The truth about the new weight-loss drugs

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Friday, July 28, 2023
the truth about the new weight-loss drugs

 

Shivika (name changed on request) has been trying to lose weight for the last 10 years. When she was 65 kilos about two years back, her target was to lose 10 kilos. But now she is 78 kilos. Every time, she would go on a strict diet and exercise regimen, she would lose a couple of kilos but gained them back as soon as she relaxed her regimen a bit.

Shivika is not the only one who is struggling with obesity. In India, about 50 percent of women and 12 percent of men between 30 to 49 years of age have abdominal obesity, which increases their risk of developing heart issues, Type 2 diabetes, and joint-related problems. Worldwide, about 44 percent of people are living with obesity.

A dietician she recently consulted prescribed her a drug that contains salt called semaglutide. This oral drug has been approved in India for diabetes management. But,  in 2021, in a higher dose injectable form, it got FDA approval in the US and the UK, where it is available under the brand name Wegovy, as an anti-obesity drug. But Shivika is not sure if she should take the drug and wishes to seek a second opinion.

So, what are these drugs? And how do these help in reducing weight?

Basically, most of these drugs are GLP1 (Glucagon-Like Peptide-1) receptor Agonists. “This compound delays gastric emptying by decreasing peristaltic movement in the abdomen and promoting early satiety. Peristalsis is a series of wave-like muscle contractions that move food through the digestive tract. These GLP1 agonists manage diabetes by preventing sugar surge in blood after meals and are also now used for weight control. They also have some direct anti-inflammatory effects,” says Dr Manisha, a Chandigarh-based internal medicine specialist.

These compound delays gastric emptying by decreasing peristaltic movement in the abdomen and promoting early satiety. 

Besides, there are many new drugs that are in the different stages of trials to be used as anti-obesity drugs. These drugs target the natural receptors of two or three of these hormones. So, they are called dual or triple agonists. Take for example, tirzepatide, marketed as Mounjaro, is a dual agonist as it mimics both GLP1 and (GIP Gastric Inhibitory Polypeptide)—the two incretin hormones. Similarly, CagriSema, has semaglutide and amylin, is also a dual agonist. Then there is a triple agonist—Retatrutide—which stimulates receptors for GLP1, GIP, as well as glucagon. Another class of antidiabetic drugs -- SGLT2 Inhibitors-- which act by promoting glucose excretion in urine.

Most of these drugs are being used as anti-diabetes drugs and lead to 15-24 percent of weight loss in a year. These compounds, according to various researches, can lead to higher weightloss in a non-diabetic person. “Diabetes type-2 is more prevalent in people with obesity. When we prescribe Semaglutide to these patients, weightloss is a by-product,  but it helps maintain the blood sugar levels more effectively. In fact, not just Semaglutide but a few other anti-diabetic formulations also result in some degree of weight loss,” says Dr Anoop Mishra, executive chairman, Fortis C-DOC Hospital for Diabetes and Allied Sciences. 

Doctors say that obesity and diabetes are not entirely separate conditions; they are rather so inter-related that improving one of them leads to improvement in the other. “Abdominal obesity is associated with insulin resistance, increased oxidative stress, and low-grade inflammation. All these subsequently lead to diabetes mellitus. Thus, controlling obesity has always been an important part of diabetes treatment,” says Dr Manisha.

Obesity and diabetes are not entirely separate conditions; they are rather so inter-related that improving one of them leads to improvement in the other.

 

Firstly, doctors advise lifestyle modification to all diabetes patients to reduce weight and decrease fat mass. There are antidiabetic drugs such as metformin and alfa glucosidase inhibitors that do not let a lot of glucose go into your blood from your intestine at one time after you eat your meal. Metformin also decreases lipogenesis and decreases inflammation. Thus, these have been the drugs of choice in obese diabetic patients, although enough data and approval for using these drugs to treat obesity is not available.

In India, however, any of these drugs, including semaglutide, have not been approved to be used as anti-obesity drugs, but have been used off-label for obesity.

Gaining weight and then losing, doctors say, is a complex mechanism. In simple terms, a person eats so that the body can produce energy to meet its daily activities. When you eat more than you could use, the body stores the extra food in the form of fat. This fat keeps accumulating and leads to weight gain. If the person is eating extra every day, it also enlarges the stomach. An increased stomach size makes us more hungry and we tend to eat more to satiate the hunger.

“People erroneously think that the key to losing weight is reducing the calorie intake and burning more calories. Unfortunately, this false paradigm has been deeply ingrained in our minds. Weight regulation depends on a very complex neuro-hormonal system. It has nothing to do with a person’s willpower. Obesity is a result of dysregulation of these neuro-hormonal pathways,” says Dr Aparna Govil Bhaskar, a Mumbai-based bariatric surgeon.

“Unfortunately, as the weight increases, it becomes increasingly difficult to perform strenuous activities. Joint problems, backache, and breathlessness creep in. Pushing people with severe obesity to exercise too much can lead to potential injuries which is in turn counter-productive for any weight loss program”, says Dr Aparna. For such people, these  drugs along with diet and physical activities can be a more effective tool to battle obesity. “These drugs can help them lose a few kilos and motivate them to keep up with the weight loss program,” she says.

Besides, these drugs, when given to obese people with diabetes, have also shown a positive impact on their heart and liver. “In a recent American Diabetes Association conference, it was shown that these drugs can be useful for patients with liver fibrosis. They are even showing positive results in patients with clogged arteries,” says Dr Mishra.

So are these drugs an alternative to bariatric surgery?

“Drugs are just another tool to tackle obesity. However, as with any other disease, obesity also needs to be treated depending on its stage and severity. The total body weight loss achieved through drugs is significantly less as compared to bariatric surgery. I would say that drugs are not an alternative but an adjunct to bariatric surgery for the treatment of a very complex disease that is obesity”, says Dr Aparna.

“Bariatric surgery is a life-saving surgery, and not a cosmetic surgery,” explains Dr Pradeep Chowbey, Chairman, Max Institute of Laparoscopic, Endoscopic & Bariatric Surgery. “These drugs can be prescribed to patients with obesity and one more chronic illness. They are definitely not a replacement for bariatric surgery, which we prescribe to morbidly obese patients.”

Not so perfect

Well, like any other drug, these drugs too have certain side effects and contraindications. People with family history of thyroid tumours or cancers, women planning a family, and lactating mothers, should avoid taking them. In case of any swelling or inflammation in the throat, hoarseness in voice, patients should seek medical advice. In some rare cases, drug can cause inflammation of the pancreas.

 Nausea, gastric disturbance, and abdominal discomfort are their common side effects, which usually subside in a month or so. That’s why doctors, in the beginning, prescribe low doses of these medicines and gradually increase the dose over 12 to 17 weeks. 

The other deterring factor is that once started, these drugs have to be taken lifelong as stopping them may mean regaining the lost weight. And these are expensive drugs, costing anything between INR 85000-1,00,000 per month, an amount unaffordable for most Indians. But in the US, the demand for Wegovy is so high that the company is finding it hard to meet the requirement.

Undoubtedly, a pill to kill obesity, one of the fastest growing epidemics across the world, is a tempting choice for millions suffering from it, many doctors still believe that a majority of overweight and obese people should choose the conventional path—exercise, balanced diet, proper, sleep – to fitness.

“These drugs can never be an alternative to a healthy lifestyle, which if sustained, is still the best way to lose weight as it is free of side effects,” says Dr Chowbey.

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