New Delhi: Move over semaglutide and tirzepatide, enter retatrutide — the latest and most promising contender to emerge in the realm of weight loss drugs.
According to phase-2 clinical trial data by pharmaceutical company Eli Lilly, released Monday, obese patients taking the drug lost up to 24 per cent of their body weight in 48 weeks, equivalent to an average of about 26.3 kg.
The findings of the trial, which involved 338 participants, were published in the New England Journal of Medicine.
A separate paper in The Lancet, also published Monday, analysed the drug’s effect on people with both obesity and diabetes, and found “clinically meaningful improvements in glycaemic control and robust reductions in body weight”.
Both papers were presented this week at the American Diabetes Association Scientific Sessions in San Diego, garnering an enthusiastic reception from physicians and diabetologists, including those from India.
“It’s amazing data — something that no drug has shown before and was unthinkable a few years ago,” said Dr Ambrish Mithal, chairman & head – endocrinology & diabetes, Max Super Speciality Hospital, Saket and Max Hospital, Gurugram, speaking to ThePrint from San Diego where he attended the conference.
Dr Anoop Misra, chairman of Delhi’s Fortis-C-DOC Centre of Excellence for diabetes, metabolic diseases, and endocrinology also said that while these are early-stage trials, this kind of weight loss has not been seen with any drug previously.
“If confirmed with further research and proven safe it would be a magical drug,” he told ThePrint.
Retatrutide works in a manner that is similar to its predecessors semaglutide and tirzepatide. It is administered as a weekly injection and brings about a shift in patients’ eating habits by imitating specific gut hormones.
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Reigning weight loss stars
Thus far, two other drugs that work on gut hormones have been hogging the limelight globally for their weight loss effects.
The first is semaglutide, developed by Danish drugmaker Novo Nordisk and sold under the brand names Ozempic, Wegovy, and Rybelsus.
The second is Eli Lilly’s tirzepatide, approved for medical use last year in some countries and sold under the brand name Mounjaro.
Various formulations of these drugs, mostly in the form of weekly injectables, have been indicated and approved for treating type-2 diabetes, but have also shown promising results in tackling obesity.
Eli Lilly has sought approval by the US Food and Drug Administrator (USFDA) to introduce Mounjaro exclusively as a weight loss drug, thus targeting people without diabetes too.
An oral version of semaglutide, under the brand name Rybelsus, is also available in India in 3mg, 7mg, and 14mg formulations, Mithal said.
In India, this drug has been indicated for treating only type-2 diabetes by the Central Drugs Standard Control Organisation.
According to Dr. Rajeev Jayadevan, a clinician and medical researcher based in Kerala, medications like semaglutide, tirzepatide, and retatrutide work by binding to receptors of various gut hormones.
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.
“Weight loss is believed to occur at the central level (hypothalamus) where they reduce the appetite and promote early satiety,” Jayadevan said.
What sets retatrutide apart from other drugs in its class?
While semaglutide targets a receptor called glucagon-like peptide-1 (GLP-1), tirzepatide works on both GLP-1 and gastric inhibitory polypeptide (GIP). Retatrutide, on the other hand, works on three receptors.
The first to come along was semaglutide (Ozempic).
“The drugs that have been developed over the last few years, like Ozempic, have mostly targeted GLP-1 receptors,” Mithal said. “Such drugs were able to cause more weight reduction than any other drug.”
Tirzepatide (Mounjaro) then arrived on the scene.
“Mounjaro is a dual receptor agonist which targets both GLP -1 and GIP and with Mounjaro. For the first time, researchers could reach around 20 per cent weight loss particularly in those who do not have diabetes,” Mithal explained.
Now, retatrudide is changing the game yet again.
“The findings about retatrutide come as a huge advancement because it is a triple receptor agonist that targets glucagon, GLP-1, and GIP,” said Mithal. “It is fantastic as it has shown weight reduction in the range of 24-25 per cent.”
According to the phase 2 clinical data published in the NEJM, 338 adults who were obese or overweight participated in the study. The volunteers were randomised to receive a placebo or one of four doses of retatrutide. The drug was given as a weekly injection.
After 24 weeks, participants taking the highest dose — 12 milligrams — lost, on average 17.5 percent of their body weight. By 48 weeks, the weight loss increased to 24.2 per cent of their body weight.
In comparison, Novo Nordisk’s semaglutide has shown to reduce body weight, on average, by around 15 percent after 68 weeks. Tirzepatide or Mounjaro has been shown to reduce body weight, on average, by 22.5 per cent after 72 weeks.
‘Game-changer’
Mumbai-based diabetologist Dr Rajiv Kovil, chairman of Zandra Healthcare, called the results from retatrutide “phenomenal and a possible game-changer.”
“Obesity is the mother of all disorders and especially non-communicable diseases. It drives diabetes, hypertension, dyslipidemia (elevated cholesterol), cancers, non-alcoholic fatty liver disease, and chronic kidney diseases globally,” he said. “If the burden of obesity can be reduced in a population, the burden of all these NCDs can be reduced.”
Kovil added that patients with diabetes could possibly benefit tremendously from the drug.
“The best of the retatrutide trial has been that with higher doses almost 83 percent of the participants lost almost 15 percent of body weight — which is enough to cause remission in diabetes and also cause morphological changes in the pancreas, making it function much better,” Kovil said.
He pointed out that another important finding was that weight loss in participants had not plateaued at the end of 48 weeks. “So, the drug can potentially achieve more than what the trial has shown so far,” he said.
Concerns over price, side effects
While drugs like semaglutide, tirzepatide, and now retatrutide have shown promising outcomes, doctors caution that they may come with side effects.
Such drugs also do not come cheap. For instance, even a blister pack of Rybelsus tablets in India costs a few thousand rupees and doctors claim that some patients obtain the injectibles from abroad.
Jayadevan said that drugs that work against receptor proteins have been around for several years.
“Almost all these drugs are expensive injections, and have helped wealthy obese patients with diabetes in India lose weight and attain better control of blood sugar,” he said.
According to Jayadevan, side effects 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 pointed out.
Mithal said that another concern could be some degree of muscle loss, risk of falling and fractures, and how that might impact mobility in the long term.
“To understand these things better, we need more data about the drug,” he concluded.
(Edited by Asavari Singh)