Thirty-nine-year-old Kerala physician Dr Zubair Nabin K* had been a chubby child who grew up to be an obese adult. Happiness for him was eating an extra portion of biryani or a pastry afterwards. Eating was never about nourishing the body, rather it was meant to turn a bad day around. Trapped in the cycle of dieting and overeating, his weight climbed to 120 kg. Being a doctor, he knew exactly what obesity could do to his health. He counselled patients about lifestyle diseases every day, yet found himself unable to break free from his own emotional relationship with food. “I had to turn myself around, there was no option,” he says.
While he lost a good 10 kg by dieting and exercising, he needed something more to reach closer to the recommended weight for his height, given his family history of obesity. He decided to enrol himself in the trial for a new GLP-1 drug called retatrutide two years ago. The drug is not yet approved for use in patients.
“The weight-loss was phenomenal. While I did not reach the ideal weight of around 70 kg, it was the first time in more than a decade that I saw two digits on the weighing scale,” says Dr Nabin. He had dropped to 89 kg. Before taking the drug, he would eat twice what a normal person his age did, predisposed as he was to a stronger appetite and a body that resisted weight loss. Afterwards, he could only nibble on his meals. He started choosing healthier options over fried snacks. “Giving up the biryani did not feel difficult,” he says. The changes in his physique — all clothes started fitting him better, his waist size dropped from 44 inches to 36 inches — came with a change in personality as well. “I was bullied as a child, but post-trial, I felt confident. I was not overthinking.”
What is retatrutide?
Retatrutide is an experimental weight-loss and diabetes drug and belongs to a new generation of medications that targets three different hormone receptors at once. All obesity drugs are incretin mimetics — they mimic the action of certain gut hormones by activating the same receptors, helping control blood sugar and suppress appetite. They improve secretion of insulin, inhibit secretion of glucagon that stimulates glucose production in the liver, and reduce appetite by slowing down digestion. While semaglutide targets GLP-1 receptors, tirzepatide goes for GLP-1 along with GIP. Retatrutide has three targets — GLP-1, GIP, and glucagon.
In a Phase 3 clinical trial, participants at the 80-week mark and on the lowest 4 mg dose, lost 19% of their body weight. Those on 9 mg lost 25.9%, and those on the highest 12mg dose lost 28.3% of their body weight, showed a phase III trial of the drug. This is among the largest weight reductions seen with an obesity medication at that stage of development. Some participants continued to lose weight beyond the end of the study, suggesting even greater reductions might be possible with longer treatment. For comparison, semaglutide produces around 15% average weight loss over about 68 weeks and tirzepatide around 20–21% over 72 weeks.
Coming to terms with body image
This sudden, significant weight-loss, however, has had some undesirable social outcomes as well. While the weight loss boosted the doctor’s confidence, looking into the mirror was still a challenge. “I could see that I had lost muscles. My shoulders and arms looked smaller. I felt like I was losing strength,” says Dr Nabin, who was a part of the retatrutide trial at Dr Jothydev Kesavadev’s Diabetes and Research Centre in Kochi.
Dr Kesavadev found that the sudden weight loss impacted the body image of all his trial patients in the initial days. He even presented a study at the recent American Diabetes Association, showing that people stopped using GLP-1 drugs not just because of side effects but also negative comments about their bodies. The study, though small involving 167 participants, reported how they received comments such as, “you have become too thin, this does not look healthy”; “are you not eating properly”; “you look so old”; or “you looked better before.” The study recommended that people must look at actual health parameters rather than perceptions. They should track their blood glucose levels, their blood pressure, their cholesterol levels and their inflammation.
“I know several people from my trial who started avoiding social events because people kept asking them whether they were okay, whether they were in good health. They understood that the people were asking them politely whether they had cancer. Most of them were obese at the start of the trial, so the weight-loss was very visible,” says Dr Nabin.
While he did not do any strength training before starting on the drug, he started going to the gym to gain back lost muscle mass. Another patient lost more than 25 kg with the widely available GLP-1 drug tirzepatide. He used to weigh 160 kg and was almost bed-bound. The weight-loss has helped him move around. Now, the challenge is the extra skin on his abdomen that hangs like a flap and needs fixing through surgery.
Dr Kesavadev believes that with powerful drugs such as retatrutide, bariatric surgeries would be a thing of the past. “The other weight-loss drugs from this class can already replace nearly 70% of bariatric procedures. With this drug, this proportion can increase to 95%. Only those who cannot tolerate the drug or are unable to take it because of contra-indications would need surgeries,” he says.
The battle with side-effects
Throughout Dr Nabin’s two-year weight-loss journey, every shot of the drug was followed by a bout of diarrhoea. “Every week, after I took my shot, I knew what was about to come. A bad taste in my mouth was the indicator. While it has never been severe enough to warrant hospitalisation — some patients do need to be hospitalised to prevent dehydration with severe diarrhoea — it affected my work, compelling me to take leaves once or twice every month,” he says.
Another side-effect that Dr Nabin has learnt to live with is dysesthesia — an unpleasant or abnormal sense of touch. “I have a tingling sensation whenever I wrap my mundu tightly around my waist. There is a sensitivity around my thighs, too,” he says.
While most of the side-effects of retatrutide are similar to that of other GLP-1 drugs, including diarrhoea, the phase III trial of the drug showed dysesthesia occurred in 5.1% to 12.5% of the participants.
Dr Kesavadev says several trial participants also reported this unpleasant sensation when there was some pressure on their skin. The theory is that this sensation is a result of the fat loss at the end of the nerves. “This usually happens in those on higher doses but we have seen it even in people on the lower dose. Gastrointestinal side effects like vomiting, diarrhoea and nausea happen with early dosing, dysesthesia can happen at any time,” he adds.
Now that the trial is over, Dr Nabin is on other GLP-1 drugs. “I have started gaining weight. Given my family history, I need medication for a longer period perhaps,” he says. As newer drugs such as tirzepatide and experimental agents like retatrutide become available, long-term treatment options are likely to expand. “But none of them will work without the supportive pillars of diet, exercise, sleep and a lifestyle overhaul. Newer drugs will come but they need your effort to work,” adds Dr Kesavadev.
(*Name changed to protect privacy)
