Scientists define a successful diet deserving of publication in a medical journal as one that produces a weight loss of 5 percent. In other words, it’s deemed a success if a 250-pound man loses 12 pounds. Such a guy might wish he could weigh what he did when he graduated from high school, 190 pounds maybe, which would be a 24% reduction. He would undoubtedly look better 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 alone is unusual.
Now there’s a more effective way to lose weight. In 1990, Dr. John Eng, a chemist who studied reptiles, discovered that the saliva of a certain kind of lizard called a Gila Monster contains a hormone that is almost identical to the human hormone GLP-1 (Glucagon-Like Polypeptide).
Scientists had known for years that human GLP-1 lowers blood sugar and wondered if the hormone could be useful for treating diabetes. The problem was that it didn’t last long enough in the circulation to be useful as a medicine for diabetes. 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, pharmaceutical company Eli Lilly began marketing a synthetic version of lizard GLP-1 under the brand name Byetta. (Doctors jokingly call it lizard spit, although it doesn’t really come from lizards; it’s manufactured in chemistry labs.)
It turned out that in addition to lowering blood sugar, exenatide caused some weight loss, an average of 2%. That might not seem like much, but it was notable at the time because most of the diabetes medications available at the time made you gain weight.
Although exenatide lasted longer in the circulation than human GLP-1, it still required two injections a day to be effective. Biochemists soon developed longer lasting versions of GLP-1 drugs. Now there are several GLP-1 drugs that are easier to take. For example, liraglutide (brand name Victoza) can be taken once daily. Semaglutide (brand names Ozempic and Wegovy) and terzepatide (brand names Mounjaro and Zepbound) which 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. In diabetics, Victoza causes an average loss of 6 percent of initial body weight; Ozempic produces a loss of 7 percent. But remember, that’s in diabetics. What about people who don’t have diabetes but just want to lose weight?
This brought up the obvious question: If GLP-1 medications help diabetics lose weight, why couldn’t they be used to help people without diabetes shed pounds? To answer that question, researchers studied two thousand overweight volunteers without diabetes to see if the long-lasting GLP-1 Ozempic could help them lose weight too. Two thirds of the participants gave themselves an injection of Ozempic once a week. One third took a placebo shot.
The results were astonishing. In a year and 4 months, the participants who took once weekly 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 was is a game changer. A cure for obesity could reverse or prevent all the medical problems caused by being overweight, including type 2 diabetes, high blood pressure, heart disease and arthritis of the knees and hips. For many people, it would open the door to a world of work and leisure activities difficult for them before and alleviate the embarrassment and self-esteem issues often associated with obesity.
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.
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.
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 them causing nausea.
Serious long term side effects from GLP-1 medications are rare. Indeed, trials show that diabetics who take them on average have fewer heart attacks and live longer than those who don’t. Ultra-high doses produce tumors in laboratory animals, but this is true of many drugs. GLP-1 medications have been used for two decades to treat diabetes in humans and have not been shown to cause tumors.
