Everything You Need to Know

If you live in a larger body, sometimes it feels like you can’t win.

If you don’t lose weight, people will criticize you for being “lazy,” “unhealthy,” or “lacking willpower.”

But if you take medication to help you, you’ll be criticized for “cheating” or “taking the easy way out,” even if you’ve tried for decades to manage your weight through diet, exercise, and lifestyle changes (sometimes extreme ones).

In this article, we’ll be talking about a highly contentious group of medicines—GLP-1 receptor agonist drugs such as semaglutide (Ozempic, Wegovy, Rybelsus) or tirzepatide (Mounjaro, Zepbound).

And people have lots of opinions about them.

But the opinion that matters most? Yours.

At PN, we’re medication agnostic.

We’re not here to judge whether a person should or should not take medication for weight loss. Ultimately, that’s a choice left up to you, with the guidance of your primary care physician.

Either way, we’re here to support our clients and elevate their results.

Whether you take medication or not, a coach can help you optimize nutrition and satiety with the right foods, find exercises that work with your changing body, and help you navigate the emotional ups and downs that come when you attempt to tackle a big, meaningful, long-term goal.

However, we also understand that if you’re debating the pros and cons of beginning (or continuing) medication, you might have mixed feelings.

If you’re not sure if these new medicines are right for you, we have your back. In the following article, we’ll give you the honest, science-backed information you need to make a confident decision.

You’ll learn…

• Why it’s so hard to lose (and keep off) fat
• Why taking medication isn’t “cheating,” nor is it the “easy way out”
• How GLP-1 drugs work, and the health benefits they can have (aside from weight loss)
• How to determine if you’re at a “healthy weight” (it’s not just about BMI)
• What actions you can take to minimize side effects and maximize long-term health, if you do decide to take these medications

Let’s begin.

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First, why is it so hard to lose fat?

Fat loss is hard. Period.

But for some people, it’s harder still—because of environmental, genetic, physiological, social, cultural, and/or behavioral factors that work against them.

Here are a few of the contributing factors that can make fat loss so challenging.

We live in an environment that encourages a caloric surplus.

Imagine life 150 years ago, before cars and public transit were invented. To get from point A to point B, you had to walk, pedal a bicycle, or ride a horse.

Food was often in short supply, too. You had to expend calories to get it, and meals would just satisfy you (but not leave you “full”).

Today, however…

“We live in an obesogenic environment that’s filled with cheap, highly-palatable, energy-dense foods [that make overeating calories easy, often unconsciously],” says Karl Nadolsky, MD, an endocrinologist and weight loss specialist at Holland Hospital and co-host of the Docs Who Lift podcast.

“We also have countless conveniences that reduce our physical activity.”

Of course, even in such an environment, we have people in lean bodies, just as we have people who struggle to stop the scale from continuously creeping up.

Why?

Genetically, some people are more predisposed to obesity.

Some genes can lead to severe obesity at a very early age. However, those are pretty rare.

Much more common is polygenic obesity—when two or more genes work together to predispose you to weight gain, especially when you’re exposed to the obesogenic environment mentioned earlier.

People who inherit one or more of these so-called obesity genes tend to have particularly persistent “I’m hungry” and “I’m not full yet” signals, says Dr. Nadolsky.

Obesity genes also seem to cause some people to experience what’s colloquially known as “food noise.”

They feel obsessed with food, continually thinking, “What am I going to eat next? When is my next meal? Can I eat now?”

Physiologically, bodies tend to resist fat loss.

If you gain a lot of fat, the hormones in your gut, fat cells, and brain can change how you experience hunger and fullness.

“It’s like a thermostat in a house, but now it’s broken,” says Dr. Nadolsky. “So when people cut calories and weight goes down, these physiologic factors work against them.”

After losing weight, your gut may continually send out the “I’m hungry” signal, even if you’ve recently eaten, and even if you have more than enough body fat to serve as a calorie reserve. It also might take more food for you to feel full than, say, someone else who’s never been at a higher weight.

Being in a larger body often means being the recipient of fat stigma and discriminatory treatment.

Until you’ve lived in a larger body, it’s hard to believe how different the world might treat you.

Our clients have told us stories about being bullied at the gym, openly judged or lectured at the grocery store, and otherwise being subjected to innumerable comments and assumptions about their body shape, health, and even worth.

Even in medical settings, people with obesity are more likely to receive poor treatment.^{1, 2} Healthcare providers may overlook or downplay symptoms, attributing health concerns solely to weight. This can lead to delayed- or missed diagnoses or just plain old inadequate care.

All of this combined can add up to an incredibly pervasive and ongoing source of stress.

This stress—in addition to being socially isolating and psychologically damaging—can further contribute to increased appetite and pleasure from high-calorie foods, decreased activity, and poorer sleep quality.³

Which is why…

Taking medication isn’t an “easy way out.”

In 2013, the American Medical Association categorized obesity as a disease.

And yet, many people still don’t treat it as such, and rather consider obesity as a willpower problem, and the consequence of simply eating too much and moving too little. (The remedy: “Just try harder.”)

In reality, people with obesity have as much willpower as anyone else.

However, for them, fat loss is harder—for all the reasons mentioned above, and more.

So, just like chemotherapy or insulin isn’t “the easy way out” of cancer or type 1 diabetes, medication isn’t “the easy way out” of obesity.

Rather, medication is a tool, ideally used alongside healthy lifestyle behaviors, that can help offset some of the genetic and physiological variances that people with obesity may have, and have little individual control over otherwise.

What you need to know about GLP-1 drugs

In 2017, semaglutide (a synthentic GLP-1 agonist) was approved in the US as an antidiabetic and anti-obesity medication.

With the emergence of this class of drugs, science offered people with obesity a relatively safe and accessible way to lose weight long-term, so long as they continued the medication.

How Ozempic and other obesity medicines work

Current weight loss medications work primarily by mimicking the function of glucagon-like peptide 1 (GLP-1), a hormone that performs several functions:

• In the pancreas, it triggers insulin secretion, which helps regulate blood sugar (and also helps you feel full).
• In the gut, it slows gastric emptying, affecting your sensation of fullness.
• In the brain, it reduces cravings (the desire for specific foods) and food noise (intrusive thoughts about food).

In people with obesity, the body quickly breaks down endogenous (natural) GLP-1, making it less effective. As a result, it takes longer to feel full, meals offer less staying power, and food noise becomes a near-constant companion, says Dr. Nadolsky.

Semaglutide and similar medicines flood the body with synthetically made GLP-1 that lasts much longer than the GLP-1 the body produces. This long-lasting effect helps increase feelings of fullness, reduce between-meal hunger, and muffle cravings and food noise.

Interestingly, by calming down the brain’s reward center (the part of the brain that drives cravings and even addictions), these medicines may also help people reduce addictive behaviors like compulsive drinking and gambling, says Dr. Nadolsky.

Note: Newer weight loss medicines, for example tirzepatide, mimic not only GLP-1, but also another hormone called gastric inhibitory polypeptide (GIP). Like GLP-1, GIP also stimulates post-meal insulin secretion and reduces appetite, partly by decreasing gastrointestinal activity. Other drugs soon to come on the market, like retatrutide, mimic a third hormone, glucagon.

How effective are GLP-1 drugs?

Researchers measure a weight loss medicine’s success based on the percentage of people who reach key weight loss milestones of 5, 10, 15, or 20 percent of their weight.

These medicines are still evolving, but so far, they have shown to be quite effective:

About 86 percent of people who take GLP-1 drugs like Ozempic, Rybelsus, and Wegovy lose at least five percent of their body weight, with about a third of them losing more than 20 percent of their body weight.^{4, 5}

And newer generation versions of these medications—such as tirzepatide, and the not-yet-FDA-approved retatrutide—are only getting better, with up to 57 percent of people losing more than 20 percent of their body weight.^{6, 7}

How do weight loss medications compare to lifestyle interventions?

In the past, weight loss interventions have focused on lifestyle modifications like calorie or macronutrient manipulation, exercise, and sometimes counseling.

Rather than pitting lifestyle changes against weight loss medicines or surgery, it’s more helpful to think of them all as compatible players.

With lifestyle modifications and coaching, the average person can expect to lose about five to 13 percent of their body weight.

When you add FDA-approved versions of GLP-1 and other weight-loss drugs to lifestyle and coaching, average weight loss jumps up another ten percent or more. ^{8, 9, 10, 11}

Fat loss often comes with powerful health benefits

For years, the medical community has told folks that losing 5 to 10 percent of their body weight was good enough.

Partly, this message was designed to right-set people’s expectations, as few lose much more than that (and keep it off) with lifestyle changes alone.

In addition, this modest weight loss also leads to measurable health improvements. Lose 5 to 10 percent of your total weight, and you’ll start to see blood sugar, cholesterol, and pressure drop.¹²

However, losing 15 to 20 percent of your weight, as people tend to do when they combine lifestyle changes with second-generation GLP-1s, and you do much more than improve your health. You can go into remission for several health problems, including:

• High blood pressure
• Diabetes
• Fatty liver disease
• Sleep apnea

That means, by taking a GLP-1 medicine, you might be able eventually to stop taking several other drugs, says Dr. Nadolsky.

Experts suspect GLP-1s may improve health even when no weight loss occurs.

“The medicines seem to offer additive benefits beyond just weight reduction,” says Dr. Nadolsky.

Research indicates that GLP-1s may reduce the risk of major cardiovascular events (heart attacks and strokes) in people with diabetes or heart disease.^{13, 14, 15} In people with diabetes, they seem to improve kidney function, too.¹⁶

The theory is that organs throughout the body have GLP-1 receptors on their cells. When the GLP-1s attach to these receptors in the kidneys and heart, they seem to protect these organs from damage.

For this reason, in 2023, the American Heart Association listed GLP-1 receptor agonists as one of the year’s top advances in cardiovascular disease.

7 strategies to make weight loss medicines more effective—and improve long-term health

Here’s what we believe:

Weight loss medicines don’t render lifestyle changes obsolete; they make them more critical.

When GLP-1 medicines muffle food noise and hunger, many find it easier to prioritize lean protein, fruits and veggies, whole grains, and other minimally processed foods. Similarly, as the scale goes down, people often feel better, so they’re more likely to embrace weight lifting and other forms of exercise.

Indeed, according to a 2024 consumer trends survey, 41 percent of GLP-1 medicine users reported that their exercise frequency increased since going on the medication. The majority of them also reported an improvement in diet quality, choosing to eat more protein, as well as fruits and vegetables.¹⁷

This is great news, because it further reinforces the idea that medication isn’t simply “the easy way out.”

(Of course, sometimes drugs are used as “the easy way out”; After going on medication, people can continue to eat poor quality food—just less of it. This increases the risk of losing critical muscle and bone, and losing less—or even no—body fat.)

When used correctly, weight loss medication is a tool that, as mentioned above, can make healthy lifestyle changes easier to accomplish, making both the drugs and the lifestyle changes more effective, and enhancing both short- and long-term success.

If you do decide to take weight loss drugs, use these strategies to get the most out of them—and preserve your long-term health.

Strategy #1: Find ways to eat nutritiously despite side effects.

The slowed stomach emptying caused by GLP-1 drugs can trigger nausea and constipation.

Fortunately, for most people, these GI woes tend to resolve within several weeks.

However, if you’re experiencing a lot of nausea, you’re not likely going to welcome salads into your life with open arms. (Think of how you feel when you have the stomach flu. A bowl of roughage doesn’t seem like it’ll “go down easy.”)

So, try to find more palatable ways to consume nutritious foods. (For example, fruits and vegetables in the form of a smoothie or pureed soup might be easier.)

Dr. Nadolsky also suggests people avoid the following common offenders:

• Big portions of any kind
• Greasy, fatty foods
• Highly processed foods
• Any strong food smells that trigger your gag reflex
• Sugar alcohols (like xylitol, erythritol, maltitol, and sorbitol, often found in diet sodas, chewing gum, and low-sugar protein bars), which can trigger diarrhea in some

Strategy #2: Prioritize strength training.

When people take GLP-1 weight loss medicines, about 30 to 40 percent of the weight they lose can come from lean mass.^{18, 19, 20}

Put another way: For every 10 pounds someone loses, about six to seven come from fat and three to four from muscle, bone, and other non-fat tissues.

However, there’s two important caveats to this statistic:

1. People with severe obesity generally have more muscle and bone mass than others. (Carrying around an extra 100+ pounds of body weight means muscles have to adapt by getting bigger and stronger.)

2. Muscle and bone loss aren’t inevitable. (As Dr. Nadolsky puts it, “Muscle loss isn’t a reason to avoid treating obesity [with medication]. It’s a reason to do more exercise.”)

To preserve muscle and bone mass, aim for at least two full-body resistance training sessions a week.

In addition, move around as much as you can. Walking and other forms of physical activity are vital for keeping metabolism healthy—and can help to move food through the gut to ease digestion.^{21, 22}

(Need inspiration for strength training? Check out our free exercise video library.)

Strategy #3: Lean into lean protein.

In addition to strength training, adequate protein consumption is vital for helping to protect muscle mass.

You can use our free macros calculator to determine the right amount of protein for you. (Spoiler: Most people will need 1 to 2 palm-sized protein portions per meal, or about 0.5 to 1 gram of protein per pound of body weight per day.)

Strategy #4: Fill your plate with fruit and veggies.

Besides being good for your overall health, whole, fresh, and frozen produce fuels you with critical nutrients that can help drive down levels of inflammation.

In addition to raising your risk for disease, chronic inflammation can block protein synthesis, making it harder to maintain muscle mass.

(Didn’t know managing inflammation matters when it comes to preserving muscle? Find out more muscle-supporting strategies here: How to build muscle strength, size, and power)

Strategy #5: Choose high-fiber carbs over low-fiber carbs.

Beans, lentils, whole grains, and starchy tubers like potatoes and sweet potatoes do a better job of helping you feel full and managing blood sugar than lower-fiber, more highly processed options.

(Read more about the drawbacks—and occasional benefits—of processed foods here: Minimally processed vs. highly processed foods)

Strategy #6: Choose healthy fats.

Healthy fats can help you feel full between meals and protect your overall health.

Gravitate toward fats from whole foods like avocado, seeds, nuts, and olive oil, as well as fatty fish (which is a protein too!)—using them to replace less healthy fats from highly-processed foods (like chips or donuts).

(Not sure which fats are healthy? Use our 3-step guide for choosing the best foods for your body)

Strategy #7: Consider coaching.

It may go without saying, but the above suggestions are just the start.

(There’s also: quality sleep, social support, stress management, and more.)

While many people choose to tackle these strategies on their own, many others find that the support, guidance, and creative problem-solving that a good coach can provide makes the whole process a lot easier—not to mention more enjoyable and more likely to stick.

And that’s the real gift of coaching: A coach doesn’t just help you figure out what to eat and how to move; They help you remove barriers, build skills, and create systems and routines so that habits become so natural and automatic that it’s hard to imagine not doing them.

Then, if you do want to stop taking medication, your ingrained lifestyle habits (that coaching reinforced, and medication perhaps made easier to adopt) will make it more likely that you maintain your results.

References

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