January 25, 2024

Obesity — unfortunately, a word as synonymous with America as New York City, baseball and McDonalds. With the rise in obesity and related diseases over the last 40 years came a corresponding surge of weight loss treatments. Everything from fad diets to surgery has had its time in the sun. Today, the topic on everyone’s mind and news feed is GLP-1s — a promising new treatment for weight loss with a staggering cost.

Obesity in America

Understanding expensive weight loss drugs starts with a look back at the rise of the obesity epidemic. Obesity, defined as anyone with a body-mass index (BMI) higher than 30%, has grown exponentially over the last four decades:

  • 1980: Obesity prevalence of 15%
  • 2000: Obesity prevalence of 31%
  • 2020: Obesity prevalence of 42%

Why? Well, that’s where things become a bit more complex. Many attempts have been made to identify the factors responsible, but no unified opinion has emerged. Leading theories include:

  • Reduction in physical activity
  • Increase in dietary fat
  • Increase in sugar and sugary beverages
  • Increase in ultra-processed foods
  • Higher cost of healthier diets

While the jury is still out on definitive root causes for the obesity epidemic, there has been a concerted effort to develop solutions and treatments.

Weight Loss Treatment Over the Years

Today’s cultural discussion on obesity treatment is dominated by GLP-1s, which follow a long line of medical weight loss treatments.

Early attempts to treat obesity came to the market as early as the 1930’s with dinitrophenol (DNP). While it increased metabolic rate, it was discontinued due to toxic effects.

In the 1940s and 1950s, amphetamines dominated as the obesity treatment drug of choice. The development and demand for these drugs increased steadily, reaching its heyday in the 1990s. However, prolonged use of many of these drugs revealed side effects which limited prospects as a long-term solution for obesity.

The late 1990s saw the return of weight loss medications with Xenical, first available as a prescription but now available over the counter as Alli. While effective, it came with undesirable side effects for patients. From 2012-2014, three more oral prescription drugs hit the market for obesity as Qsymia, Contrave, and Belviq. Belvig met a similar fate as earlier weight loss solutions — being pulled from the market in 2020 over concerns for increased occurrences of cancer.

The Rise of GLP-1s

Let’s begin with the basics: what is a GLP-1? The term GLP-1 is an abbreviation of Glucagon-like peptide-1. They are a type of peptide hormone that can stimulate the pancreas to produce more insulin after meals.

Additionally, they slow the movement of food from the stomach into the small intestine, which helps suppress appetite — meaning the patient feels full faster and longer. As a result, they eat less.

Discovery and Innovation

Researchers have been searching for insulin-stimulating factors for more than 100 years. 1902 saw the discovery of the first such hormones — secretin. The discovery of gastrin followed in 1905. It was not until 1984 that the first GLP-1 was discovered.

There was little initial excitement for the discovery, and further research and initial applications focused on diabetes treatment. By 2005, Byetta became the first GLP-1 approved by the FDA for the treatment of type 2 diabetes.

Since then, other GLP-1s agonists have come to market with FDA indications for diabetes treatment. Now you might be thinking, aren’t these drugs for weight loss? Not until recently.

GLP-1s and Weight Loss

During clinical trials, and in post-release surveillance, researchers observed that many patients taking GLP-1s experienced significant weight loss. As we discussed, pharmaceutical companies have been working on treatments for obesity for many years, and they were quick to investigate the use of GLP-1s for weight management purposes.

In 2014, the FDA approved Saxenda (liraglutide) as the first GLP-1 specifically for weight loss. Liraglutide was previously available for diabetes as Victoza. Later, in 2021 Wegovy (semaglutide) received the same indication. Semaglutide was previously available for diabetes as Ozempic and in an oral form for diabetes as Rybelsus. In a culture where obesity and weight management are a prominent discussion in society, these drugs have emerged as an important class of medications for managing weight.

Continued Innovation

2023 brought innovation to the GLP-1 weight loss conversation. On November 8, 2023, the FDA approved Zepbound (tirzepatide). Like the previous GLP-1s for weight loss, tirzepatide was previously available to treat diabetes under the brand name Mounjaro. Zepbound is the first GLP-1/GIP medications which is thought to be more potent than GLP-1 alone.

The term GIP stands for gastric inhibitory polypeptide. Like GLP-1 it is a peptide hormone that is responsible for insulin release after a meal with a variety of other impacts. While there are no head-to-head trials of GLP-1 medications to the GLP-1/GIP combination product, the combination product has resulted in a larger amount of weight loss in clinical trials than the previous GLP-1 products.

Looking Ahead

The rise of GLP-1s has been meteoric. Between 2018 and 2023, prescriptions for these drugs increased by a staggering 300%. Their effectiveness, relative safety compared to previous medications and convenience have propelled them to the forefront of the weight loss treatment landscape.

However, the GLP-1 story is not without its complexities. The prohibitive cost of these medications raises concerns about accessibility and exacerbating healthcare disparities. Questions also linger for those responsible for pharmacy benefits — how can they manage the long-term impact of these medications on their plan and its members?

As the pipeline continues to grow, and demand for medication therapy for weight loss continues, it is vital to understand what strategies your PBM can deploy to ensure appropriate utilization. Finding the right pharmacy benefit consultant that understands the complete clinical landscape of this emerging area will be paramount.

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