According to figures from the World Health Organization (WHO), obesity has reached epidemic proportions globally. The majority of people on earth now live in regions where overweight and obesity kill more people than hunger. In 2016, more than 1.9 billion adults were overweight, of which over 650 million were obese, corresponding to 39% and 13% of the world’s population. Overweight and obesity affects almost 60% of adults in Europe and over 70% in the US, with both proportions on the rise. Worryingly, this upward trend also applies to children, with the WHO labeling childhood obesity is one of the most serious public health challenges of the 21st century.
Upwards of 4 million people die each year as a result of being overweight or obese, but obesity is also related to many other diseases. Associated health consequences – well documented across myriad independent studies – include cardiovascular diseases (the world’s leading cause of death), type 2 diabetes, musculoskeletal disorders (including osteoarthritis), as well as sleep disorders and mental health issues. Moreover, being overweight or obese is linked with a higher risk of at least thirteen different types of cancers, including ovarian, breast, prostate, liver, kidney, and colon cancer. It all paints a rather large, bleak picture of the future if this epidemic isn’t addressed.
New drugs approved
Obesity is a chronic biological disease. This simple fact has long been accepted by scientists, but is only now finally becoming more widely acknowledged among the public and policymakers. For a long time, overweight people have been burdened with the stigma that they simply lack the willpower to eat less and exercise more. However, study after study have shown that it’s not simply about willpower: genetics contribute to obesity, and people’s metabolism and hormones often work against them as they try to lose weight. Unfortunately, changes in diet and exercise alone aren’t enough to achieve substantial and sustained weight loss.
Pharmaceutical companies have seen the growing demand for weight loss solutions and begun developing an arsenal of drugs. In particular, three recent FDA approvals have been gaining copious amount of attention: Wegovy (approved for weight loss, Novo Nordisk), Ozempic and Mounjaro (approved for type 2 diabetes, Novo Nordisk and Eli Lilly). The demand for these new drugs has been so high that off-label use of Ozempic and Mounjaro as weight-loss aides caused shortages for diabetes patients in early 2023 (worsened by viral celebrity endorsement).
“By reducing a patient’s desire to eat, incretin-mimetic drugs can lead to a startling amount of weight loss: 15-20% of the patient’s body weight, in clinical trials.”
Wegovy, Ozempic, and Mounjaro all belong to a drug class called incretin mimetics, which emulate the effects of the hormone GLP-1 (in Wegovy and Ozempic), or both GLP-1 and GIP (in Mounjaro). Incretin peptides like GLP-1 and GIP dampen appetite and increase satiety. By reducing a patient’s desire to eat, incretin-mimetic drugs can lead to a startling amount of weight loss: 15-20% of the patient’s body weight, in clinical trials. Proponents argue that these newly approved drugs offer a much-needed alternative to bariatric surgery, but the approval of these drugs has the potential for a much wider impact if they also help bring about a revolution in how we view and treat obesity.
Limitations and concerns
Obesity is a complex, heterogenous, and multifactorial disease. But surprisingly – and despite the epidemic gripping the world – the diagnosis, biological understanding, and healthcare management of obesity is still in its infancy. Critics of these newly approved drugs worry that their availability may tempt physicians to opt for an ‘easy’ treatment route, simply prescribing these new medicines without further analysis into the root causes of each patient’s weight gain. Unfortunately, we know that these underlying drivers are numerous and often overlapping, including an excess of insulin secretion, stress, sugar addiction, genetics and epigenetics, and early life experiences. These drivers also intersect and develop over time in response to environmental factors.
“These drugs are not curative… once patients cease taking the medication they regain, on average, two-thirds of previously lost weight within one year.”
Another issue is that the prescription of these drugs is currently based on a rather arbitrary qualification method: the patient’s Body Mass Index (BMI). This is a measure of a person’s body fat based on height and weight; a BMI over 25 is considered overweight, and over 30 is obese. While convenient and easy to measure, the BMI has several limitations when it comes to acting as a gatekeeper metric for treatment eligibility, including the fact that not everyone with a high BMI will necessarily develop metabolic disease, while some with a low BMI will.
More importantly, despite their efficaciousness in driving weight loss, these drugs are not curative – they do not address the underlying cause of patient’s obesity. Clinical studies showed that once patients cease taking the medication they regain, on average, two-thirds of previously lost weight within one year. Similarly, many of the improvements seen while on the medication (e.g. improved blood glucose and blood pressure), revert to baseline levels, leaving the patient hardly better off than when they started. Experts have already flagged that patients may have to keep taking these drugs for a lifetime to maintain their effects. However, there are as-of-yet no data on how the drugs affect people when taken over decades. This is especially concerning with Wegovy having been approved for the treatment of adolescents.
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Another consideration is the cost. With the extremely high prevalence of overweight, the diabetes and obesity market could easily top the blockbuster sales of statins in the coming years – Pfizer CEO Albert Bourla estimates that the market will grow to staggering $90 billion by 2028. Prescribing these drugs to patients (simply based on their BMI) – with an annual price tag in the US of $13.000 – could soon lead to a significant strain on healthcare systems.
You say you want a revolution?
Despite their limitations, these recently approved obesity drugs are a first step in the right direction for patients’ health. They are helping to shine the spotlight on obesity as a highly relevant indication and a global public health concern. Competition is now mounting across the pharmaceutical industry, with several new incretin-like drugs in development in various company pipelines. The investment space is also wide open for more differentiated drugs that better address the root causes of obesity, help patients lose fat while maintaining muscle mass, and provide more affordable, sustainable, and curative solutions.
Potentially the most impactful thing these new drugs can do for us is to help shift the perspectives of the public, industry, and healthcare systems towards viewing obesity as a complex biological disease, rather than an individual issue of poor lifestyle choices and weak will.
