GLP-1s: Real-life wonder drugs?

But the real GLP-1 story appears to be just getting started. One sign of this is that research into using GLP-1s to treat still more conditions has exploded. 

In January of this year we published an article describing some of the potential new uses being investigated for GLP-1 drugs. As our earlier article showed, the possibilities range across any number of body systems, touching Alzheimer’s disease, fatty liver disease, arthritis, pain relief and even certain types of cancer.

This graph shows that the number of journal articles on this topic has surged by more than 2000% since 2000. These include reports on both lab work and clinical trials: 

In some cases, the problems GLP-1s can solve stem directly from their weight reduction effect. For example, we mentioned the new indication to treat sleep apnea. The supporting studies clearly show that apnea symptoms are reduced because of lower body weight.⁷ 

But other cases are more complex, like osteoarthritis. GLP-1 receptor agonists are being used now off-label to treat osteoarthritis in clinical practice with promising results.⁸ 

In part, its benefit is also derived from lower body weight – allowing less stress on the joints. But GLP-1 drugs may also counteract osteoarthritis metabolically, by working in the cartilage and other bone tissue found inside the joint.⁹ 

This speaks to the extremely fundamental processes affected by GLP-1 drugs. The more widespread and useful a process is, the more body parts are affected by it. And any drug that influences a foundational process is going to have very widespread effects.¹⁰

This illustration summarizes some of the ways GLP-1 drugs work across different body systems. Some of their effects are direct, but others occur indirectly as the result of complex interactions, many times mediated by the brain: 

If we want to talk about a fundamental process that is widespread throughout the body, inflammation definitely fills the bill.

Inflammation is an important part of our body’s natural defense system, and is crucial for healing and recovery. However, unchecked chronic inflammation can lead to many different diseases. In fact a recent group article written by several prestigious journals was titled, “Inflammation: The cause of all diseases.”¹¹ 

One of the most important effects of GLP-1 drugs is their ability to reduce oxidative stress and inflammation.¹² In turn, chronic inflammation reveals an indirect link between GLP-1s and the brain. 

Recent work shows that there is a GLP-1-brain-immune pathway that controls inflammation across the body.¹³ In other words, GLP-1 medicines reduce disease complications directly and indirectly in overlapping ways, perhaps most importantly by reducing chronic inflammation.¹⁴ 

The reason GLP-1 drugs are so effective at leveraging the brain to fight inflammation is that, while they mimic the effects of the natural GLP-1 hormone, they are synthetic drugs. So their effects last far longer – up to a week – than the natural hormone, which is typically degraded within a few minutes.¹⁵   

The extra durability from being synthetic allows the drugs a better chance to enter the brain. This is very different from how our body usually works.¹⁶

Inflammation is tightly tied to conditions such as Alzheimer’s disease, Parkinson’s disease, and other dementias. For example, insulin resistance is emerging as a key indicator of Alzheimer’s disease and Parkinson’s disease. GLP-1 drugs work to counteract insulin resistance by increasing insulin sensitivity in neurons.¹⁷ 

These effects are so strong that the title of one recent paper rather provocatively announced that, “All GLP-1 Agonists Should, Theoretically, Cure Alzheimer’s Dementia…”.¹⁸

The author’s logic is simple: Since the underlying cause of dementia is dysfunction in some specific brain cells, we need to fix or prevent those dysfunctions. In turn, GLP-1 agonists affect all of the major dysfunctional brain cell types related to Alzheimer’s, and so may potentially cure dementia. This researcher believes that the reason this hasn’t already been shown is because the available GLP-1 drugs differ in their ability to enter the brain, and in their beneficial effects.¹⁹  

Given the possibility that existing GLP-1 drugs are insufficient for treating Alzheimer’s and Parkinson’s disease, some researchers are studying new versions of GLP-1s designed to solve that exact problem.²⁰  

These are just a few of the many possibilities being explored as we speak.

Depending on how the new research turns out, adding some of the indications discussed here could add many millions of potential patients who might benefit from GLP-1 medicines. For example, as this was written, we received news that the FDA had approved the GLP-1 Wegovy® to treat the common liver condition called MASH (or, metabolic dysfunction-associated steatohepatitis). This indication affects about 22 million people in the U.S.

If plan sponsors thought it was expensive to treat obesity with GLP-1s, how will they react to these additional new costs?

Of course there’s always been a theoretical argument that, by managing long term conditions like obesity, plan sponsors would eventually see reduced health care costs overall. But it’s hard to make coverage decisions based on theories.²¹ 

But now we are seeing hard evidence that may make covering GLP-1s a more palatable call. A study published in April of this year compared health outcomes over two years for people who took GLP-1s versus those who did not. The results were striking. GLP-1 users saw a 44% reduction in hospitalizations due to stroke, heart attack and heart failure compared to the control group.²² 

Looking down the road at possible costs, there are grounds for optimism. Early news stories about GLP-1s, particularly as they are used for weight loss, forecast sky high sales within just a few years. For example, Goldman Sachs had been projecting sales of $130 billion by 2030. But more recently they have revised their numbers; they now see a much smaller growth – nearly one third less (27%) – to $95 billion.²⁶   

The main reason for the shift is that Goldman Sachs now expects GLP-1 prices to decline much faster than originally. They now believe that prices will fall by 7% per year, versus only 2% in their original forecast.²⁷  

Similarly, a different group (Morningstar Equities) predicts that GLP-1 prices could begin to fall 10%-15% per year beginning in 2027. This is based on trends observed in other drugs, including increased competition and regulatory pressures.²⁸

Plan sponsors need an expert partner with the capabilities to provide effective management strategies. Optum Rx has introduced a host of tools at the formulary and benefit design levels, to ensure GLP-1 drugs are used responsibly.

For example, our pipeline and drug surveillance teams continuously monitor new drug launches, formulations and indications of GLP-1s. Then, our independent Pharmacy & Therapeutics (P&T) Committee reviews clinical and safety information, and provides recommendations for formulary inclusion.

For clients considering GLP-1s for obesity, Optum Rx has created clinical programs designed to provide ongoing monitoring and motivation for members taking these drugs. Optum Rx Weight Engage helps members achieve and sustain their weight loss goals through behavior modification support, such as diet and exercise planning.

As new uses for GLP-1 medications arise, we believe plan sponsors should start preparing now for increased demand and develop a program approach that balances appropriate access with maintaining benefit affordability.

Optum Rx can provide precision analytics to demonstrate cost impacts spanning multiple scenarios, as well as expert clinical consultation and insights to help you make timely decisions.