For a long time, this Surat-based family had learnt to live with obesity and diabetes, reconciling with their bad genes. Till they were introduced to Semaglutide, the blockbuster weight loss drug that’s taken the world by storm, reshaping waistlines and controlling blood sugar levels. The 60-year-old patriarch is no longer insulin-dependent. His wife, sons and daughter-in-law lost between 15 and 20 kg in just six months. While the older couple managed their weight with Rybelsus, the oral form of Semaglutide (an antidiabetic and weight-loss medication) that’s available here, both their sons and daughter-in-law chose the faster-acting injectable, Tirzepatide, procuring them directly from the US.
With studies proving that injectables can reduce your weight by up to 20 per cent, comparable to life-saving bariatric surgeries, these are now expected to be available in India in the next couple of years. Regulatory data analysed by The Indian Express shows that advanced-stage trials for at least seven new drugs in this category have been listed with India’s clinical trial registry. Currently, there are 31 trials in place. Two of these medications are already approved for use among diabetics and those struggling with obesity in the US. Danish company Novo Nordisk sells the injectables under the name of Ozempic, a low-dose injectable for diabetes, and Wegovy, a high-dose injectable for weight loss. Similarly, Eli Lilly has rolled out Moujaro for diabetes and Zepbound for weight-loss.
Six of the seven therapies currently under trial are developed by Novo Nordisk and Eli Lilly. These drugs can be marketed here once the trials show positive results among a wider arc of our population.
WHAT THE INDIAN TRIALS ARE ALL ABOUT
The Indian Express analysed two important data sets: clinical trial registry data and the recommendations of the subject expert committee of the drug regulator. These show that several phase 3 global trials of the popular compound Semaglutide are under way in India to study the impact on diabetes management, weight loss, obesity-related heart diseases and chronic kidney disease. Latest global research and trials show that this wonder drug, called GLP1 receptor agonist, not only controls blood sugar but brings down blood pressure and cholesterol, thereby protecting heart health. A recent Novo Nordisk trial in the West has shown that Semaglutide slows down the progression of chronic kidney disease, preventing mortality from related complications.
While one study is looking at the effect of the drug on children and adolescents, a few others are studying its impact on diabetes-related complications like peripheral arterial disease (blockage of blood flow to the extremities) and diabetic retinopathy (damage to the retina). A phase 2 study is under way to see the impact of the medicine on patients with non-alcoholic liver damage.
How do these drugs work?
Semaglutide essentially mimics a hormone, called glucagon-like peptide 1 (GLP1), which stimulates the pancreas to produce more insulin, in turn lowering blood sugar, reducing craving and slowing digestion. All these mechanisms keep you satiated and prevent you from overeating, ultimately leading to weight loss. “While Wegovy is about to enter India and has shown about 10 per cent weight loss in participants, India is also participating in trials of more potent compounds. Tirzepatide, which acts on two targets — GLP-1 along with GIP — is more powerful and leads to about 15 per cent weight loss. The upcoming drug Retatrutide goes a step further and acts on three targets GLP-1, GIP, and glucagon, tackling obesity more effectively at 24 per cent,” says Dr V Mohan, chairman, Dr Mohan’s Diabetes Specialities Centre, Chennai.
With three companies working on dual-target drugs and another four companies on triple target drugs globally, Dr Mohan foresees fierce competition in the coming years.
INDIA NOW PART OF ADVANCE DRUG DEVELOPMENT
Determined to stay ahead of the curve, Novo Nordisk is now trialling Semaglutide with insulin Icodec and another weight loss compound Cagrilintide. Novo Nordisk recently announced early results for another weight-loss medicine called Amycretin, which like CargiSema targets GLP-1 and another hormone called amylin. The early phase 1 results, which are yet to be published, demonstrated a 13% weight-loss at just 12 weeks
While CagriSema is being studied for use by both diabetics and the obese, IcoSema, being an insulin compound, is being studied only for its efficacy among diabetics. IcoSema addresses the problem of weight gain in diabetics who need insulin shots to control their sugar levels, according to experts. At least four trials of CagriSema are under way, with 614 participants from India. Three trials for IcoSema are also ongoing with 320 participants from India.
Similarly, global trials are under way to assess the role of Eli Lilly’s Tirzepatide in managing type-2 diabetes, obesity and heart failure. At least eight trials for Tirzepatide have been registered with 1,088 participants here.
India is also a part of the company’s trials for its newer drug Retatrutide to test its glucose and body weight-lowering capacity. There are two trials of the Retatrutide, with 320 participants from India. Similar phase 3 trials are going on for another Eli Lilly compound called Orforglipron to study its effects on people with only diabetes, only obesity or both. There are at least four trials with 460 participants from India.
PREPARING FOR GENERICS
Dr Mohan expects a boom in generics when the US patents of these drugs expire. The molecules may have been developed in the West but once their patent expires, they can be produced here by those very companies or others. Local manufacturers introduce lower-priced generic versions, which are clinically equivalent to the original branded drug. Several Indian pharmaceutical manufacturers are already conducting these bio-equivalence studies to test the effectiveness of their generic products. For example, one of the patents of Semaglutide is set to expire in 2026.
Glenmark has already announced a generic version of an older drug, Liraglutide, which will be marketed as Lirafit. This will cost 70 per cent cheaper than the patented product. Other companies such as Sun Pharma, Levim and Biocon sought permission to conduct bioequivalence studies last year. Companies like Torrent and Dr Reddy’s, on the other hand, are conducting bioequivalence trials for Semaglutide injectables. “The launch plans will be in keeping with patent expiry,” said the spokesperson from Dr Reddy’s.
WHY THE DRUGS COULD BE A GAME CHANGER FOR INDIA
With most Indians reporting an onset of diabetes and heart disease at least a decade earlier than other populations, the drugs could change the map of non-communicable diseases in India. Especially after the latest Lancet study has flagged how India is rapidly moving up on the obesity curve. The new study reveals that 44 million women and 26 million men aged above 20 in India were found to be obese, this figure being 2.4 million women and 1.1 million men in 1990.
Despite such prevalence, there was a dearth of drugs to treat obesity both at home and abroad. As Dr Mohan explains, “The obesity drugs that came to the market before the GLP-1 receptor agonists led to just about five per cent weight loss but many of them had to be withdrawn because they led to side effects such as pulmonary hypertension (high blood pressure in the arteries of the lung), heart conditions, depression, and suicidal tendency. The good news is that GLP-1 drugs have been around for five to ten years without causing significant side-effects.” A 2016 review of anti-obesity drugs in BMC Medicine revealed that 25 of the older drugs were withdrawn from the market despite approvals between 1964 and 2009. Most of them had led to cardiotoxicity, drug abuse and other psychiatric problems.
In contrast, users of GLP-1 drugs have so far mostly reported nausea, vomitting, abdominal pain, bloating, diarrhoea and stomach paralysis in the initial stages. Still, many cannot tolerate these effects and give up midway. Now regulators have asked makers of these new categories of drugs to keep an eye out for psychological impacts like self-harm.
WHAT ABOUT SEVERITY OF SIDE EFFECTS RESULTING FROM MISUSE?
Unscrupulous ways of procurement have meant that the grey market for weight loss injectables is alive and kicking and led to gross misuse. While the drug works in controlling both diabetes and weight, people only see the latter. And they think it is just another OTC drug to be had at will. Dr Anoop Misra, chairman of Fortis-CDOC Centre of Excellence for Diabetes, Metabolic Diseases and Endocrinology, New Delhi, has already seen people with access to the drug misusing it and fears widespread availability will only worsen the situation. “We had a patient whose dietician prescribed Semaglutide without educating him about guidelines or the initial nausea. Neither did they escalate the dose slowly. Besides, the patient did not really need it as their body mass index (BMI) was 27 instead of 30, for which lifestyle interventions should have been suggested,” he said.
Everyone should first consult an endocrinologist and find out if they need it or not. Apart from nausea and vomitting, Dr Misra has come across a couple of cases of pancreatitis among users as well. “We have just seen the first case of thyroid cancer in one of our patients,” he adds. In the rush to shed kilos, people are overlooking if they qualify for these drugs in the first place. Dr Misra warns that it should not be prescribed to people who have a family history of thyroid cancers, have long-standing diabetes with sluggish peristalsis (contraction and relaxation of the digestive tract to push the food through), gastric obstructions and those who are prone to nausea.
IS YOUR WEIGHT LOSS PERMANENT?
While these drugs have offered hope to the obese, they are not the magic bullet and cannot work on their own without lifestyle interventions. As Dr Mohan says, “These drugs may get you off the weight cliff but lifestyle interventions of diet, exercise and adequate sleep have to continue. The drugs do not work the same way for all – about 25 per cent of people experience significant weight-loss and reduction in HbA1c levels (three month average of blood glucose levels), 25 per cent experience only weight reduction or drop in HbA1c levels and the other 25 per cent do not experience either.”
Dr Misra quotes recent research that shows the fat comes back once the drugs are discontinued and only a longer term usage can sustain weight loss. “We don’t even know whether they will keep working long term. With other diabetes drugs, we have seen how they have to be scaled up or the patient has to be moved to other drugs after a few years. We also do not know the long-term consequences of these drugs as they have been on the market for only a few years,” says Dr Mohan.
CAN EVERYBODY AFFORD THESE DRUGS?
Cost remains a big challenge, making these drugs more an elite privilege than a health benefit. The older drugs that are already available in the market can cost patients up to Rs 10,000 to Rs 15,000 a month. Long-term use would be a drain on the resources. This could spiral further with the new drugs. “For at least 30 per cent of the patients, the price of these drugs is a major deterrent,” says Dr Misra.
This is likely to change as more and more generics enter the market. “There will be an explosion in the use of these drugs after 2026 when the patent for one of the formulations of Semaglutide expires. The patent for the oral version of the drug will end in 2031,” says Sheetal Sapale, president, marketing, AIOCD, AWACS, a pharmaceutical research company.
There is already an existing market which will be capitalised by these drugs. “Obesity is now affecting the young and children – these are the people who wouldn’t mind spending to remain healthier. This, combined with companies reaching out to people through social media testimonials, has built an expectation and a demand,” she adds. Question is can these drugs become a tool for public health management in the long run?
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