Part 1.
From Lizard Spit to Revolutionary New Treatment for Obesity
As a cardiologist, I deal with conditions that lead to heart disease, predominantly high blood pressure, high blood cholesterol, diabetes and obesity. As any doctor will tell you, the hardest of these to treat is obesity.
Of course, the usual approach is to go on a diet, but in reality weight-loss diets don’t work very well. Researchers define a successful diet as one that produces a weight loss of 5 percent. In other words, it’s a success if a 250-pound man loses 12 pounds. Probably what he would really like is to weigh what he did when he graduated from high school—185 pounds, maybe. He would undoubtedly look and feel better. He would also reduce his risk of diabetes, high blood pressure, heart disease and arthritis of his knees, hips and back. Unfortunately, that kind of weight loss from dieting is rare.
There’s hope on the horizon. I’ve been practicing medicine for 50 years, and I’ve never seen anything like this. In 1990, Dr. John Eng, an endocrinologist at the Veterans Administration Center in the Bronx, N.Y., discovered that the saliva of an American lizard know as a Gila Monster contains a hormone that’s almost identical to the human hormone GLP-1 (Glucagon-Like Polypeptide). Scientists had discovered that human GLP-1 lowers blood sugar, suggesting that it might be useful as a medicine for diabetes.
Although chemists could synthesize human GLP-1, it didn’t last long enough in the circulation to be useful a medication. However, Dr. Eng found that Gila Monsters’ GLP-1 lasted longer than human GLP, which made it possible to use as a medication. In 2005, the pharmaceutical company Eli Lilly began marketing a synthetic version of Gila monster GLP-1 under the brand name Byetta for treating diabetes. Doctors jokingly called it lizard spit.
Research trials showed that in addition to lowering blood sugar, exenatide caused some weight loss, an average of 2% of initial body weight. That might not sound like much, but it was notable because most of the diabetes medications at the time made patients gain weight.
Although exenatide lasted longer in the circulation than human GLP-1, it still disappeared quickly, requiring an injection twice a day. Biochemists went to work to develop longer lasting versions of GLP-1. Now there are several GLP-1 medications that remain in the circulation longer than exenatide and are easier to take. For example, liraglutide (brand name Victoza) can be taken once daily. Semaglutide (brand names Ozempic and Wegovy) and terzepatide (brand name Mounjaro) require only one self-administered injection per week.
While all the GLP-1 medications are effective for controlling blood sugar, they differ in the amount of weight loss they produce when used to treat diabetes. Victoza causes an average loss of 6 percent of initial body weight; Ozempic produces a loss of 7 percent.
This brought up the obvious question: If GLP-1 medications help diabetics lose weight, why couldn’t they be used to help folks without diabetes shed pounds? To answer that question, researchers enrolled 1961 overweight volunteers without diabetes to see if the long-lasting GLP-1 medication Ozempic could help them lose weight.
All the participants in the trial were instructed to follow a low calories diet. Two thirds gave themselves a shot of Ozempic once a week. One third got a placebo.
The results were astonishing. In a year and 4 months, the participants who took Ozempic lost 16 percent of their body weight–an average of 34 pounds. Unlike most diets, after which more than half the pounds lost in the first 6 months usually return in a couple years, the weight loss from Ozempic remained until the study ended two years later.
If those results weren’t impressive enough, in 2022 the findings of a study of another GLP-1 diabetes drug, terzepatide (Mounjaro), were published. One weekly shot of Mounjaro produced an average weight loss of 48 pounds–21 percent of initial weight. You read that right: one self-administered shot a week, 48 pounds. No treatment for obesity has ever come close to producing that much weight loss.
This is a game changer. Think of the possibilities: If there were a reliable treatment for obesity, all the medical problems caused by obesity—diabetes, high blood pressure, heart disease, arthritis of the knees and hips—could be reversed or prevented. It would open the door to a world of leisure and work activities for many folks.
The day might come when treating obesity would be like treating high blood pressure. The goal of treatment of high blood pressure is not just to lower it a few points but to get it to a “target” — a pressure that’s low enough to prevent damage to your blood vessels. Similarly, if you have high cholesterol, the goal of treatment is to lower it to a target level where it won’t build up in your arteries. Maybe the time will come when you could treat obesity the same way– choose a desirable weight and keep shedding pounds until you get there.
The amount of fat you carry is controlled by the balance among several hormones, some of which promote fat accumulation, some of which promote fat loss. GLP-1 is a hormone secreted by your intestine that helps prevent you from accumulating too much fat. GLP-1 medications are replicas of natural GLP-1 modified to stay in your system longer. Whereas natural GLP-1 disappears from your bloodstream in a matter of minutes, GLP-1 medications last for as long as a week. This is why semaglutide and terzepetide only need to be taken once a week.
Ozempic comes in prefilled pens. There is no need to draw medicine out of a vial. The needles are smaller and thinner than ones used, for example, for flu shots. The injection is virtually painless.
GLP-1 is a protein, and like the protein in food, if you took it orally your digestive system would break it down to smaller molecules, which would cause it to lose its effectiveness. This is why most GLP-1 medications must be taken by injection. One exception is Rybelsus, a form of Ozempic that is encased in a special capsule that allows it to be absorbed directly into the bloodstream through the lining of your stomach, thereby avoiding digestion in the intestine. At least in diabetics, Rybelsus taken daily causes almost as much weight loss as weekly Ozempic injections do, although it hasn’t been tested in a controlled research trial in people without diabetes.
Rybelsus appeals to folks who are hesitant about giving themselves shots. Because of the unique way in which Rybelsus is absorbed into the bloodstream–through the lining of the stomach rather than the intestine–it must be taken on an empty stomach, and food and beverage must be avoided for 30 minutes afterwards.
GLP-1 medications have been used since 2005 to treat diabetes and have been remarkably free of serious side-effects. You might wonder why these drugs weren’t used earlier to help people without diabetes lose weight. The FDA is especially careful when it comes to approving drugs for weight loss. They knew that if GLP-1 medications really worked for losing weight, a lot of people would want to take them. The FDA considered it particularly important to be sure the medications were safe and effective before allowing them to be prescribed to people who don’t need them for diabetes.
Questions That Remain
It’s only been a few years that GLP-1 medications have used for treating obesity, so longer-range results are unknown. As long as the medication is continued, the weight stays off for at least a couple of years. The question remains whether weight loss is permanent if you keep taking the drug. It’s also unknown whether weight loss can be maintained after stopping the medication.
Among folks who lose weight by dieting, those who are successful at keeping the weight off have one thing in common: they take advantage of being lighter on their feet and more agile to commit themselves to a meaningful exercise routine. Whether the same would apply after stopping GLP-1 medication is unknown.
The most common side-effects of taking GLP-1 are nausea and diarrhea. These can usually be avoided if treatment is started with low doses that are slowly increased. If nausea or diarrhea does occur, it can usually be resolved by temporarily reducing the dose. Studies show that weight loss from GLP-1 medications is not dependent upon their causing nausea.
Serious long term side effects from GLP-1 medication are rare. Indeed, trials show that diabetics who take them on average have fewer heart attacks and live longer than those who don’t. High doses of GLP-1 produce tumors in laboratory animals, but this is true of high doses many drugs. GLP-1 medications have been used for two decades to treat diabetes in humans and have not been shown to cause tumors.
If a Gila Monster bites you, you could end up with an inflamed pancreas–pancreatitits. Initially, doctors worried that GLP-1 medication might similarly cause pancreatitis, but this has not proved to be a problem.
Part 2.
How GLP-1 Medications Work
Remember when you were a kid and your tried to see how long you could hold your breath? It was as easy at first, but after about 30 seconds, respiratory control centers in your brain reacted to falling oxygen levels in your blood and told you in no uncertain terms you needed to breathe. Maybe you thought you could control your breathing better than that, but you really couldn’t. Mother Nature showed you who’s boss
A similar thing happens when you try to reduce the amount you eat. It’s easy at first, but it quickly gets harder. Just as the breathing centers in your brain respond to reduced oxygen in your blood, appetite control centers in your brain sense a lack of food in your system. If you try to eat less, these centers will tell you to eat more. They can also sense when you’ve eaten too much and react by curbing your appetite; at least that’s how it’s supposed to work. However, if you are overweight, those centers are telling you to eat even though you have plenty of calories in your system stored up as fat.
Whether your brain tells you to eat more or eat less is determined by the balance among several hormones, some of which promote weight gain and some of which promote weight loss. An example of a hormone that promotes weight gain ghrelin. If your stomach is empty too long, it secretes Ghrelin into the bloodstream. Ghrelin travels to your brain and stimulates hunger. An example of a hormone that promotes weight loss is leptin, which is secreted by your fat cells. It suppresses appetite. The more fat you have, the more leptin you secrete and the more it should suppress your appetite.
Like leptin, GLP-1s job is to keep you from gaining too much weight. It does this in three ways: It keeps food from being digested too fast. It prevents nutrients in your blood from turning to fat and it calms the hunger centers in your brain.
Calming an Overactive Digestive System
One of the ways the appetite control centers in your brain control your weight is by limiting the amount of food you can put in your stomach. Your stomach acts as sort of a storage bin, or hopper, which regulates how fast food enters your intestine where it is absorbed into the bloodstream. How fast food leaves your stomach is controlled by a muscular ring wrapped around the exit of the stomach, called the pyloric sphincter. When the muscle tightens it constricts the outlet of stomach, which slows the speed with which food leaves the stomach and enters the intestine. This promotes a feeling of fullness, which sends a signal to your brain to stop eating.
Folks who are overweight often digest their food too quickly. Their stomachs empty too fast, so they need more food to make them feel full. They also get hungry sooner after meals. By slowing stomach emptying GLP-1 medications promote more satisfaction with less food and delays the return of hunger after eating.
Keeping Nutrients in the Blood from Turning to Fat
Once in your bloodstream, nutrients are either used to provide energy or are converted to fat by specialized cells called fat cells. Overweight folks turn the nutrients in their bloodstream to fat too rapidly. Their fat cells suck up nutrients too quickly so fewer nutrients reach the brain. Their appetite is harder to satisfy, and hunger returns sooner after eating.
GLP-1 keeps nutrients from being taken up by fat cells too quickly. It does this by reducing the amount of insulin in your blood. One of insulin’s jobs is to transport nutrients in your blood into your fat cells. The amount of insulin you produce is governed by the level of sugar is in your bloodstream. Although most of the sugar in your system comes from eating carbohydrates, your liver produces sugar. It generally doesn’t produce much because there’s usually plenty of carbohydrates in the diet. It may not seem to make sense, but overweight folks’ livers produce more than normal amounts of sugar even though there’s plenty of it in the diet. GLP-1 counteracts that. It reduces the amount of sugar the liver produces. Less sugar means less insulin; less insulin means fewer calories being pushed into your fat cells and more going to your brain to satisfy your hunger.
Calming the Hunger Centers in Your Brain
Ultimately, how much you eat is controlled by centers in your brain. In addition to slowing stomach emptying and reducing the amount of sugar your liver produces, GLP-1 acts directly on these centers to curb your appetite.
Part 3.
Why Drugs May Be the Only Practical Solution
The time-honored approach to losing weight is to go on a diet and get more exercise– calories in calories out. It sounds logical. It is logical. The problem is it usually doesn’t work. You shed a few pounds but almost always gain them back. Even if you manage to lose a little weight, it isn’t as much as you wished.
The American Journal of Clinical Nutrition recently published an analysis of the results of 29 different weight loss programs conducted by teams of professional nutritionists. The programs involved more than a thousand subjects. Dieters consistently lost weight in the first 6 months of the programs but gained most of it back in two years. After five years, average weight loss was 3 percent of initial body weight.
As an example of what a 3 percent weight loss means, it’s not unusual these days for a person who weighs 150 pounds when they graduate from high school to end up weighing 200 at age 50. A three percent weight loss would reduce such a person’s weight to 194 pounds, better than nothing but nowhere near normal.
When you lose weight by dieting, your body fights back. The appetite control centers in your brain act like a thermostat that counteracts changes. Metabolic reactions come into play that increase your desire to eat and slow your metabolism. Invariably, you gain back most of the weight you lost.
As futile as weight loss diets seem to be, we continue torturing ourselves. Approximately 45 million of Americans go on a diet every year, but we keep getting fatter. Half of us are overweight and a third are obese. If as Albert Einstein said the definition of insanity is doing the same thing over and over again expecting a different result, then we’re crazy to keep trying to lose weight by dieting.
People tend to blame obesity on lack of willpower, but that doesn’t make sense. The percentage of Americans who are overweight has doubled in the last 50 years. Why would so many of us lose our willpower? Researchers find no psychological differences between individuals who are overweight and those who aren’t. People with remarkable discipline in other aspects of their life often still have trouble with their weight.
Nobody wants to be fat. It’s not only unattractive, it raises the risk of diabetes; heart disease and stroke, wears out the hips, knees and back, causes infertility in women and reduces testosterone levels in men. Most overweight individuals would do virtually anything to have a healthy body weight.
Another Problem We Blamed on Diet: High Blood Cholesterol
In the 1950’s researchers discovered that high levels of cholesterol in the blood raise the risk of heart attack. Many of our foods contain cholesterol, so some experts assumed, without proof, that high blood cholesterol comes from eating too many cholesterol-containing foods. They figured that if folks could muster up the discipline to stop eating eggs, meat and dairy products, they could reduce their cholesterol level. It sounded logical. Government agencies and medical associations bought into it and started advising Americans to avoid cholesterol-containing foods, but like dieting to lose weight, it didn’t work. Research trials later showed that reducing dietary cholesterol does not prevent heart attacks; it doesn’t even lower blood cholesterol levels.
The level of cholesterol in your blood is not a matter of how much cholesterol you eat; your body makes its own cholesterol. It turns out that the cholesterol in food is difficult to digest. Most of it passes through your intestines and out in your stool. The level of cholesterol in your blood is regulated by your liver, which contains receptors that pull cholesterol out of the blood and excrete it in the stool. Your cholesterol level is determined not by what you eat but by how avidly those receptors remove cholesterol from your blood, and that’s where the problem is.
Scientists have discovered upwards of 1500 genetic variations in the receptors in people’s livers that remove cholesterol from the blood–the human gene pool is full of them. Some cause dangerously high levels of cholesterol; others barely affect it at all. As a result, a large portion of human population–perhaps 30 or 40 percent–have levels of cholesterol in their blood that raise their risk of heart attack–sometimes a lot, sometimes a little, sometimes only when combined with other risk factors such as cigarette smoking, diabetes, high blood pressure or obesity.
Considering that a large portion of the human population have genetically determined cholesterol levels high enough to raise their risk of heart disease, students of evolution might wonder why Mother Nature allowed this to happen. Most dangerous genetic defects disappear from the gene pool by a process of “natural selection—” those who have them don’t live long enough to pass on their genes to the next generation. However, heart attacks usually don’t occur until middle age or later–long after child-bearing years. Cave dwellers lived long enough to pass their genes to the next generation, but rarely long enough to have a heart attack. Only when humans started living longer than 50 years has high blood cholesterol become a significant contributor to mortality,
The good news is that the number of Americans having heart attacks has plummeted in the past two decades, and it’s not because they’re eating less cholesterol. It’s because of technology. In 1973, two American scientists, Michael Brown and Joseph Goldstein, won Nobel prizes for discoveries that led to the development of a type of medication called a statin. One pill a day boosts the cholesterol receptors in the liver, lowers blood cholesterol levels and prevents heart attacks.
If you have high blood cholesterol, it’s not because you eat differently from everybody else. Trying to correct it by avoiding eggs, meat and dairy products won’t work. You can’t change your genes. You’re better off taking medication.
Another Problem We Blame on Diet: High Blood Pressure
Until recently, strokes–damage to the brain caused by blockage of blood vessels—were the third most common cause of death in America. Most strokes are caused by high blood pressure.
For years doctors tried to treat high blood pressure by telling patients to avoid salt. Salt holds fluid in your body. If you don’t have enough salt in your diet, you lose fluid from your blood and your blood pressure falls. Many prehistoric humans died for lack of salt. However, there’s plenty of salt in the modern diet; nobody dies for lack of it. Some people eat so much salt that it raises their blood pressure a little. However, high blood pressure is not caused by eating too much salt. Most folks can eat all the salt they want without it affecting their blood pressure. Blood pressure is determined by genetically programmed reflexes in the kidney that you can’t control by changing your diet.
About 20 percent of the adult population has high blood pressure. Again, you might wonder why Mother Nature allowed this to persist. Like heart attacks, strokes usually occur in middle age or older. Cave dwellers lived long enough to pass on their genes but no long enough to have strokes.
If you have high blood pressure, you might be able to lower it a few points by restricting salt. However, avoiding salt rarely lowers blood pressure enough to prevent strokes. Now we have safe, effective medications that lower blood pressure and prevents strokes. One or two pills a day will usually lower it to a safe level.
Thanks to blood pressure medication, the incidence of strokes in the United States has plummeted. It makes little sense to keep trying to treat high blood pressure by reducing your salt intake. You’re better off taking medication.
How Changeable Is Our Lifestyle?
Trying to lose weight by eating less doesn’t work for the same reason low cholesterol and low salt diets don’t work. Our weight, like our cholesterol and blood pressure levels, is controlled by things that are difficult to change; only in this case it’s not our genes that’s causing the problem, it’s our lifestyle.
While it’s true that some people are genetically more prone than others to weight gain, obesity was uncommon until the last 100 years. Genes don’t change that fast. Something we’re doing or not doing is making us fat, and it’s proving to be almost as difficult to change as our genes.
The key to understanding what it is about our lifestyle that’s making so many of us fat lies in understanding what’s causing another modern-day epidemic, type 2 diabetes.
The Connection between Obesity and Type 2 Diabetes
The pancreas, a gland located in your upper abdomen, produces the hormone insulin. Insulin opens gates on the surface of cells to allow glucose to pass out of the bloodstream and into cells. If you don’t make enough insulin, or notably if your cells don’t respond normally to insulin–if they become “insulin resistant” —glucose builds up in your blood, which is what we call type 2 diabetes.
To understand the connection between obesity and type 2 diabetes, you first need to know the difference between type 1 diabetes and type 2 diabetes. Type 1 diabetes is caused by autoimmune damage to the insulin-producing cells in the pancreas, which results in insulin deficiency—simple enough. Type 2 diabetes is not so simple. Patients with type 2 diabetes make plenty of insulin. The problem is their body loses responsiveness to it—they become “insulin resistant.” Consequently, they have to produce as much as five times the normal amounts of insulin to control the level of glucose in their blood. Their blood sugar may rise a little but their insulin levels skyrocket. So in addition to the effects of high blood sugar, type 2 diabetics must deal with the effects of abnormally high insulin levels, which often cause more problems than high blood sugar, and one those problems is obesity.
The percentage of people who have Type 1 diabetes has not changed since the 1800s. In contrast, the incidence of type 2 diabetes has skyrocketed.
Excess insulin secretion goes on for years before the blood sugar level rises and doctors diagnose type 2 diabetes. At first the insulin producing cells can keep up with demand, and blood sugar levels remain near normal. However, years of insulin overproduction eventually wear out the insulin producing cells. When production can no longer keep up with demand, blood sugar rises. You might still make plenty insulin, just not enough to keep your blood sugar down.
Not everyone with insulin resistance goes on to develops diabetes. In fact, most don’t. Even though they produce more-than-normal amounts of insulin, their insulin- producing cells keep up with demand. The problem is that high insulin levels keep shunting nutrients out of the bloodstream and into fat, which is why the number of people with obesity has risen along with that of type 2 diabetes.
The Underlying Epidemic: Insulin Resistance
You need insulin to metabolize carbohydrates. If you ate as little carbohydrate as your cave dwelling ancestors did, you wouldn’t have to worry about type 2 diabetes or obesity. Indeed, cutting carbohydrates in the diet helps treat type 2 diabetes. But there’s another problem besides carbohydrates at work here. The amount of insulin your body produces is not only dependent on how much carbohydrate you eat but also on how responsive your muscles are to insulin.
Your muscles are the body’s main consumers of carbohydrate and the target of most of the insulin you produce. If they lose responsiveness to insulin–if they become “insulin resistant,” your pancreas has to secrete more than normal amounts of insulin to control your sugar glucose levels. The reason so many of us these days are overweight and diabetic is that we are being hit by a double whammy: we consume too many carbohydrates—at least compared to cave dwellers–and our muscles lose responsiveness to insulin.
Unlike high blood cholesterol and high blood pressure, which are caused by genetically determined factors we can’t change, insulin production is under our control–in theory. By reducing the amount of carbohydrates in our diet and increasing our muscles’ responsiveness to insulin with exercise, we could reduce the amount of insulin we produce, stop wearing out our insulin producing cells and quit forcing calories into fat. The problem is two realities of modern life that are changeable in theory but in reality prove to be immutable. As hard as we try, we can’t seem to avoid carbohydrates enough and keep our muscles responsive to insulin enough to avoid gaining weight and putting ourselves at risk of type 2 diabetes.
We modern humans consume hundreds of times more carbohydrates than our prehistoric ancestors did because we rely on refined carbohydrates, such as flour, potatoes, rice and sugar, to provide a major portion of our calories. The problem is that as soon as refined carbohydrate arrive in the intestinal tract they turn to pure sugar. Our prehistoric ancestors didn’t have to worry about this; there were no refined carbohydrates in their diet. Cave dwellers had no way to process grains or refine sugar. The carbohydrate they consumed—wild fruit, roots, bark and grasses–contained plenty of vitamins, minerals and fiber but yielded little in the way of calories. They got most of their calories from meat, fish and bugs.
However, folks in the 1800’s ate plenty of bread, potatoes, rice and sugar. They didn’t gain weight and develop type 2 diabetes because they were more physically active than we are now. Cars and busses hadn’t been invented. People had to walk several miles a day to tend to their needs and spent most of their days doing physical work. Now we rely on cars, busses and trains get around, and most of us work at sedentary occupations. It’s no coincidence that America’s epidemic of obesity and diabetes began around 1915 when Henry Ford started mass producing automobiles. We have built a society around motorized transportation.
Refined carbohydrates are one part of the double whammy that’s making us fat and diabetic, motorized transportation is the other part. The question is what can we do about it? If the answer is not much, then like high blood cholesterol and high blood pressure, we may end up relying on medication. We now have excellent medicines for treating high blood cholesterol and high blood pressure. The treatment of these conditions has caused deaths from heart attack and stroke to plummet. Until recently there were no medications available that could reliably reverse obesity, but now may be a new day.
Ozempic and Mounjaro counteracts the effects of insulin resistance by reducing the amount of insulin the body has to produce to deal with the relatively excessive carbohydrates in our diet compared with that of prehistoric humans and with our relatively low physical activity levels compared with that of our 19th century ancestors.
Part 4. The Big Question
There’s no doubt that the GLP drugs Ozempic and Mounjaro can make you lose a lot of weight and that the weight loss persists for at least 2 years, which is how long the research trials have lasted. The big question is how long will weight loss persist after 2 years.
Best-Case Scenario
The best-case scenario would be that you could take the medication until you reach a desirable weight, stop it and the weight would stay off. Research shows that if you discontinue the medication after a few months and make no other changes, you will probably regain most of the weight you lost. The same thing happens when you lose weight by dieting. If you go back to eating normally and make no other changes, you usually regained the weight you lost.
The body behaves as if it has a set-point that governs your body weight. If your weight falls below this set-point, your body fights back and tries to regain the weight you lost. Your metabolism slows down and your appetite increases, making you eat more than you burn off. Folks who lose weight by dieting usually regain about half the weight they lost within a year.
However, there are important exceptions to this generalization: A minority of dieters succeed in losing a lot of weight and keeping it off. Studies show that people who lose more than 10 percent of their body weight and keep it off for years have one thing in common: they walk or run for exercise, and they do it a lot–the equivalent of an hour a day of walking or a half hour of running.
One of the problems with being overweight is that it makes weight bearing exercise harder. It stresses your muscles, reduces your endurance and causes your joints to ache. The unpleasantness associated with weight bearing activity sets up a vicious cycle: the more weight you gain, the less walking or running you want to do; and the less walking or running you do, the more weight you gain.
The good news is that the opposite is true. When you lose weight, it’s easier to exercise, which promotes more weight loss. If you use the weight you lose from taking a GLP-1 medication as a “bridge” to a vigorous walking or running routine, you may be able to keep the weight off even if you stop the medication.
Next-Best-Case Scenario
The next best scenario resulting would be that, while you might not be able to stop the medication, the weight would stay off as long as you keep taking it. In research trials, weight loss from Ozempic and Mounjaro lasted until the studies ended after 2 years. To date there are no published studies on the results after 2 years.
Some specialists have expressed the opinion that the drugs will probably need to be taken for life. Obesity causes long lasting changes in the body that make it difficult to maintain weight loss. When you gain a lot of weight, fat builds up in places it normally wouldn’t be, including muscle cells. Fat in the muscle cells makes them resistant to the effects of insulin. Consequently, the pancreas then has to produce more than normal amounts of insulin to control the blood sugar, and excess insulin makes you gain weight. The fat in muscle cells doesn’t go away immediately upon losing weight; it sticks around for months, which makes you tend to regain the weight you lost.
However, research shows that if weight loss is maintained long enough, muscle cells eventually regain their sensitivity to insulin. If weight loss can be maintained for several years, especially if it is used as a bridge to exercise, it is possible that medication will no longer be needed. Of course, if you stopped the medication and started regaining weight, you could always go back to taking it again.
Worst-Case Scenario
A less attractive outcome would be that the medication would stop working after a couple years and you would regain the weight you lost even if you kept taking it. While many medications continue to work as long as you keep taking them, the body develops a “tolerance” to others, which causes them to lose their effectiveness over time. Tolerance can often be overcome by increasing the dose of the medication. However, it is possible that if taken long enough these drugs could lose their effectiveness altogether.
Currently there are no published data on the effectiveness of GLP-1 medication for maintaining weight loss beyond 2 years. A hopeful sign is that the effectiveness of GLP-1 drugs for treating diabetes–not necessarily for obesity–continues as long as the medication is taken.
TO BE CONTINUED
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