How GLP-1 Therapies Are Transforming Health Care and the Future of Care Delivery

Few classes of medicines have moved as quickly from specialty treatment to widespread public awareness as glucagon-like peptide-1 (GLP-1)–based therapies. Although these medications have primarily been used to improve blood glucose control in people with type 2 diabetes, their role has expanded dramatically as newer agents have demonstrated substantial effects on weight loss and benefits across multiple organ systems.

That evolution is changing more than prescribing. As indications expand and new formulations and combinations emerge, GLP-1–based therapies are affecting how clinicians manage chronic diseases, how specialists work together, and how health systems think about cost and access.

“This is one of the most transformative medications of our time,” said Josephine Li, MD, clinical director of the Massachusetts General Hospital Diabetes Center and assistant professor of medicine at Harvard Medical School. Li is also the faculty lead for the HMX GLP-1-Based Therapies: Mechanisms of Action, Development, and Clinical Impact short course.

She added, “What’s really amazing and different is that GLP-1s are a class of medicines that have multi-system benefit and efficacy.”

From Glucose Control to Multi-System Therapy

Despite their recent prominence, GLP-1 receptor agonists are not new. The first was approved in 2005, and endocrinologists have used the drug class to treat type 2 diabetes for more than two decades. What has changed is both the effectiveness of newer agents and the understanding of what these medicines can do.

Earlier diabetes therapies were largely “glucocentric,” Li explained. Their principal goal was lowering blood glucose, sometimes with trade-offs such as hypoglycemia or weight gain. GLP-1–based therapies have helped shift that approach. In addition to improving glucose control, she noted, GLP-1 medications can promote weight loss, reduce the risk of cardiovascular events in patients with existing cardiovascular disease, and provide kidney benefits. 

The expanding indications are also changing who needs to understand these drugs. Diabetes and obesity do not fit neatly within specialty boundaries, and patients taking GLP-1–based therapies may be seeing primary care physicians, endocrinologists, cardiologists, nephrologists, dietitians, and other health professionals.

“These medications are forcing us out of these specialty areas,” Li said. In her own practice, she frequently finds herself communicating with a patient’s cardiologist or nephrologist or connecting patients with a dietitian. “There needs to be communication across the care team.” 

At the same time, the choices available to those care teams are multiplying. Dual agonists targeting GLP-1 and GIP have been followed by the development of drugs targeting additional metabolic pathways. Researchers are investigating triple agonists, combinations involving amylin, strategies intended to preserve muscle during weight loss, and additional oral therapies. 

“I think we’ll have even more options,” Li said. She expects oral therapies to become increasingly important, in part because some patients prefer taking a pill to an injection. 

More options do not necessarily make treatment simpler. Patients vary considerably in how much weight they lose, and in the side effects they experience. Li studies pharmacogenetics in hopes of eventually helping clinicians predict who will respond particularly well—or poorly—to a given therapy. Research has identified genetic variants that may influence response, but the evidence is not ready for routine clinical use. Treatment today still involves considerable trial and error.

There are other unanswered questions, including the effects of decades-long use and treatment in populations underrepresented in clinical trials, such as children with obesity, pregnant women, and patients with advanced kidney disease.

The changing clinical landscape may ultimately require health systems to rethink how they organize care. Li noted that some institutions are developing multidisciplinary cardiovascular and metabolic centers as specialists increasingly co-manage patients receiving these therapies.

“That infrastructure—that’s not traditionally how we practice,” she said. “But I think it’s increasingly necessary.”

A Clinical Breakthrough Meets an Affordability Challenge

Having an effective therapy, however, does not mean every patient who could benefit can get it.

For Benjamin Rome, MD, MPH, assistant professor of medicine at Harvard Medical School and a primary care physician and health policy researcher at Brigham and Women’s Hospital, the central obstacle is straightforward: cost. Without insurance coverage, patients may face hundreds of dollars in monthly out-of-pocket costs. Rome is also the faculty lead for the HealthXcelerate GLP-1-Based Therapies: Cost, Coverage, and Access for Transformative Drugs course.

The number of people potentially eligible for treatment magnifies the problem. Unlike some expensive therapies that treat small patient populations, GLP-1–based medicines target extremely common chronic conditions. As indications expand, the number of patients who might benefit could grow further.

That makes the distinction between value and affordability particularly important. A treatment can deliver meaningful health benefits without being affordable enough for an insurer or health system to provide it to everyone who meets the clinical criteria.

There is an argument that better health could eventually offset some of the expense. GLP-1 therapies can improve conditions that otherwise require substantial health care resources, including diabetes, cardiovascular disease, and kidney disease. However, Rome cautions against expecting those savings to cover the drugs’ current costs.

“So far, studies have shown that the savings from better controlling patients' diabetes and obesity won’t come anywhere close to matching how much is being spent on these medicines,” he said. 

Insurers also may not be in a position to wait decades for potential savings. Commercial insurers typically make decisions over relatively short budget horizons, while patients move between employers and insurance plans and eventually to Medicare. The payer covering a medication now may not be the one that benefits if the treatment prevents costly health problems years later. 

For patients, those financial calculations can translate into interrupted treatment. Rome has seen patients stop GLP-1 therapy when their insurance changed or because they could no longer afford it.

“We need to make sure that cost is not a barrier to access, so that patients are making informed clinical decisions not based on the cost of the treatment,” Rome said. At present, however, he acknowledged that affordability inevitably influences some patients’ decisions. 

Understanding the Entire GLP-1 Ecosystem

These access challenges are unlikely to disappear as the science advances. Instead, new drugs and indications may make decisions about pricing, coverage, and who should receive treatment more consequential.

Rome believes understanding those pressures is important beyond the health policy world. Pharmaceutical manufacturers, insurers, pharmacy benefit managers, clinicians, and policymakers approach GLP-1 therapies from different perspectives, and the incentives facing one group can affect the decisions made by another.

“There’s a lot of finger-pointing in the system,” Rome said. Rather than placing responsibility on a single participant, he argues for a broader look at how pricing and coverage interact. One central question is what price would make these therapies more widely accessible. 

That issue could become even more complicated as new therapies reach the market, and older drugs eventually face lower-cost competition. Clinicians and health systems may need to weigh the incremental benefits of newer treatments against less expensive alternatives, while policymakers and payers wrestle with how to expand access without making spending unsustainable.

For health care professionals, the rapid evolution of GLP-1–based therapies therefore matters well beyond any single specialty. Clinicians will have more treatment options and more patients taking these medications, while health systems will face tougher questions about how to deliver and pay for them.

The future of GLP-1–based therapy will depend not only on what the next generation of medicines can do. It will also depend on how effectively clinicians, health systems, industry, payers, and policymakers turn those advances into care that patients can access and sustain.