BLOG

The new class of anti-obesity drugs like Ozempic, Wegovy, Zepbound remain the most popular modern drugs which continue to receive great attention on social media and have been celebrated as the “drugs of the century”. These long sought after “miracle” drugs have been shown in large randomized placebo controlled studies to reduce up to 20% of excessive body weight and – as long as you take them – maintain their effectiveness. Further flaming the public interest, recent preclinical and clinical research are suggesting that the same drugs which were originally developed as diabetes medications, may even be useful in the treatment of substance use disorders and may lower the risk of heart disease, such as heart failure, stroke and kidney disease.

“Obesity is a chronic disease that results in substantial global morbidity and mortality.”

According to the CDC, 40% of Americans are obese, and 32% are overweight. Soaring obesity rates make the United States the fattest country within The Organization for Economic Co-Operation and Development (OECD), a group made up of 38 countries in Europe, Asia and South America. Overweight and obesity rates have increased steadily since the 1980s in both men and women, and continue to grow. You only need to take a close look at the average body size while waiting for your plane at any US airport and you will see the prevalence of the problem. Three out of four people are projected by the OECD to be overweight or obese within 10 years.

While obesity for many individuals can be a serious cosmetic and social problem, compromising job opportunities and relationships, and often leading to discrimination (“fat shaming”) , obesity also plays a major role in the worldwide epidemic of chronic, non-communicable diseases, which include metabolic syndrome, type-II diabetes, cardiovascular diseases, neurodegenerative diseases and liver disease.

“Many previously tried interventions have failed due to side effects or lack of effectiveness.”

Dietary and behavioral approach are often successful in the short term, but a large number of patients regain their weight after successful diet-induced weight loss (often overshooting their pre-diet body weight, a phenomenon referred to as the YoYo effect). However, there are exceptions to this gloomy assessment. A study of over 4,000 people who lost weight as part of a structured weight loss program identified behaviors that dieters have used successfully to maintain their weight loss for more than three years. The reported behaviors included eating nutrient-dense foods, monitoring food intake, engaging in physical activity, goal setting and celebrating small achievements.

However, only a small percentage of dieters have the willpower to maintain such behaviors, and the medical system has evaluated several more dramatic interventions over the last decades. Invasive interventions like bariatric surgery (reducing the size of the stomach and rerouting the small intestine), endoscopic placements of inflatable balloons in the stomach to reduce its holding capacity and even endoscopic placement of openings and tubes in the stomach through which the stomach contents can be drained after a meal into an external bag!

“…these drugs have been criticized as the latest invention of the pharmaceutical industry to provide a lifelong therapy for a growing number of chronic disorders…”

Thus the development of a successful long-lasting treatment for obesity like the new anti-obesity drugs would seem like a remarkable accomplishment. At the same time, these drugs have been criticized as the latest invention of the pharmaceutical industry to provide a lifelong therapy for a growing number of chronic disorders, like hypertension, type-2 diabetes and hyperlipidemia, which puts a band aid on a societal problem directly related to an unhealthy lifestyle and the Standard American Diet. These critics suggest that the right approach to maintaining a normal body weight and preventing obesity-related chronic diseases is not an expensive pill, but a healthy diet.

These critics forget that the traditional treatment of obesity which has focused predominantly on lifestyle-based approaches, including calorie restriction, various forms of intermittent fasting, and different types of diets has failed to stop the worldwide obesity epidemic. One of the reasons for this failure is the fact that diet and exercise prompt physiological counterregulatory mechanisms that limit weight reduction and impede weight maintenance. Previous failures have led to the realization that obesity is a complex, multi-component metabolic disease of energy homeostasis involving multiple dysregulations within the brain-gut-microbiome system.

Given the seriousness of the problem, and decades of failed attempts to stem the progressive rise of the obesity epidemic, it is helpful to objectively weigh the pros and cons of this latest pharmacological approach to the obesity problem.

Pros:

If long-term studies confirm the sustained effectiveness of this class of drugs to counteract the current obesity epidemic, and to reduce the prevalence of the obesity- related chronic disease epidemic without serious long-term side effects, it may become a similar cost-effective treatment as our current medications for high blood pressure, abnormal blood lipid levels and diabetes, which prevent heart attacks and strokes.

However, only taking a pill everyday will not do the job. Based on the successful completion of several clinical trials with weight-loss drugs, including the new class of GLP-1 agonists, current treatment guidelines for obesity recommend anti-obesity medications in addition to diet and lifestyle modifications to promote weight reduction, facilitate weight maintenance, and improve health outcomes in people with obesity.

Cons:

These drugs do have potentially serious side effects as they interact with receptors widely distributed throughout the digestive system and the brain. Slowing of gastric emptying (gastroparesis), acid reflux, constipation, pancreatitis and thyroid tumors have all been reported. Recent evidence has demonstrated that these weight loss medications can also modulate the composition of the gut microbiome.

In addition, GLP-1 and GIP agonists are given in unphysiological high doses, interfering with our most important regulatory systems in the body (digestion and metabolism) in ways that are still incompletely understood. Chronically overstimulating these receptors has the potential to result in their downregulation and desensitization, shifting the system further away from its normal physiology.

“…some patients have actually had to remind themselves to eat…”

While these medications are deemed safe for patients diagnosed with the conditions Ozempic and Wegovy have been approved for, little to no research has been done on the side effects on the growing number of individuals who are using them for cosmetic weight-loss purposes. Due to the appetite suppressing qualities of these GLP-1 drugs, some patients have actually had to remind themselves to eat, which is why it is recommended to work with a dietician or nutritionist to make sure patients are getting adequate amounts of protein, vitamins and nutrients to properly nourish their bodies.

Like many of our most popular medications, anti-obesity drugs treat the symptoms but not the root cause of the problem. For many patients, starting such medications means a lifelong commitment to taking them, as weight gain will reappear as soon as they stop taking it. Based on these findings, one could say that for a number of patients, the GLP-1 agonists have the potential to turn food addiction into GLP-1 dependency!

While these drugs are a major breakthrough for patients with severe obesity and comorbid metabolic derangements, who have failed previous dietary and behavioral treatments, the widespread use for cosmetic weight-loss by overweight and mildly obese individuals should be discouraged.

Far from being a cure for the raging epidemic of non-transmissible chronic diseases related to obesity and associated metabolic disorders, it is just another super expensive band-aid, that will primarily benefit the profits of the pharmaceutical industrial complex.

For the number of patients who can afford them, taking these medications will decrease the risk for developing the well-known medical complication of obesity and metabolic syndrome without the need for difficult lifestyle modifications. It will allow the healthcare system and our politicians to get off the hook from address the societal and economic root causes of the problem.

A few questions should be addressed before endorsing the current weight loss craze: With the exception of some highly motivated and strong-willed individuals who will be able to maintain their healthy weight after losing the extra pounds, what percentage of people will be able or willing to dramatically change their lifestyles with vigorous daily exercise and a change of their dietary habits from the Standard American Diet to a calorie-restricted Mediterranean-type diet concept? What percentage of the population (in particular those in the lower socioeconomic segments of society, who are most affected by the obesity and chronic disease epidemic) will be able to afford a medication which currently costs more than $1000 a month?