GLP-1 agonists: A new class of weight loss medications

The implications of new obesity drugs

One of the most pronounced changes in the pharmacy landscape over the past year has been the rapid emergence of a new class of medications for weight loss known as GLP-1 agonists.

In a recent episode of the Pharmacy Insights Podcast, Optum Rx convened a trio of thought leaders to discuss the emergence of the GLP-1 class. Optum Rx senior vice president of clinical consulting, Scott Draeger, welcomed:

• Dr. Ana Bhatnagar, Optum Rx associate chief medical officer 
• Dr. Travis Baughn, Optum Rx vice president of Clinical Solutions

They unpack the interesting backstory of GLP-1s as a treatment for Type 2 diabetes and discuss what broader use of these promising but expensive medications for weight loss means for both patients and plan sponsors.

Listen to the full "The Seismic Shift in Weight Loss Medicines" podcast episode or read the lightly edited excerpts of this timely conversation:

The diabetes and obesity connection

Scott Draeger: I've noticed that in much of the pharmaceutical direct-to-consumer advertising, the line between diabetes and obesity treatments really seems to blur. Ana, how are these two conditions related, and why does it seem that we hear so much more about both conditions lately?

Dr. Ana Bhatnagar: That's a great question, Scott. Both diabetes and obesity are metabolic conditions, and one reason we are hearing more about them is because there are some new therapies that were originally used for diabetes that are now being studied and approved for use in weight loss.

Type 2 diabetes is the most common form of diabetes in adults. It's a chronic disease, and high blood sugar levels are the hallmark. More than 80% of cases of Type 2 diabetes can be attributed to obesity. Obesity is also chronic condition in which individuals have a weight that is higher than what is considered healthy for their height. There's evidence that certain individuals have a predisposition to obesity, and the underlying mechanisms within the body, their genetic makeup and environmental factors, all contribute to a tendency to gain weight. Also, certain medications or medical conditions can also lead to obesity. What's interesting is that 30% of overweight individuals have diabetes. So not everyone who's obese has diabetes, but they do have a higher risk.

Scott: Ana, you mentioned that diabetes is a chronic condition. I think most people understand that. Should we think of obesity in the same way?

Ana: We can consider chronicity of both conditions because there are demonstrated worse health outcomes if they are left untreated. For diabetics that are overweight or obese, weight loss can improve their control and their outcomes overall as far as heart disease and other adverse outcomes. And for those with obesity, we know they have a higher risk for diabetes, heart disease and sleep apnea related to having a higher BMI.

Scott: So, Ana, in your opinion, why has obesity been so difficult to treat traditionally?

Ana: Like any chronic condition, Scott, the approach to treatment must be multi-pronged and have a focus on improved health overall.

The processes within the body that lead to obesity are still being researched, but the human body is designed to store energy and have a positive energy balance. For that reason, it’s difficult to sustain a highly calorie-restricted diet for a long time and achieve weight loss.

The most successful interventions for weight loss have a goal both to maintain the decrease in weight and an adherence to change in lifestyle as well. There've been many weight loss treatments available in the past, with some have up to 11% weight loss benefit, but these newer agents that we've alluded to have a greater efficacy because they have a greater response rate than the previous agents. That means more individuals taking them are likely to lose weight.

Scott: Travis, let's switch gears here a little bit and talk a little bit more about your area of specialty, medications. There's been much talk in the lay press about new “wonder drugs” for the treatment of obesity. What has specifically changed in how we treat this condition with pharmaceuticals? And in your opinion, are these new medications actually better?

Dr. Travis Baughn: Thanks, Scott. That's a great question. The drug landscape has really evolved quickly as of late.

Before these GLP-1 medications were approved for weight loss, we had a variety of marginally effective medications that were primarily only used short term. These medications, such as phentermine and diethylpropion, are appetite suppressants and come with concerning adverse effects and incredibly variable outcomes.

Over time, we had continued innovation in the obesity medication space. We had a couple of combination drugs approved such as Contrave® and Qsymia® that combined existing FDA-approved molecules together. These medications were impressive and showed weight loss benefit. So, there was excitement around our ability to treat obesity effectively. It was these agents that really paved the way for continued pharmacologic innovation.

Now, enter the GLP-1s. Over the past decade, they came aboard as an innovation in treating diabetes. The profound impact seen on creating weight loss was in some ways unexpected. In essence, it was through the clinical trials for these drugs to treat diabetes that the large effect of creating weight loss was first realized. In the trials, GLP-1 drugs produced double-digit percentage weight loss without dramatic adverse effects.

Moreover, later this year, we are likely to see results from a monumental clinical study, the Phase 3 Select Trial. When completed, that will answer the key question of whether there is a meaningful positive cardiovascular outcome effect for obese individuals taking a GLP-1 for weight loss. We’ll have to wait until we get the results of that trial, but there's an expectation in the industry that this connection between GLP-1s and cardiovascular health protection will be confirmed.

To me, this is the “wonder drug” mentality. You would have one drug effectively creating weight loss but also being statistically proven to improve cardiovascular health. So, yes, these drugs are in some ways better, but they come with a hefty price tag and a ton of hype as well.

The question we need to evaluate deeper is do these drugs produce a sustainable weight loss outcome and how does that cardiovascular protection improve patient health in the long term? And at the root of it all is how can we manage the cost and get the price lower so the health care ecosystem can treat all patients who could benefit from these medications?

How GLP-1 medications work

Scott: Given this intersection between obesity and diabetes, it makes sense, at least on the surface, why there would be an intersection in terms of the medications used to treat both conditions. Can you give some specifics on how these GLP-1s work in the body and how we think it's leading to the weight loss?

Travis: Absolutely. The mechanism of action of GLP-1s is really unique. The “GLP” in GLP-1 stands for glucagon-like peptide. It's a hormone in the body that's critical in managing appetite and managing your insulin and glucagon levels. It also plays a huge role in stomach emptying or the feeling of being full of food in your stomach.

So, these GLP-1 agonists in essence mimic these hormones in the body. When you take the medication, it creates an effect of the patient being able to better regulate their food intake and also better manage insulin and glucagon levels after meals.

The current obesity-approved GLP-1s are all injectable, with the newer agents being once-weekly injections. Thus, one injection a week creates a meaningful impact on reducing food intake. Just to note, there is one oral diabetes GLP-1. It’s likely to also eventually be available with a weight loss indication. I fully anticipate we will start to see other oral GLP-1s for weight management in the pipeline over time.

Scott: Travis, how much weight loss do these new GLP-1s medications typically achieve in patients? And, and how does that compare to some of the older pharmaceuticals you referenced a little bit earlier on in terms of their treatment of weight loss?

Travis: As you’d expect when looking across multiple drugs, the results vary a bit, but with every new approval of a GLP-1 for weight loss, the results get better and better.

For the original obesity-approved GLP-1, Saxenda®, weight loss is around 5% to 6% on average. For Wegovy®, we see about 14% to 15%. Tirzepatide, currently approved for treatment of diabetes under the brand name Mounjaro™, may be approved with outcomes exceeding 20% weight loss.

I think one thing that sometimes gets glossed over, though, is how fast this can happen. Current studies vary product by product, but with tirzepatide, for example, patients can exceed 10% weight loss in as quickly as 20 weeks. It takes another year or so for the weight loss to fully plateau, but 10% in 5 months is impressive.

The older treatments I mentioned earlier were squarely in the mid to maybe upper single digit effectiveness. Discontinuation rates were very high, and motivation was low due to adverse effects, and the ability to sustain the weight loss was questionable at best. These agents are far superior to the old treatments in nearly every way, but again — expensive.

Scott: I mentioned earlier that this line between diabetes and weight loss has really blurred. For example, you have a medication like Ozempic, which is a heavily advertised GLP-1 medication used in the treatment of diabetes. There have been reports in the lay press that physicians have been using this treatment to aid in weight loss as well. You mentioned the weight loss-specific medication that came to the market in the past year called Wegovy. My understanding is that both Ozempic and Wegovy are the same drug chemically. Can these two medications be used interchangeably for weight loss?

Travis: Ozempic and Wegovy are both branded semaglutide products. However, they are different strengths — studied and tailored to their respective indications. So, despite being nearly identical pharmacologically, they are not able to simply be interchanged.

I think that some of the press coverage and general conversation that blurs the line between the two is just a reflection of the fact that Ozempic was first to market. The bottom line is that prescribers should be prescribing Ozempic for diabetic patients for treatment of diabetes and Wegovy for non-diabetic patients for treatment of obesity. Obviously, you shouldn’t be on both at the same time.

Cost, durability and safety

Scott: So, I think the question that consumers especially want to know is how much do these new GLP-1s medications for weight loss typically cost?

Travis: They're not cheap. The net price of these medications on average hover between $800 to 900 per month. That puts the total cost around $10,000 annually. Keep in mind, the older weight loss drugs I referenced earlier were less than 10% of that cost.

Given this dramatic difference in cost, it really underpins the need to think creatively about management here. We need to get the cost down.

Scott: Ana, from your perspective, do you believe that these new drugs are safe? What type of side effects do patients typically see when using these types of medications?

Ana: As Travis noted, we've been using GLP-1s for many years in the diabetes space. So, we have some years under our belt with these chemical entities being used, and they have a pretty good safety profile.

However, since the drugs work by slowing down stomach emptying as mechanism of action, some of the common side effects we see are nausea, constipation and abdominal discomfort. Also, there is a risk for certain individuals with a predisposition for hereditary cancers.

Scott: Ana, with some of the older weight loss medications, the rate of recidivism, that is the tendency to gain the weight back, is rather high. How sustainable is the weight loss with these GLP-1 medications?

Ana: So that’s a question that remains to be answered. The evidence behind the GLP-1 medications is exciting, but there’s an absence of long-term studies.

We need more research on the long-term outcomes like sustainable weight loss. That said, some individuals may benefit from short-term use to lose enough weight to derive a clinically meaningful benefit. We’ve seen that even a 5% weight loss can improve diabetes control and other health outcomes.

Scott: Travis, you oversee clinical solution development at Optum Rx. As you look at how to address obesity across the populations that you serve, what are the critical elements and how do you plan to incorporate them into a solution?

Travis: I really think of this from two lenses: the patient and payer.

For the patient, we’ve got to absolutely respect the fact that all patients are unique with obesity. An obesity journey can be very different patient by patient, and response to therapy can vary drastically as well. This need to personalize both the potential qualification for treatment, as well as personalize the support delivered to the patient to achieve behavioral change that drives that weight loss is at the foundation of the solution we are developing.

One huge concern that many have with these medications is duration of therapy and durability of the achieved weight loss. Patients will lose weight. Will they keep the weight off? Only if they adopt the healthy behaviors that allow them to sustain the weight loss. There of course may be patients who stay on the medication long term, but not everyone will. How can we support members transitioning off the medication?

From the payer lens, the fact is these drugs are expensive. These drugs are expensive, and everyone wants them — regardless of if they are even clinically overweight or obese. Also, not all patients have the same motivation, and motivation is key for success. Our solution needs to solve for these areas: managing access, managing cost and ensuring motivation and behavioral change through enforcing required program participation.

This will be a solution that pulls together several components to help plans manage their weight loss drug costs, help members achieve their weight loss, and ensure sustained weight loss long term to improve their overall health.

Scott: Ana, I want to conclude with this. What type of things would you recommend patients consider before asking their physician about treatments for obesity, and how will they know it's the right time to see their physician?

Ana: Scott, I think we've pulled this thread through our entire conversation here, is that the goal of treatment of any chronic condition, even obesity, is really to support overall health outcomes and quality of life. So, that decision will be individual to each patient.

While these newer medications have brought this conversation to the forefront, there are multiple options that can lead to weight loss and ultimately support improved overall health and quality of life. Health benefits are seen with the weight loss as little as 5% of body weight. Patients should discuss weight loss and the options available to them based on their weight loss goals and need to manage other conditions.