by Carol A Westbrook
What is the hardest thing about dieting, the reason that most dieters give up? They get hungry.
Wouldn’t it be great if there were a pill that would leave you satisfied after a diet meal without those hunger pangs? A medicine that would keep you on a diet and help you lose the weight you need to lose? Well, these medications are no longer a dream—they now exist. These are the GLP-1 drugs. These drugs are a potential lifesaver for people who are overweight or obese.
Why do we care about these GLP-1 drugs? Because we are fat. We hate being fat. And fat can be fatal. Four million people die each year as a result of obesity.
How fat are we? Almost three-quarters of adults in the US are overweight, including 40% who are frankly obese. [See note at end for definition of BMI, and how it relates to obese and overweight]. This epidemic of obesity is not just restricted to adults, According to the Centers for Disease Control and Prevention (CDC), about 20% of children and adolescents aged 2-19 were obese in 2018. It’s not a toddler’s fault that he is overweight. There must be something inherently wrong with our lifestyle that makes even innocent children eat too much food—or the wrong food.
It wasn’t always this way. Thinking back to my childhood in the 60’s, it was rare to have an obese child in the classroom who, sadly, became the butt of many jokes. Now, overweight is accepted as normal, in both children and in adults. Ancient paintings, tapestries and even Egyptian tomb carvings showed that throughout history and until recently, people maintained a normal weight, balancing their food intake with their needs. But during my lifetime there has been a major disruption of this equilibrium so that the balance has shifted and weight gain has become the norm. The worldwide obesity rate has nearly doubled since 1980. What has changed?
For most of the time that humans were on the earth, constancy of weight is the result of a rather complex metabolism which evolved over eons to support a variety of foraged plants, nuts, berries, tubers, and so on. Meat found its way into the human diet over 2 million years ago while our tree-dwelling ancestors subsisted on fruits and nuts. Later, cooked meat and plants appeared about 800,000 years ago, and the only major change in the diet—until recently– came about 25,000 years ago with the appearance of bread. Milk and dairy were not consistently eaten.
Human metabolism has evolved to deal with this variety of food, consuming enough to meet energy and nutritional needs and stopping when these needs are met. This steady-state is regulated by an extensive network of hormones and small peptides. For example, the consumption of glucose, a sugar, triggers the release of insulin, which is required to metabolize the sugar; insulin causes the release of glucagon which suppresses insulin release and suppresses appetite, and consumption stops. Fat stores are regulated in part by a peptide called leptin, which signals the brain about hunger and satiety, maintaining weight and energy balance. We are only now beginning to understand the complexity of these metabolic pathways. But it is becoming clear that what worked for our ancestors is no longer adequate for modern man, whose digestion is the same as prehistoric man, but his diet is not.
This dietary change is probably the result of World War II. For the US to enter the war meant growing, processing and shipping enough food to feed millions of uniformed personnel. Each day troops require 4,000 to 6,000 calories, which they must procure on location or bring along. The military made a concerted effort, in collaboration with university labs, packing plants, canneries, packaging companies, fruit farms, and hatcheries, to develop new food processing techniques and products.
Many products resulted from this effort including those that were easier to cook, lightweight, stayed fresh longer, and substituted modified ingredients so they were less expensive to produce. An estimated half of the items in a typical grocery store can trace their origins or success to the military’s influence. Supported by nutritionists, chemists, bacteriologists, and other advisers, the Quartermaster Corps worked with industry on designing packaging, consulted with the surgeon general on what to include or avoid in rations, took delivery of the components and assembled the ration packages. This food provisioning effort work has been compared to the Manhattan project, as it was invisible to the citizenry, was carried out in a large number university labs, packing plants, canneries, fruit farms and so on, and introduced new food processing techniques and products to the market at a fast clip.
Among other items, military-funded research produced includes dry yeast, frozen concentrated orange juice, M&M’s, refined cake mixes, enriched flours, freeze-dried fruits. Powdered dehydrated cheese—which was easier to ship—was developed. The success of Cheeto snack foods made from this powdered cheese inspired any number of products that soon flooded the market. Frozen pre-cooked foods led to the development of TV dinners in 1953, which continue to be a supermarket staple.
These actions profoundly changed how the entire nation eats. Within a lifetime, humankind was facing a diet consisting of delicious substances that they had not previously encountered without the metabolic ability to regulate their intake. For example, take cake frosting.
The ingredients label on a can of Betty Crocker vanilla frosting reads: sugar, high fructose corn syrup, palm oil, corn starch, salt, monoglycerides, polysorbate 60, sodium stearoyl lactylate, sodium acid pyrophosphate, natural and artificial flavor, yellows 5 & 6, citric acid, potassium sorbate.My homemade frosting contains: powdered sugar, butter, vanilla.
Perhaps the largest change came with the introduction of high fructose corn syrup, HFCS. In the 1970’s, the high cost of import sugar and the low cost of corn due to farm subsidies made it more economical to use HFCS made from American corn as a sweetener,. Cheaper and sweeter than sugar, this product has found its way into sugary treats (such as ice cream, soft drinks, cakes and candy), as well as most condiments, from ketchup to salad dressing. HFCS is felt to be responsible for much of the obesity in the US—especially because of its presence in soft drinks. Unlike glucose and sucrose, HFCS does not stimulate the release of insulin, and thereby loses the appetite suppressant power of sugar-sweetened drinks.
Research into these metabolic pathways that result in obesity has led to at least one drug which might help to control the current obesity epidemic. These are known as GLP-1 agonists, which were found while developing a cure for diabetes. Diabetes, if you recall, is a disease in which the body does not produce enough insulin for its needs. Insulin is needed to transport glucose into cells, where it is the main fuel that keeps cells alive and functioning; insulin also reduces the level of sugar in the blood, thereby avoiding the complications of high glucose (glycemia) such as retinal bleeding, infections, atherosclerosis, heart disease and stroke. In Type 1 diabetes mellitus (DM) the body is incapable of producing any insulin at all, and thus, the only treatment is insulin. In Type 2 DM, the body makes insulin but not enough for its needs. Type 2 DM is acquired in older individuals, and generally accompanies obesity; it is treated with agents that stimulate the body to release more insulin.
Insulin was discovered in 1921, and proved to be an effective treatment for DM, which woud otherwise be a fatal disease. glucagon was discovered in 1923. Its role appeared to be as a counter-regulatory hormone to insulin, opposing insulin action by keeping blood sugar from dropping too low, which potentially damages the brain and could lead to death. Thus insulin and glucagon act in harmony to balance the body’s blood sugar needs.
In 1986 Sixty-five years after glucagon’s discovery, two closely-related peptides (small proteins) were identified in the DNA surrounding glucacon; these were designated GLP-1 and GLP-2 (glucagon-like peptide -1 and -2) by Habener, at the Massassusetts General Hosopital. These peptides were found to stimulate the release of insulin and the suppression of glucagon, and as such seemed that they might be effective treatment for Type 2DM. By 2005, Byetta became the first GLP-1 approved by the FDA for the treatment of type 2 diabetes. Modified forms of these peptides with fewer side effects were developed, and Lotte Knudsen from Copenhagen tested their activity in a clinical setting, and they were found to be effective treatments for type 2 DM..
While GLP- was in trial for diabetes, a remarkable fact came to light: researchers observed that many patients experienced significant weight loss. Further study revealed that this weight loss is independent of whether or not the treated subject had diabetes.
Pharmaceutical companies were quick to capitalize on this discovery. With many variants produced to treat obesity. The 2024 Lasker-DeBakey Clinical Medical Research Award recognized Joel Habener Svetlana Mosjov and Lotte Bjere Knudsen for their discoveyry and develeopmenet of GLP-1 receptor agonists, medicines that have revolutionized the treatment of obesity.
The rise of GLP-1s has been meteoric. Between 2018 and 2023, prescriptions for these drugs increased by a staggering 300%. Their effectiveness, relative safety compared to previous medications and convenience have propelled them to the forefront of the weight loss treatment landscape. These are the first of many drugs that may be developed to help modern man fight the unhealthiness of the modern diet.
Returning to a more natural diet might be the best way to maintain a safe weight, but realistically it will be difficult or expensive for the entire population to do this. Perhaps in the future it might be easier to treat obesity with drugs when it occurs, as new drugs are invented that might tweak our metabolism to help fight the effects of processed food.
NOTE.
Overweight and obese ae defined in reference to an individual’s BMI, of Body Mass Index.
- overweight is a BMI greater than or equal to 25
- obesity is a BMI greater than or equal to 30
Using weight in kilograms (kg)) and height in meters (m), BMI is calculated by dividing weight in kg by height in meters squared (m2).
BMI = weight (kg) / Height (m2)