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As GLP-1 drugs continue to surge in popularity, pharmaceutical companies are racing to bring new, more effective versions to the market. Writing for the Washington Post, Christopher Rowland outlines three ways companies are working to improve GLP-1 drugs beyond just weight loss.
1. Making the drugs easier to take to increase adherence
Over the last few years, GLP-1 medications have surged in popularity. Although the drugs were first approved to treat diabetes and weight loss, they have also shown benefits for cardiovascular health, inflammatory diseases, and cancer.
However, long-term adherence to the medication has been difficult, with data showing that around 50% of people who start a GLP-1 stop taking the medication within a year. Although high costs may play a role for some patients, the inconvenience of taking weekly shots and severe side effects also impact adherence.
So far, both Novo Nordisk and Eli Lilly have introduced new daily GLP-1 pills for weight loss to make dosing easier for patients. Currently, other companies are working on their own GLP-1 treatments that require fewer injections, which could reduce the burden on patients.
For example, Pfizer is testing a monthly GLP-1 injection that would reduce the total number of shots a patient needs from 52 per year with existing drugs to as few as 13, including a ramp-up dose. The company is planning to test the drug in over 20 clinical trials this year.
"Lowering the weight alone is the beginning," said James List, Pfizer's chief internal medicine officer. "Quality of weight loss is important.
Amgen is also testing a GLP-1 drug in combination with a monoclonal antibody that could potentially reduce the number of injections needed even further to just four to six times a year.
"Weight loss is incredibly important, but on top of that is living long-term with this disease and finding easy ways for patients to maintain their weight," said Susan Sweeney, Amgen's EVP for obesity.
2. Reducing the side effects associated with GLP-1 drugs
Gastrointestinal symptoms, such as nausea, vomiting, and constipation, are common with GLP-1 medications. Patients also reported several other side effects, including some that are more severe like gastroparesis or stomach paralysis, intestinal blockage, inflammation of the pancreas, and gallbladder damage.
To reduce the impact of GLP-1s on the gut, some companies are experimenting with dosing strategies, such as starting with a smaller dose before increasing it over time as a patient's body adjusts to the drug.
Other companies are testing how GLP-1 drugs work with amylin, a natural hormone produced in the pancreas. For example, Pfizer is planning to test its new GLP-1 drug with amylin in a clinical trial this year. Roche's Genentech, Eli Lilly, and Novo Nordisk are also all developing amylin weight-loss drugs.
According to Manu Chakravarthy, an SVP at Roche-Genentech, amylin doesn't slow down stomach emptying like GLP-1 drugs so it could help reduce feelings of nausea. Reducing stomach slowdown could also alleviate other gastrointestinal side effects.
"It gives you a feeling of satiation — satisfaction with your meal. It doesn't give you an aversion to eating your meal," Chakravarthy said. "It's a subtle but very important difference."
Advisory Board's weight-related resources
To help you address the growing use of weight management drugs, Advisory Board offers several resources:
- Guide to today's top obesity care trends
- Innovative solutions to today's obesity care challenges
- A candid conversation: Physicians on the front lines of GLP‑1 care
- 3 major trends shaping today's obesity care market
- 4 key elements of comprehensive obesity care
- Weight management and obesity care resource library
3. Protecting muscle mass during weight loss
Another side effect of GLP-1 drugs is unintended muscle mass loss due to rapid weight loss. This has made protecting muscle mass while targeting fat more precisely a key priority for drugmakers.
Recently, Boehringer Ingelheim released results from a Phase 3 clinical trial that showed patients on its experimental GLP-1 drug lost an average of 16.6% of their body weight over 72 weeks. Of the weight loss, 10.8% was lean mass, including muscle. In comparison, lean mass made up between 25% and 40% of weight lost with currently available GLP-1 drugs.
According to Boehringer Ingelheim, the results suggest that "weight loss was primarily driven by reductions in fat mass." Of the weight loss in the trial, 34% was visceral fat, which is found in the abdomen and can damage organs. In addition, 60% of patients who had metabolic fatty liver disease reduced their liver fat to normal levels.
However, 20% of patients in the trial stopped taking the drug due to side effects, something that patients and doctors will need to consider if the drug is approved in the next few years.
Currently, Eli Lilly and Novo Nordisk are the main players in the GLP-1 weight-loss market, but other drugmakers believe that the improvements in their own GLP-1 products will help them be competitive, even if they are entering later.
"The differentiation has to be clinically meaningful, and it has to fill a gap, and we think there are tons of gaps right now," List said.
Similarly, Neerja Balachander, Boehringer Ingelheim's VP of U.S. clinical development, said the company "continue[s] to believe [the weight-loss market] is going to be a big tent."
(Rowland, Washington Post, 6/10)
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