Why Is Weight Loss Sometimes So Difficult? Blame Your Hormones

If there’s one thing everyone can agree on when it comes to weight loss, it’s this: It isn’t easy.

In a survey of more than 3,000 people conducted by Everyday Health, 86 percent of respondents said they were actively trying to lose weight, but half had been unable to commit to one strategy, and 51 percent reported lacking motivation.

Clearly, in spite of greater-than-ever awareness of the problem and countless attempts at solving it, we’re still struggling on both an individual and national level. But maybe instead of questioning why weight loss is so hard, we should be asking why we ever thought it should be easy.

“We have a physiological drive toward weight regain,” says Adrienne Youdim, MD, an adjunct professor of medicine at Cedars-Sinai Medical Center in Los Angeles and the author of Hungry for More. “Even though it’s not their fault, society makes people feel ashamed for regaining weight, to the point that it’s often viewed as a moral failing.”

But now that view is finally changing, in large part because of a new class of drugs that simulate the effects of the hormones that naturally control hunger and fullness, and help regulate body weight. Medications like semaglutide (Ozempic, Wegovy), a glucagon-like peptide 1 (GLP-1) agonist, and tirzepatide (Mounjaro, Zepbound), a GLP-1 and gastric inhibitory peptide (GIP) receptor agonist, have taken the weight loss world by storm because of their dramatic results. Indeed, of those who reported successfully losing weight in our survey, half attributed that success to these kinds of medications.

How Conventional Weight Loss Affects Hormones

Your body produces numerous hormones, which essentially are chemical messengers that control many functions. Under normal circumstances, hormones in your gastrointestinal tract regulate hunger. They convene in the hypothalamus, the area of the brain that’s been shown to control appetite, to determine if you’re hungry or full (satiated).

• Leptin, which tells your body when you’re full
• Ghrelin, which has been dubbed the hunger hormone

As you eat, your gut releases other hormones, such as GLP-1 and peptide YY (PYY). Along with leptin, they tell your brain that food has been received and that it should shut off hunger signals. On the flip side, when your stomach is empty, it releases ghrelin to tell your brain you’re hungry. The longer you go without eating, the more ghrelin will be released, and the hungrier you’ll get, says Robert F. Kushner, MD, a professor in the departments of medicine and medical education at the Northwestern University Feinberg School of Medicine in Chicago.

The trouble is, when you lose weight via calorie restriction, whether through diet, exercise, or both, your body will fight back, trying to regain that weight. “One way it does that is by shifting these hormones in a direction that promotes hunger,” Dr. Youdim says.

For starters, GLP-1 and PYY decrease. So, too, does leptin. Think of leptin as the dipstick in your car that measures your oil, Dr. Kushner says. “Leptin is like having a dipstick in your body fat. Your brain uses leptin to determine if you have enough energy stores or fat in your body to be active,” he says. How much leptin you have is proportional to how much fat you have, which is why people with a higher body mass typically have higher levels of leptin to begin with.

Because your brain never receives the signal that you are full, you end up overeating. In some cases, your body — believing you are not eating enough to feel full — goes into starvation mode and starts to conserve energy so you burn fewer calories, making weight loss even more difficult.

Even if you don't have leptin resistance, anytime you lose fat, you lose leptin. Your brain is being told that because your fat stores are dropping, you have to find food, a survival mechanism genetically engineered into the human body. “Without something automatic like this to tell you to start looking for food, humans wouldn’t have survived as a species,” Kushner says.

At the same time, ghrelin levels rise, making you hungrier. You might be able to handle this at first, but as time passes, you become even less content with what you’re eating, and your hunger grows more intense, Kushner says: “You can’t sustain the amount of ghrelin that’s being released, which makes calorie-restricted diets hard to maintain.”

How Newer Weight Loss Drugs Affect Hormones

One of the reasons why medications known as GLP-1 agonists or dual agonists have been so effective for weight loss is that they counteract the body’s natural responses to increase hunger and promote weight gain. “These drugs mimic naturally occurring gut hormones that control hunger and give them back to individuals in fairly high amounts,” Kushner says. As a result, someone taking one of these medications doesn’t feel hungry, so they’re less likely to overeat.

It’s also been noted that these kinds of drugs dial back what is known as “food noise”: cravings, thoughts, and desires for food that can feel constant and intrusive. “Hunger is mediated by lots of things. Along with being habitual, it can be spiritual or emotional,” Youdim says. “When my patients take these drugs, they tell me they’re able to make sustained changes more effectively without all this noise that gets in the way.”

Each drug uses a different active ingredient to accomplish these tasks. Wegovy and Ozempic contain semaglutide, and Mounjaro and Zepbound have tirzepatide. Another drug, Saxenda, contains liraglutide. The medications all work on receptors for GLP-1, mimicking the effects of that hormone when it comes to appetite and making you feel more full. In biochemistry, anything that causes a response in this way is called an agonist. Drugs that contain tirzepatide are known as dual agonists because they affect receptors for both GLP-1 and GIP.

In addition to helping you feel fuller, GLP-1 agonists slow the rate at which food empties from your stomach, which delays the usual hormonal signals to your brain indicating that you need to eat, says Daniel J. Drucker, MD, a senior scientist at Lunenfeld Tanenbaum Research Institute at Mount Sinai Hospital in Toronto. This twofold effect means you aren’t as hungry in general and may be able to go longer between meals without getting hungry.

Of course, these medications aren’t for everybody. The U.S. Food and Drug Administration (FDA) approved these medications for people with a body mass index (BMI) of 30 or above, which is classified as obesity, or anyone with a BMI of at least 27 and at least one weight-related health issue like diabetes, high blood pressure, or cardiovascular disease. “These drugs are designed to treat medical issues, not cosmetic ones,” Youdim says.

While these new medications have shown enormous potential for treating obesity, experts stress that they are not a cure. They are most effective when used in conjunction with healthy lifestyle habits such as regular exercise, stress management, and a healthy diet, and they have to be taken long term, usually for life.

Everyday Health's Weight Loss Reframed Survey queried 3,144 Americans nationwide ages 18 and older who had tried losing weight in the previous six months. The study was fielded between July 10 and August 18, 2023, across demographic groups, genders, and health conditions. Survey recruitment took place via an online portal, in app, and via email. The margin of error for the sample size of 3,144 is +/-1.7 percent at a 95 percent confidence level.

• Obesity is a widespread problem in the United States, but for decades, treatments focused on lifestyle changes like diet and exercise, which were often ineffective.
• New kinds of weight-loss medications, like Mounjaro and Zepbound, have shed light on how important the role of hormones, including leptin and ghrelin, are to body weight. These drugs, known as GLP-1 agonists, can stimulate the effects of those hormones and help regulate body weight.
• These medications can also quiet what’s known as food noise, which is constant and disruptive thoughts about eating.
• GLP-1 meds aren’t for everyone, and they may cause side effects. It’s also likely you’ll gain the weight once you stop taking them.