutide belongs to a class of medications known as glucagon-like peptide-1 (GLP-1) receptor agonists and is called a GLP-1RA drug. It mimics the GLP-1 hormone that is released in the gastrointestinal tract in response to eating.
One role of GLP-1 is to prompt the body to produce more insulin, which reduces blood glucose (sugar) and in higher amounts, also interacts with parts of the brain that reduce appetite and signal a feeling of fullness.
There are currently three US Food and Drug Administration (USFDA)-approved semaglutide products. These include the Ozempic injection and Rybelsus tablets, which are approved for lowering blood sugar levels in adults with type 2 diabetes mellitus, in combination with diet and exercise.
The third product is a higher strength of the medicine, under the brand name of Wegovy. It is available as an injectable and is approved to help adults and children aged 12 years and older with obesity or some adults with excess weight (overweight), who also have weight-related medical problems, to lose weight and keep it off, in addition to diet and exercise.
In India, only Rybelsus tablets, which have low strengths of semaglutide, are approved by the Central Drugs Standard Control Organisation, but many diabetics who can afford the costly drug get the imported injectables from the US.
Now the latest study, through which scientists in Australia and Canada used a new technique known as single cell sequencing to examine how semaglutide was working in the kidney, has identified a novel glucose-independent kidney-protective action of GLP-1-based therapies in diabetic kidney disease.
Diabetic kidney disease occurs in up to 40 per cent of individuals with diabetes and remains the primary cause of kidney failure worldwide. This number could be huge for India, which has an estimated 101 million people suffering from diabetes.
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What more can semaglutide do?
Previous research has shown that semaglutide reduces cardiovascular risk in people with diabetes. Another research paper that was published in December 2023 based on a large, international trial showed that even for people without diabetes, semaglutide may deliver cardiovascular benefits.
This had come in the wake of an announcement by Novo Nordisk in August that semaglutide had shown a statistically significant and superior reduction in major adverse cardiovascular events — of 20 percent — for people treated with 2.4 mg of the drug compared to a placebo.
Then, in October, the pharma giant announced its decision to stop FLOW — the kidney outcomes trial to gauge the effect of semaglutide versus a placebo on the progression of renal impairment in people with type 2 diabetes and chronic kidney disease.
“The decision to stop the trial is based on a recommendation from the Independent Data Monitoring Committee, concluding that the results from an interim analysis met certain pre-specified criteria for stopping the trial early for efficacy,” the company had said.
The latest research, meanwhile, demonstrates the importance of semaglutide-like drugs in the maintenance of kidney homeostasis (maintenance of water and electrolytes).
“It provides a rationale for investigating GLP-1RA for the treatment of non-diabetic kidney disease and highlights the glucose-independent renal benefits of GLP-1RA,” the scientists have said.
According to Misra, “The emerging evidence shows that semaglutide not only strongly reduces heart attack and stroke risk but also has salutary effects on the kidneys.”
“Another important effect is on liver fat and damage, where it shows impressive reduction, which has implications for prevention of cirrhosis — and these effects are as important as the drug’s primary impact on weight loss,” he added.
Chennai-based diabetologist Dr V. Mohan told ThePrint that semaglutide and other GLP-1RA medicines could go the way of SGLT2 inhibitors.
Also called gliflozins or flozins, SGLT2 inhibitors are a class of medications that inhibit sodium-glucose transport proteins in the nephron (basic structural and functional unit of the kidney) and their foremost metabolic effect is to inhibit reabsorption of glucose in the kidney, thereby lowering blood sugar.
“These drugs first started as medications to treat diabetes but later showed much advantage in treating chronic kidney disease, heart disease and heart failure,” Mohan said.
Likewise, he added, there could be many roles that breakthrough drugs like semaglutide play in treating diseases of the kidney, heart and liver — as shown by mounting scientific evidence.
“Going by the profound impact the medicine has on metabolism, I won’t be surprised if the drug is approved for multiple other indications,” he said.
But despite the long list of benefits that semaglutide and other similar drugs such as Mounjaro by Eli Lilly and Company bring, users are advised caution.
Gastroenterologist and medical researcher Rajeev Jayadevan had previously told ThePrint that side-effects from these drugs are common, especially nausea, vomiting, indigestion, diarrhoea, gas and bloating.
“Also, when the injections are stopped, patients tend to gain the weight back, especially if their food intake returns to previous levels,” he had said.
Also, other concerns with these drugs include some degree of muscle loss, risk of a fall and fractures, and how that might impact mobility in the long term.
(Edited by Nida Fatima Siddiqui)
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