The History of Obesity Treatments

The History of Obesity Treatments

The current discourse on obesity in the media can easily cause people to think that this is a new epidemic, only dating back a few decades. Accordingly, there are many programs tailored to weight loss. And yet, the unearthing of miniature obese female statuettes indicates that obesity has been around for over 30,000 years, specifically, the Venus of Willendorf and the Venus of Hohle Fels. 

We have evidence that obesity continued to be an issue, even if at the time it was the exception rather than the rule. In ancient Egypt, studies of reconstructed skin folds of royal mummies indicate that some were obese. Around 500 BCE, the Indian physician Sushruta described the condition (‘Madhu-meta’) as imparting a smell and taste similar to honey in patients, and he associated the disease with a congenital defect or a faulty diet, with symptoms including obesity and increased soporific tendency (now known as type 1 and type 2 diabetes), amongst others. He recommended physical work, fasting, exercise, and depletory measures to combat the disease.

Awareness of the dangers of obesity extended to the ancient Greeks, with Hippocrates (460-377 BCE) noting that overweight people often died earlier than those who were lean. Roman physician Galen (129-200 CE) made reference to polysarkos (morbidly obese) individuals, who could not ‘walk without sweating, cannot reach when sitting  at the table because of the mass of his stomach… cannot clean himself.’ He attributed the cause of obesity to ‘bad humors.’ Physicians during this time made recommendations such as limiting food and drink intake, as well as exercise. Physicians during this time also recommended emetics (such as hellebore plants and honey water) and cathartics (such as juice of bindweed, Cnidian berry, and sea spurge). In essence, these were the first weight loss drugs.

During medieval times, gluttony was considered one of the ‘seven deadly sins’ of the Catholic Church, while simultaneously being a sign of wealth. Awareness of the issues surrounding obesity extended to the Islamic Empires of Central and Southwest Asia, with Avicenna (a prominent figure in the Arabic medical tradition) describing the ‘sweet taste of diabetic urine’ in his 12th-century encyclopedia.

The 18th and 19th centuries in Europe saw a change in perception of the disease, with physicians recommending lifestyle changes including exercise, fresh air, and an abundance of vegetables by Scottish physician George Cheyne and limiting carbohydrates and eating more protein by Army physician John Rollo and Royal undertaker William Banting. 

Fast forward to the 20th century, and the desirability of being skinny came to the forefront. Furthermore, the medical need for keeping people at a certain weight caused doctors to begin recording patients’ height and weight during visits. Some companies tried taking advantage of the situation by marketing products such as Human Ease, which they claimed would not only treat obesity but all other maladies… only for it to later be discovered as consisting of 95% lard. 

In the 1920s doctors began prescribing thyroid medications to healthy individuals as a way to help them lose weight. In 1933 doctors began prescribing 2-4 dinitrophenol (DNP), which caused weight loss by decoupling oxidative phosphorylation, which lead to both higher metabolic rates and a higher fat metabolism in patients. However, by 1938 its use stopped due to the drug’s toxic hypothermic effects. Laxatives were also used in the 1930s as a way to combat excess weight.

The 1940s saw the rise of amphetamines as a means to achieve weight loss. The mechanism by which amphetamines cause weight loss is through the release of norepinephrine, along with some dopamine and serotonin, thereby increasing activity in the central nervous system (CNS) along with resting energy expenditure. In conjunction, these factors lead to a decrease in appetite, leading to a general decrease in calorie intake and weight loss. Several varieties of these drugs were released between 1945 and 1962, with modifications to make them less addicting by varying their dopamine and serotonin receptor specificities, including phenmetrazine (1956), bydiethylpropion, benzphetamine, and phendimetrazine (all in 1959). Another innovation during the 1950s was to combine the aforementioned drugs with a barbiturate in order to reduce the agitation that is often associated with amphetamine use. 1959 also saw the release of phentermine, which causes dopamine and serotonin neurotransmitter release (to a lesser extent than norepinephrine release), thus working to reduce weight while having less addictive properties. The drug is still in use today in the USA for short-term treatment of obesity. 

The Kefauver-Harris Amendment to the US Food, Drug, and Cosmetic Act was passed in Congress in 1962 and required substantial evidence of efficacy for all new drugs while simultaneously subjecting all existing drugs to the Drug Efficacy Study and categorized them by their levels of effectivity. As such, it was only in 1973 that three amphetamine-based weight-loss drugs were approved (fenfluramine, chlorphentermine, and mazindol). However, by 1977 all three drugs were restricted to short-term use only (a few weeks) due to concerns over their addictive potential. In the following years, the use of amphetamine-based weight loss drugs declined, until 1992 trials showed that the combination of fenfluramine and phentermine in low doses established weight loss of up to 15.9% from baseline with no major adverse effect over a 34-week period (and a follow-up period of up to 4 years treatment), thus giving rise to the Phen-Fen era. New FDA guidelines for weight-loss drugs were released in the mid-1990s, while new regulations were also released in Europe. This brought about the approval of dexfenfluramine (an isomer of fenfluramine) in 1996, on the condition that the subject has a body mass index (BMI) of over 30 or at least 27 accompanied by a condition such as hypertension, type 2 diabetes, or dyslipidemia (due to concerns of neurotoxicity from animal studies and primary pulmonary hypertension in human epidemiological studies). Initially widely prescribed, the approval for the drug was quickly withdrawn following a flurry of left-sided heart degeneration in patients who had used the drug. Furthermore, the publication of an article detailing the increased risk of valvular heart disease stemming from the use of both dexfenfluramine and fenfluramine brought about a litany of lawsuits leading to a $14 billion settlement. For its part, phentermine was not withdrawn from the market and is still used for short-term weight loss in some countries including the USA and the UK (long-term use necessitates that it is used in conjunction with other drugs). In 1997 Sibutramine (an amphetamine derivative) was approved in the US and Canada, with Europe following step in 1999. As opposed to previous amphetamine-based drugs, it acts as a sympathomimetic, thus blocking any neuronal uptake of any released serotonin and norepinephrine, inducing feelings of satiety. Unfortunately, users began to experience heightened blood pressure and heart rate, and overall safety concerns (from further studies) led to the withdrawal of the drug from the markets in the USA, Canada, and Europe in 2010.

Beyond amphetamine-based drugs, other weight loss drugs came into circulation starting with orlistat (still in circulation today) in the late 1990s. It inhibits pancreatic lipase, which then leads to a reduction in digestion and absorption of fats from the small intestine by up to 30%. Unfortunately, studies showed that it only leads to a mean reduction of 2.9 kilograms over a 4-year period, with gastrointestinal side effects making long-term use difficult. Another drug that went into use in 2006 in Europe was rimonabant, which works as an inverse agonist on cannabinoid receptor CB1 and thus reduces appetite. Unfortunately, there were psychiatric risks associated with its use, which led to it never being approved for use in the USA, and its withdrawal from everywhere else by 2008. 

Other drugs that are currently in use are lorcaserin (which causes the release of serotonin and inhibits the subsequent uptake of serotonin – not approved for use in Europe due to a low benefit-to-risk ratio), phentermine (administered in combination with extended-release topiramate – exact mechanism unknown, not approved for use in Europe due to the lack of long-term studies on heart and blood vessels, along with psychiatric effects), and naltrexone/bupropion (induces weight loss through appetite suppression and increased energy expenditure – currently approved pending further research).

In recent years, a new class of drugs has come to the forefront of obesity treatments (with certain prerequisites, such as having a certain BMI or other conditions). In essence, they are GLP-1 agonists, mimicking a hormone that regulates the appetite and feeding centers in the brain. Furthermore, they have shown significantly fewer side effects than previous drugs. They are Saxenda (liraglutide), which has been shown to reduce overall body weight by 5%, and Wegovy (semaglutide – what can it do for you?), which has been shown to reduce overall body weight by a whopping 15%. A weekly injection, it works quickly, regardless of which program one chooses. You can buy semaglutide here. Furthermore, a new drug called tirzepatide, which also imitates a second hormone called GIP (which might improve how the body breaks down sugar and fat), is in the process of trying to obtain FDA approval.  

Beyond the weight loss drugs described above, bariatric surgery (also known as weight loss surgery) is another option that has been available to those suffering from obesity. Intended for those who have not been able to lose weight through other means, the surgery makes changes to one’s digestive system. There are a few different options, the most common of which are as follows: 

  1. A gastric sleeve, whereby the surgeon removes most of the stomach, only leaving a banana-shaped section that is closed with staples. As the stomach can now only fit a much smaller amount of food, the patient is full sooner. Irreversible, the surgery may cause hormonal changes, along with changes to the bacteria in the gastrointestinal system affecting metabolism and appetite. 
  2. Gastric-bypass surgery (also known as Roux-en-Y gastric bypass), involves three steps: stapling the upper part of the stomach to create a small pouch, dividing the small intestine into two parts, attaching the lower part to the stomach pouch (allowing food to bypass most of the stomach, so the body absorbs fewer calories), and finally reconnecting the upper part of of the lower intestine to another part of the small intestine located further down. Thus, gastric juices can flow from the bypassed part of the lower intestine to the lower part of the lower intestine, allowing the food to be fully digested. Much like the gastric sleeve, a bypass surgery affects hormones, bacteria, and other substances in the gastrointestinal tract affecting metabolism and appetite. While difficult to reverse, the bypass is reversible if deemed medically necessary.
  3. An adjustable gastric band involves the creation of a small pouch in the upper part of the stomach through the placement of a ring with an inner inflatable band around the top of the patient’s stomach. The inner band has a circular balloon within it filled with a saline solution, and the band can be adjusted through the injection or removal of the saline solution through a port that is placed under the patient’s skin. Much like the first two options, the band induces weight loss by limiting the food a patient can eat prior to feeling full. However, it is less commonly performed as it has been found to be less effective while also causing more complications (which usually involve the need for the removal of the band due to intolerance).

Weight loss surgeries hold the potential for serious side effects. These include bleeding, infection, leaking from the sections of the parts of the stomach where it is stapled or sown together, blood clots in the legs (that can move to the lungs or heart), and diarrhea. Moreover, in some rare cases, surgery-related issues can lead to death. There is also the potential for other later-occurring side effects, such as the body not getting enough nutrients (leading to issues such as anemia and osteoporosis), gallstones, and other issues with the gastric bands. As such, candidates for this surgery should have a BMI of 40 or more or a BMI of 35 in conjunction with a serious health problem linked to obesity, such as type 2 diabetes. Other candidates include those with a BMI of 25 with type 2 diabetes which is difficult to control with medical treatments and lifestyle changes.

The need to maintain a healthy weight has been an issue for thousands of years, and that continues to be the case today. Classified by the American Medical Association as a disease since 2013 (rather than a risk factor for other diseases), doctors are now able to make treatments directly related to obesity. And although the issue does not appear to be going away anytime soon, its prominence in the public discourse and modern treatments gives hope that those suffering from it will soon be better able to get it under control.