Science.org declares – the 2023 Breakthrough of the Year to be a weight loss drug that can combat Obesity. Analysts predict the diabetes and weight loss market will be worth $100-150 billion by 2030.

Novo Nordisk A/S, a Danish pharmaceutical company, has become the largest publicly traded company in Europe with a market value of over $540 billion, following the launch of its drug Wegovy. This market value is now more significant than the gross domestic product of Denmark, which is the company’s home country. Novo Nordisk plans to invest between $5-7 billion over the next five years to enhance capacity.

Eli Lilly, the second pharmaceutical company to enter the market, has become the first to surpass a market value of $600 billion. This has been fueled by the recent release of Zepbound, a weight-loss shot that is predicted to become the best-selling drug in history. Some investors and analysts are even predicting that Lilly will become the first company in the industry to reach a market value of one trillion dollars.

According to a prediction made by the World Obesity Foundation in 2023, the economic impact of overweight and Obesity worldwide will reach $4.32 trillion by 2035 if current trends persist. The United Nations’ Sustainable Development Goals aim to reduce premature mortality caused by Obesity by one-third.

Obesity is a public health crisis. It was declared a disease in 2013 in the United States by the American Medical Association. In the USA alone, about 70% of adults are affected by excess weight, while a large percentage are obese. In Europe, that number is more than half as per the latest reports; WHO estimates that over 2 billion  ( 25%) of the world’s population is overweight.

Overweight is defined as a BMI ( Body Mass Index ) of 25 or above, while Obesity is defined as a BMI of at least 30. Obesity is thought to power type 2 diabetes, heart disease, arthritis, fatty liver disease, and certain cancers. The stigma against fat can be crushing; its risks are life-threatening. Social prejudice and anxiety create discrimination against obese humans in personal and work life.

Obesity is not only a first-world disease. As per studies, 20 % of the Indian population is overweight, with 5% to 7% of the population being obese. As per the Indian Council of Medical Research, India has become the diabetes capital of the world due to weight issues. There are over 101 million diabetics and 136 million pre-diabetic patients.

The Gila monster, a lizard, lurks in the deserts of the southern  U.S.. In the mouth of this creature, scientists discovered a chemical that would lead to the first glucagon-like peptide-1 mimic, the class of drugs honored as this year’s Science Breakthrough of the year 2023.

Glucagon-like peptide-1, or GLP-1 for short, is often called a gut hormone; it affects organs all over the body, from the stomach to the brain. It plays a vital role in regulating blood sugar, which leads to diabetes drugs. Early on, doctors noticed that people taking these drugs also often lost weight. Still, it wasn’t until the development of a version that could be taken weekly instead of daily that GLP-1 took off.

GLP-1 receptor agonists are highly effective weight loss drugs with limited and manageable side effects. Clinical trials suggest they improve heart health and kidney disease in people with Obesity or diabetes, and they’re being tested in other conditions, too. This year, clinical trials found that they also cut symptoms of heart failure and the risk of heart attacks and strokes, the most compelling evidence yet that the drugs have significant benefits beyond weight loss itself. Researchers theorize that the drugs bind to receptors in the brain that mediate the desire for other pleasures besides food.

The drugs didn’t catch fire until two years ago when Novo Nordisk’s, Wegovy was greenlit for weight management in the U.S. In a pivotal trial, people taking it lost an unprecedented 15% of their body weight over about 16 months. Many on the drug also describe a dampening of “food noise,” the relentless and distressing desire to keep eating.

Since then, the frenzy has only intensified. A trial of 529 people with obesity and heart failure found that after one year, people on Wegovy had almost doubled heart improvement. Novo Nordisk also announced that in a much larger trial of 17,000 people with excess weight and cardiovascular disease, people had a 20% lower risk of fatal or nonfatal heart attacks and strokes than those on placebo.

Medical breakthroughs are rarely straightforward, and the ebullience surrounding GLP-1 agonists is tinged with uncertainty. Like virtually all drugs, these blockbusters come with side effects and unknowns. Complications, including nausea and other gastrointestinal problems, lead some to abandon treatment.

Doctors also worry about people who aren’t overweight or obese turning to the treatment to slim down. Another worry is that GLP-1 agonists are “forever” drugs that people have to take indefinitely to preserve weight loss.

Researchers reported that two-thirds of their lost body weight returned one year after people stopped therapy. For researchers who increasingly consider Obesity a chronic condition, the need for ongoing treatment isn’t surprising. But the drugs’ cost can be prohibitive, with a sticker price of more than $1000 a month, and the prospect of lifelong use troubles many.

Eli Lilly, Zepbound is the next frontier in weight-loss treatments. It’s what’s called a dual agonist because it mimics the effects of two different hormones. The injection combines GLP-1 with another gut hormone, GIP, that helps lower blood sugar and may also increase metabolism. They cause more weight loss with potentially fewer side effects.

Will these blockbuster drugs turn the global obesity tide? And if so, for everyone, or just an advantaged few?

The “GLP1s” are expensive, and off-label use for weight loss will leave some with type 2 diabetes scrambling for their medications. Cost and supply constraints may further amplify health disparities. Those with insurance or resources to pay out of pocket will be the first to benefit. For others, these drugs will be out of reach.

Although standard safety profiles are favorable, what are the risks of taking these drugs for life? Does habituation occur? Will they dissuade people from regular exercise, which carries distinctive health benefits? And what is the abuse potential for extreme cosmetic purposes, for people with eating disorders, or for gaining an advantage in sports where leanness matters?

With about 70 new obesity treatments in development, six are awaiting regulatory review.

In the coming year, expect more companies to enter the final stages of trials and seek approval as demand skyrockets.