GLP-1s and Weight-Loss Medications vs. Lifestyle Interventions: What’s Right for You

Written and medically reviewed by Rich LaFountain, PhD

Injectable GLP-1 receptor agonists, often known by brand names such as Ozempic, Wegovy, Mounjaro, and Zepbound, are a hot topic in the world of weight loss. In less than a decade, they have skyrocketed in popularity as an effective weight-loss tool. However, they are not the only effective weight-loss tool. Let’s take a closer look so you can make an informed decision about the best weight-loss intervention for you. Plus, we’ll share insights from our Chief Medical Officer, Naomi Parrella, along the way.

Weight Loss and How It’s Evolved in the Last 50 Years

Over the past half-century, clinical and research focus on weight management has transformed popular approaches to weight loss. In the 1970s and 1980s, weight loss was predominantly associated with calorie restriction and increased physical activity. “Eat less, move more” was the mantra that summarized the vast majority of weight-loss interventions. As part of this philosophy, low-fat diets gained popularity, and the burgeoning field of exercise science contributed an array of diverse exercise programs. Yet despite the numerous articles, books, and products dedicated to the subject, sustainable weight loss remains a challenge. Of those who successfully manage to lose weight, the majority end up gaining it back.

In the twentieth century, pharmaceutical interventions aimed at addressing overweight and obesity emerged, but these often came with significant side effects and limited efficacy. Then, GLP-1 receptor agonists were discovered as a promising weight-loss tool. These medications were initially approved about 20 years ago for managing diabetes, but they also turned out to produce significant weight loss. Clinicians have found that pharmaceutical interventions like GLP-1 receptor agonists can play a pivotal role in helping people experience weight-loss success, especially when they are paired with healthy lifestyle habits.

What Are Lifestyle Interventions? Are They Enough?

Lifestyle interventions (a.k.a. “healthy habits”), particularly nutrition and exercise, remain at the forefront of healthy weight-loss strategies. The benefits associated with healthy nutrition, movement, sleep, and stress management habits go beyond just weight loss. For example, research demonstrates that combining dietary modifications with increased physical activity can lead to significant reductions in body weight, improvements in metabolic health, a reduced risk of obesity-related comorbidities, and lifespan extension of 12–14 years.

“Because a number of weight-related conditions, like diabetes and high blood pressure, as well as pain, sleep, and even mood can also be improved or resolved with simple, targeted lifestyle adjustments, many people choose to hold off on committing to lifelong medications until they discover what’s possible without those medications.”

  • Dr. Naomi Parrella, MD

Habits make up a large percentage of your waking behavior; therefore, investing in healthy habits may be equated to administering “natural medicine” at various points throughout your day. Certain science-backed habits, like intermittent fasting, can give you the most bang for your buck — and you don’t have to try to adopt these habits alone. Zero, for instance, uses a unique blend of education, motivation, and accountability to help you to form the right habits to improve your metabolic health by unlocking fat burning. That way, you can achieve healthy weight loss without the risks or side effects associated with medical interventions, including GLP-1 injections. Notably, the holistic nature of lifestyle habits like intermittent fasting, regular exercise, quality sleep, and stress reduction facilitates sustainable weight loss along with myriad benefits to quality of life

Of course, despite the overwhelming positive effects of a healthy lifestyle, challenges associated with food environment, sedentarism, poor sleep, and chronic stress present a significant headwind. In some cases, it’s appropriate to bolster a healthy lifestyle with medicines like GLP-1 receptor agonists to reach a healthy weight. Combining the two interventions can produce positive results and has the added benefit of minimizing certain known side effects of GLP-1 receptor agonists.

What Are GLP-1s? How Do They Work?

GLP-1 receptor agonists are positioned as a valuable addition to the toolkit available for fighting obesity. By providing an intervention that is a quick (albeit often expensive and recurring) injection, they offer a possible solution for individuals struggling with weight-related health issues who are unwilling or unable to achieve their desired or medically necessary weight loss solely through healthy lifestyle habits.

GLP-1 receptor agonists are a class of pharmaceutical compounds that mimic the function of the metabolic hormone glucagon-like peptide-1 (GLP-1). When you eat, your body naturally produces and releases GLP-1 in order to prime your system to manage the glucose you consume in your meals — namely by promoting the release of insulin. (Research shows that 70% percent of your insulin secretion after a meal is a result of hormones like GLP-1.) GLP-1 receptor agonists work by binding to and activating the GLP-1 receptors in the pancreas.

In doing so, they cause the same reactions as the natural hormone: enhancing insulin secretion, reducing glucose levels, and promoting a feeling of fullness. Therefore, these medications ultimately produce weight loss by causing you to feel fuller and consequently eat less food than you otherwise would. Clinical trial data following patients for over 18 months suggest roughly 86–89% of participants lose and maintain ≥5% of their body weight with the help of GLP-1 receptor agonists. 

“To date, weight regain occurs after discontinuing weight-loss medication, so think of it as a lifelong commitment.”

  • Dr. Naomi Parrella, MD

What Other Weight-Loss Medications Are Out There?

Not everyone can tolerate the side effects of GLP-1 receptor agonists, and for some people, the injection requirement is a nonstarter. For these individuals, alternative oral medications that have demonstrated efficacy in promoting weight loss include: 

“Compounded formulations of the medications are not the same as the brand name medications from Novo Nordisk or Lily, and they may not be safe to use.”

  • Dr. Naomi Parrella, MD

As this brief list demonstrates, different weight-loss medications vary in their mechanism of action, or how they work. This means that some work better for certain people than others and, in cooperation with your doctor and healthcare team, you can find an option that best suits your individual needs and preferences. It’s worth noting that according to research, weight-loss medications are often best tolerated and more effective when paired with healthy lifestyle choices. In fact, clinical guidelines suggest that GLP-1 receptor agonists and other pharmacological approaches to weight loss should be considered in conjunction with lifestyle intervention — so choosing a lifestyle or medication intervention for weight loss isn’t necessarily “either/or.”

How Do I Make the Right Choice for Me?

If you are contemplating a weight-loss intervention, you’ll want to take several factors into account. Lifestyle intervention remains the first, best option to avoid side effects and medical costs as well as create lasting change so you can maintain your healthy body weight in the long term. Deciding to pursue GLP-1 receptor agonists for weight loss requires careful consideration of individual health factors and consultation with your physician. Here are a few factors to consider:

  • Individuals with type-2 diabetes or obesity, particularly those struggling to achieve adequate glycemic control or experiencing significant challenges with body-weight management, are most often considered candidates for GLP-1 receptor agonists.
  • GLP-1 receptor agonists are costly, so you may want to determine whether you qualify for insurance coverage before you pursue this treatment option.
  • Factors such as lifestyle and the commitment to adhere to the prescribed regimen will influence your candidacy for (and desire to take) this medication. Discuss these factors, as well as any existing health conditions, medications, and allergies, with your healthcare team as you evaluate your options.
  • Regular, honest, open communication with your doctor will be important to monitor the medication’s effectiveness, manage potential side effects, and make necessary adjustments. Ensure you have a strong relationship with your doctor so you are comfortable sharing openly and communicating often if you choose to pursue GLP-1 receptor agonists for weight loss.

“While weight-loss medications such as GLP-1s, can be part of a successful weight-management strategy, it is important to understand how to think about and use them appropriately. When patients visit my clinic to start weight-loss medications like GLP1s, they are often surprised to learn that these medications are intended to be continued long term. Weight regain is normal and expected if these medications are stopped. There are also substantial risks, and common side effects that often persist include nausea and upset stomach. When people hear about the risks and side effects and learn that they will need to take the medications for a long time, even after they achieve their weight-loss goal, they often want to try something else first.”

  • Dr. Naomi Parrella, MD

Ultimately, the decision to use GLP-1 receptor agonists should be a collaborative and fluid decision-making process so the most suitable and effective treatment approach can be tailored to your needs. Remember: You can always start with a lifestyle intervention like Zero and consider medical intervention later down the line.

Conclusion: Making the Right Decision Around Weight-Loss Interventions Requires Being Fully Informed

Weight loss is rarely easy, and it’s almost always a long-term commitment. Therefore, it’s important to understand your options so that you can find tools and solutions that work best for you. GLP-1 receptor agonists and related therapies have gained popularity for their effectiveness, but the risks and benefits should be factored into your decision to take this medication or any other intervention for weight loss.

In addition, remember that these medications lead to weight regain if they are not continued, and side effects and cost are important to consider, as well. If you have yet to try a lifestyle intervention, there’s no harm in starting there before looking into medication for weight loss. After all, these treatments work best when combined with healthy lifestyle habits!

Rich LaFountain, PhD
Posted in Health & Science

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