New Delhi: Semaglutide, a fat-busting weekly injectable that has been a global smash hit since its launch five years ago, may soon have a successor that promises to be even more effective in shedding those extra kilos. On a call with investors last week, Danish drugmaker Novo Nordisk shared some teasers about CagriSema, the next generation of semaglutide which is sold under the brand names Ozempic (for diabetes) and Wegovy (for obesity). This has created massive buzz internationally and expectations that it may be even more potent in managing obesity—a disorder linked to several metabolic conditions.
Novo Nordisk’s executive president of development Martin Holst Lange told the media and investors in London that larger trials are likely to show that CagriSema — currently in the phase III trial — will help users lose up to 25 percent of their weight , adding that the company used data from previous trials to arrive at that number. Semaglutide helps regulate blood sugar levels, and works by binding to receptors of the gut hormone Glucagon-like peptide – 1 (GLP-1). It contains a compound known as (GLP-1) receptor agonist, which mimics the naturally occurring gut hormone known to send signals of a full appetite to the brain.
It is known to reduce body weight by around 15 percent after 68 weeks on average. On the other hand, semaglutide’s close competitor tirzepatide —a drug by US pharma firm Eli Lilly and Company which is available under brand names Mounjaro (for diabetes) and Zepbound (for obesity)—works on another gut hormone, gastric inhibitory polypeptide (GIP), in addition to GLP-1. This drug has shown a maximum weight loss of 20 percent at the highest dose strength after 72 weeks.
CagriSema combines semaglutide with cagrilintide, which targets the pancreatic hormone amylin that regulates glucose levels and food intake. The drug is currently in a phase III clinical trial, and the final results of its effectiveness on obesity management are expected within the next three months, the company said in response to a query by ThePrint. “It is the first in a new class of nutrient-stimulated hormone-based therapies, offering a unique dual mode-of-action that combines cagrilintide, a long-acting amylin analogue, with the proven, weight loss potential of our long-acting GLP-1 RA (receptor agonist) semaglutide,” the company further stated.
Also Read: Desperate Indians want Ozempic on prescription. Huge shift from traditional drugs, say doctors Until now, semaglutide and tirzepatide are two drugs that have been hogging the limelight globally for their weight loss effects. However, the injectable versions of neither of these drugs are available in India yet, despite regulatory approval from the Central Drugs Standard Control Organisation (CDSCO), mainly due to supply issues.
An oral version of semaglutide, however, under the brand name Rybelsus, has been available in the country in 3 mg, 7 mg, and 14 mg formulations and is indicated for type 2 diabetes. In June last year, Eli Lilly released data from a phase II clinical trial of its investigational drug retatrutide—a triple agonist—in obese patients, which showed that those taking the drug lost up to 24 percent of their body weight in 48 weeks. According to results of the phase II trial of CagriSema, which combines 2.
4 mg of semaglutide (also used in Wegovy) and cagrilintide, within week 32 of treatment, it caused a decrease in body weight by 15.6 percent from baseline. The results were released in August this year.
“The results from phase II trial of the drug indicates that it may have better results in controlling obesity as compared to semaglutide, tirzepatide and nearly same or slightly better than even retatrutide at the end of the trial period,” a senior endocrinologist in Delhi, who did not wish to be named, told ThePrint. All these drugs that have shown remarkable effects in managing obesity, work by binding to receptors of various gut hormones, he added. These receptors regulate secretion of pancreatic hormones as well as gut function, and their malfunctioning aggravates type 2 diabetes and obesity.
The drugs have the effect of creating a feeling of fullness for longer and thus reduce appetite. Also, weight loss is believed to occur at the central level (hypothalamus), where these drugs reduce appetite and promote early satiety. Novo Nordisk told ThePrint that it is conducting separate phase III programmes with CagriSema in type 2 diabetes and obesity.
The phase III trial programme in type 2 diabetes, REIMAGINE, was initiated last year and is expected to be completed in 2025-26. The phase III trial programme in obesity, REDEFINE, was initiated in 2022 and is likely to be completed in 2024-2025, with first data expected this year, it said. The endocrinologist quoted earlier, meanwhile, warned that the new age obesity drugs, even though they are also showing significant results in managing and preventing other conditions such as cardiovascular diseases, chronic kidney disorders and even mental illness , are also associated with some side effects.
Nausea, bloating, vomiting and diarrhoea, for instance, 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. “CagriSema is also expected to have the same side-effect profile even though data from the phase III trial will shed more light on it,” he said. It is estimated that there are nearly 823 million people across the world suffering from obesity while under 2 percent of them are treated for it, according to details shared by Novo Nordisk in its Q3 results last week.
The World Health Organization (WHO) defines obesity as a body mass index (BMI) a BMI of 30 kg/m2 or higher for adults and “a BMI of more than two standard deviations above the median of the WHO growth reference for children and adolescents”. The WHO growth reference for children and adolescents is the standard devised by the WHO to measure weight and height of people in the 0-20 years age group. A global study released in The Lancet this year had shown that in 2022, 82.
5 million Indians were classified as obese. Conducted by the NCD Risk Factor Collaboration (NCD-RisC) in association with the WHO, the study highlighted that approximately 9.8 percent (or 44 million) of Indian women, and 5.
4 percent (or 26 million) of Indian men, fell in the obese category that year. A survey conducted by Novo Nordisk, involving over 2,000 people living with obesity in India and 300 healthcare professionals which was released this month, showed that a high number of such people had have anywhere between 1 and 4 comorbidities, such as high blood pressure (32 percent), high cholesterol (27 percent), eating disorder (23 percent) and cardiovascular diseases (19 percent). Obesity is a complex, chronic condition that goes beyond just lifestyle choices and must be recognised as a disease in its own right, said Dr Ashutosh Goyal, senior consultant (endocrinology) with Paras Health in Gurugram.
“It significantly increases the risk of numerous health problems such as type 2 diabetes, heart disease, and high blood pressure. Treating obesity effectively requires a multifaceted approach, which includes not only lifestyle changes but also medical interventions. GLP-1 and dual GLP-1/GIP receptor agonists have emerged as effective treatments that help regulate hunger, promote satiety, and support sustainable weight loss by mimicking natural hormones in the body,” he added.
These medications can play a critical role in managing obesity and improving overall health outcomes, particularly for patients also dealing with type 2 diabetes, Goyal also said. (Edited by Gitanjali Das) Also Read: Low-sugar diet in 1st 1,000 days of life lowers risk of diabetes, hypertension in adults—Science study var ytflag = 0;var myListener = function() {document.removeEventListener('mousemove', myListener, false);lazyloadmyframes();};document.
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Ozempic on steroids? Successor that could cut down weight in half the time coming soon
While Novo Nordisk says CagriSema will help users lose up to 25% of weight, duration will be clear when final results of its effectiveness in obesity management come out in 3 months.