If you’re unfamiliar with the term “GLP-1”, chances are you’re familiar with the products in this drug class and their brands. Oh-Oh-Oh-Ozempic! might be one of the most recognizable marketing campaigns in recent memory, healthcare or otherwise.

The launch of GLP-1s and similar drugs for weight management has sparked an understandable fervor in the healthcare industry and in the minds of consumers. In the United States, nearly three-quarters of the population is either overweight or obese.¹

As evidenced by the unprecedented publicity and patient demand for these medications, GLP-1s have cemented their place in the conversation around how to address overweight, obesity, and the numerous conditions that coexist (e.g., diabetes, cardiovascular disease, etc.). At the same time, GLP-1s are arguably not designed to be the miracle drugs they are often characterized to be.

GLP-1(01) – What is GLP-1?

Before we get into GLP-1 drugs like Ozempic, we should understand the underlying science behind them. GLP-1 stands for Glucagon-Like Peptide-1. GLP-1 is a hormone naturally produced by the body, which induces several effects (in no particular order):

GLP-1’s Metabolic Effects²

Cause	Effect
Slows gastric emptying (digestion)	Appetite decreases
Increases satiety (the feeling of being “full”)	Appetite decreases
Stimulates (increases) the secretion of the hormone insulin	Blood glucose decreases
Suppresses (decreases) the secretion of the hormone glucagon	Blood glucose decreases

Uniquely, the GLP-1 hormone causes both physical and neurological effects on appetite. First, the physical act of slowing gastric emptying means food is not making its way through our digestive tract at the normal rate. Hence, if we physically have not processed the food we ate, we don’t feel the need to eat more.

Second, the neurological feeling of “being full” is when the brain receives signals and hormones indicating that food has been eaten. The GLP-1 hormone acts in such a way that the brain receives these signals to stop eating. Hence, our appetite, or desire to eat, decreases.

GLP-1 has additional metabolic effects, most notably on blood glucose (aka blood sugar), which may be better understood in the context of their early development as pharmaceuticals.

GLP-1(02) – What are “GLP-1s”?

GLP-1s is the colloquial acronym for a specific type of drug more formally known as GLP-1 Receptor Agonists (or GLP-1 RAs). These drugs are formulated to mimic the naturally occurring GLP-1 hormone and induce the same effects outlined above.

Given their recent publicity and media coverage, what may come as a surprise is that GLP-1s have been FDA approved for nearly 20 years. As referenced above, GLP-1 regulates other hormones, insulin and glucagon, that results in a lowering of blood glucose. Thus, GLP-1s have historically been prescribed primarily to treat conditions where blood sugar is elevated, namely Type 2 diabetes (T2D).

Hormone	Change	Effect on Blood Glucose (Blood Sugar)
Insulin	Increase	Decrease
Glucagon	Decrease	Decrease

In developing GLP-1s for T2D, researchers noticed secondary benefits, most notably appetite suppression and corresponding weight loss. However, without an FDA approval for weight management, GLP-1s could not be promoted for this use. As such, companies initiated clinical trials studying GLP-1s specifically for weight management, with several having since received FDA approval.

FDA Approved GLP-1 Receptor Agonists

Brand	Generic Name	Manufacturer	Mechanism	Approved For
Ozempic	semaglutide	Novo Nordisk	GLP-1 Receptor Agonist	Type 2 Diabetes
Wegovy	semaglutide	Novo Nordisk	GLP-1 Receptor Agonist	Weight Management
Rybelsus	semaglutide	Novo Nordisk	GLP-1 Receptor Agonist	Type 2 Diabetes
Mounjaro	tirzepatide	Eli Lilly	GIP and GLP-1 Receptor Agonist	Type 2 Diabetes
Zepbound	tirzepatide	Eli Lilly	GIP and GLP-1 Receptor Agonist	Weight Management
Trulicity	dulaglutide	Eli Lilly	GLP-1 Receptor Agonist	Type 2 Diabetes
Saxenda	liraglutide	Novo Nordisk	GLP-1 Receptor Agonist	Weight Management
Victoza	liraglutide	Novo Nordisk	GLP-1 Receptor Agonist	Type 2 Diabetes
Byetta	exenatide	AstraZeneca	GLP-1 Receptor Agonist	Type 2 Diabetes
Bydureon BCise	exenatide	AstraZeneca	GLP-1 Receptor Agonist	Type 2 Diabetes

This dynamic explains how the same molecule (e.g., semaglutide) can have multiple brands (e.g., Ozempic and Wegovy), which are only differentiated by the indication (i.e., use) they are approved for (Type 2 diabetes and weight management, respectively).

What does the science behind GLP-1’s suggest about weight loss and weight management?

The science behind GLP-1s in the context of weight loss is fairly straightforward:

1. Slow gastric emptying and increase satiety = decreased appetite
2. Decreased appetite = less desire to eat
3. Less desire to eat = less food eaten
4. Less food eaten = fewer calories consumed
5. Fewer calories consumed = weight loss (all else being equal)

Therefore, it is somewhat unsurprising how effective these drugs have been in helping individuals lose weight. However, arguably the biggest challenge for anyone taking GLP-1s is when weight loss (defined as a one-time change) becomes weight management (defined as the long-term maintenance and lifestyle changes needed to sustain that change).

Let’s consider the exact language used in the Food and Drug Administration (FDA) label for Wegovy, which is the document that describes how and for whom this drug can be prescribed:

Excerpt from Wegovy’s FDA label³

GLP-1s like Wegovy for weight management are intended to be used “as an adjunct to” (in other words, as a non-essential addition to) lifestyle changes such as a lower calorie diet and increased exercise. Specifically, participants involved in the clinical trials were counseled to eat at least 500 fewer calories per day AND achieve a minimum of 100-150 minutes/week of physical activity. In some parts of these clinical studies, participants were eating a few as 1,000-1,200 calories per day, while also increasing their physical activity.^3,4,5

Separately, the BMI criteria for eligibility can be a source of confusion as to if and/or how these drugs work, but the explanation is likely quite simple.

Currently, GLP-1s approved for weight management (Wegovy, Zepbound, and Saxenda) are only approved for individuals with obesity (BMI of 30 kg/m² or higher) OR overweight (BMI of 27 kg/m² or higher) and a comorbidity (e.g., high blood pressure, Type 2 diabetes, cardiovascular disease, etc.). As an aside, this does not prohibit physicians from prescribing GLP-1s “off-label” for individuals that do not meet these criteria, but we will stick to the approved label for the sake of this article.

Source: Wegovy FDA label³

These criteria should not be interpreted to suggest that GLP-1s don’t work or stop working if an individual has a BMI below 27 kg/m² (i.e., not overweight or obese). Instead, I suspect these medications were studied in overweight and obese populations because it would demonstrate the largest positive effect on weight loss and related conditions relative to non-overweight populations.

The Role of GLP-1s for Long-Term Weight Management

Given the relatively short period of time people have been taking GLP-1s for weight management, what remains to be seen is what happens when individuals stop taking these medications. Presumably, just like most other drugs, the effects of taking GLP-1s are only realized to the extent and duration they are taken. Said differently, the effects are likely to be lost as soon as someone stops taking them.

As such, when it comes to long-term weight management, lifestyle changes, such as those outlined in the clinical trials, are essential. Such is not to say GLP-1s play no role. Rather, I would argue GLP-1s should be viewed as highly effective, but only temporary supplements that accelerate the results achieved through diet and exercise.

Putting It All Together

Despite all the fanfare, the science behind GLP-1s demonstrates that there remains no substitute for lifestyle practices such as caloric restriction and exercise when it comes to weight loss and long-term weight management. There may very well be a lot of good that comes from GLP-1s in affecting accelerated results in individuals with overweight and obesity; however, without conscious lifestyle change, individuals are unlikely to sustain the stellar results achieved on these medications.

Sources:

1. https://www.niddk.nih.gov/health-information/health-statistics/overweight-obesity
2. Müller, T., Finan, B., Bloom, S., D’Alessio, D., Drucker, D., Flatt, P., Fritsche, A., Gribble, F., Grill, H., Habener, J., Holst, J., Langhans, W., Meier, J., Nauck, M., Perez-Tilve, D., Pocai, A., Reimann, F., Sandoval, D., Schwartz, T., . . . Tschöp, M. (2019). Glucagon-like peptide 1 (GLP-1). Molecular Metabolism, 30, 72–130. https://doi.org/10.1016/j.molmet.2019.09.010
3. Wegovy FDA label: https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/215256s000lbl.pdf
4. Saxenda FDA label: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/206321s007lbl.pdf
5. Zepbound FDA label: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/217806s000lbl.pdf