The impact on public health would be tremendous. In the United States alone, the numbers are staggering – nearly 1 in 3 adults are overweight, over 2 in 5 adults are obese, and nearly 1 in 11 adults are severely obese, according to the NHANES 2017-2018 data. But what if we could significantly reduce obesity rates and improve the overall health of our nation?
One endocrinologist estimated that the prevalence of Type 2 diabetes would decrease by 80%.
We know that for each pound of excess weight, our knees experience four pounds of excess stress. Would the volume of hip and knee replacements drop dramatically? What about all the disease states either caused by or exacerbating other health challenges?
What would happen to the volume of strokes, the incidence of cardiovascular disease, the prevalence and severity of inflammatory disorders, and the volume of liver transplants resulting from NASH*?
* (nonalcoholic steatohepatitis, which is a fatty, inflamed liver not caused by heavy drinking)
It is estimated that 75+% of healthcare spending in the US is for the care of chronic diseases that were predominantly resulting from poor lifestyle choices. It is no surprise then, that there are new weight loss drugs incoming, although there have been previous attempts. Will the raft of incoming drugs for obesity be that finger snap, and why haven’t previous drugs performed as expected?
The History of weight loss
The quest for effective weight loss methods is not a recent phenomenon. The majority of beliefs regarding weight loss were developed in the 1950s and 1960s, primarily focusing on women who needed to lose a few pounds. The modern landscape is a completely different affair. However, the mainstream attitudes and diets are still very much centred around the thinking of that past era.
The challenge that faces us is that modern society generally carries far more weight than those in the fifties and sixties. Rather than a few pounds, many who are suffering from the effects of excess weight, need to lose tens of pounds. In extreme cases, over a hundred pounds. We need to be thinking differently.
Obesity was only categorized as a ‘disease’ in 2013. Over 40% of Americans are now considered obese and many Western nations are experiencing a weight issue among men and women of all ages. Even children are suffering. Sedentary lifestyles, junk food and alcohol are the major culprits.
The Broader Effects Of Obesity
The impact of obesity on healthcare costs is substantial. For example, consider the strain on hospitals due to obesity-related issues. Each pound of excess weight puts four pounds of additional stress on our knees, leading to increased joint problems and the need for surgeries like hip and knee replacements.
We seem to be in a situation where people are slipping into a weight issue and then are unable to reverse the trend. Some focus on personal health, use gyms regularly, eat the right foods and can police their weight. However, it is fair to say that a significant number of the world's population are finding that process a challenge. Economics plays a role too. Organic food, gym membership and access to information are often the preserve of those with a reasonable level of income. In deprived areas, cheap and processed food often exacerbates weight problems.
Education is not in and of itself an answer. Sure, many people are aware of what BMI means in literal terms. However, discussions around BMI (Body Mass Index) can be misleading. While it is a commonly used indicator for obesity, it does not consider the individual's body composition or overall health. In other words, you may be within the realms of an acceptable BMI and still need to lose weight.
Society needs us to be fitter and healthier. At an individual level, the benefits are irrefutable. So, why is obesity such an issue?
The answer is complex and varies according to personal circumstances. What we know is that people are more inclined to stay engaged with a weight loss programme if they see quick results. There is an in-depth study on myths and misconceptions relating to weight loss, here.
Factoring in the economic, social and psychological barriers to achieving weight loss, weight loss drugs are a viable and ethical solution in principle.
How do Weight loss drugs work?
There are different types of weight loss drugs, some acting on the central nervous system (CNS) and others on the gut. Perhaps the most notorious of all the weight loss drugs is Fen-Phen.
The Fen-Phen debacle remains a cautionary tale in the history of weight loss drugs. Fen-Phen was a combination of two drugs: fenfluramine and phentermine. It gained popularity in the 1990s as an effective weight loss solution, but its impact and aftermath were far from positive.
The Impact of Fen-Phen
Initially, Fen-Phen showed promising results, and many individuals turned to it as a solution to their weight struggles. It was believed that combining fenfluramine, which suppressed appetite, with phentermine, an amphetamine-like stimulant, would lead to greater weight loss than either drug alone. At its peak, millions of prescriptions were written for Fen-Phen.
The Aftermath:
However, the euphoria surrounding Fen-Phen's potential was short-lived. Serious adverse events started emerging, and it became evident that the drug combination was linked to severe heart valve issues and primary pulmonary hypertension (PPH). PPH is a rare but life-threatening condition that affects the lungs' blood vessels, leading to high blood pressure and, in some cases, heart failure.
As the reports of heart-related problems mounted, the FDA took action. In 1997, the FDA requested the voluntary withdrawal of fenfluramine and dexfenfluramine (another drug similar to fenfluramine) from the market. A year later, in 1998, the FDA officially banned these drugs due to their association with serious cardiovascular risks.
Fen-Phens’s Impact on Trust in Weight Loss Drugs:
Fen-Phen severely damaged the public's trust in weight loss drugs. Many individuals who had taken Fen-Phen were left with long-term health issues, and some even lost their lives. The incident raised questions about the safety and effectiveness of weight loss drugs in general. As well as body fat, any drugs that followed would have to shift a growing weight of opposition and prejudice.
Two drugs expected to significantly impact weight loss were Qsymia (phentermine/topiramate) and Contrave (naltrexone/bupropion), approved in the US in 2012 and 2014, respectively. However, they did not deliver the expected results.
Let’s focus on Contrave as an example. In clinical trials, patients on Contrave lost only 5.6% of their initial body weight after 56 weeks as opposed to the 20%+ threshold that is seen as an acceptable target. 24% of patients dropped out of the trial because of adverse events. The drug also has a black-boxed warning for suicidality.
Read the clinical data on Contrave here.
Post-Fen-Phen and Drugs with Mediocre Effect and Adverse Events:
Despite the setbacks and challenges faced by Fen-Phen and subsequent weight loss drugs, the search for effective and safe weight loss medications continues.
Phentermine, the "Phen" part of Fen-Phen, is still prescribed for weight loss in some cases and has shown better safety and efficacy profiles when used alone or in specific combinations.
Keep an eye out for part 2, where we discuss the current landscape, incoming treatments and the greatest challenge of weight loss...
