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GLP-1s: Beyond weight loss and diabetes

Unlocking their potential for myriad chronic conditions


Arpana Mathur, MD, MBA Executive Medical Director, Medical Affairs, CVS Health


Semaglutide and tirzepatide, the active ingredients in such medications as Ozempic/Wegovy and Mounjaro/Zepbound, have been proven to improve metabolic health. This class of medications increases insulin release, delays digestion, and decreases appetite. Their benefits for people with diabetes and obesity have been well documented – and so has the cost.

While these drugs initially were used for diabetes management and are now approved for weight loss, research indicates promising additional applications. The range of potential uses is varied, from reducing inflammation that may hasten cognitive decline to lowering the risk of major adverse cardiovascular events and treating kidney disease.


 Drug Name   Manufacturer  Phase  Indication 
 Efocipegtrutide  Hanmi   Pharmaceutical  Phase II  the treatment of non-alcoholic steatohepatitis (NASH)
 Rybelsus   (semaglutide)  Novo Nordisk   Pharmaceuticals  Phase III  the treatment of early Alzheimer's disease
 Efinopegdutide  Hanmi   Pharmaceutical/   Merck  Phase II  the treatment of non-alcoholic steatohepatitis (NASH) in   adults
 BI456906  Boehringer   Ingelheim/ Zealand   Pharma  Phase II  the treatment of non-alcoholic steatohepatitis (NASH)   and fibrosis
 Ozempic   (semaglutide)  Novo Nordisk   Pharmaceuticals  Phase III  the treatment of non-alcoholic steatohepatitis (NASH)
 Pemvidutide  Altimmune  Phase II  the treatment of non-alcoholic steatohepatitis (NASH)
 Zepbound   (tirzepatide)  Eli Lilly  Phase III  the reduction in the risk of major adverse cardiovascular   events in adults with obesity and established   cardiovascular disease or with risk factors for   cardiovascular disease
 Mounjaro   (tirzepatide)  Eli Lilly  Phase III  the reduction in risk of major adverse cardiovascular   events in adults with type 2 diabetes mellitus and   established cardiovascular disease
 Mounjaro   (tirzepatide)  Eli Lilly  Phase II  the treatment of non-alcoholic steatohepatitis (NASH) in   obese or overweight adults
 Firsocostat +   cilofexor +   semaglutide  Gilead Sciences  Phase II  the treatment of compensated cirrhosis due to non-   alcoholic steatohepatitis (NASH) in combination with   cilofexor and semaglutide
 Ozempic   (semaglutide)  Novo Nordisk   Pharmaceuticals  Phase III  the treatment of peripheral arterial disease in adults with   type 2 diabetes mellitus
 Rybelsus   (semaglutide)  Novo Nordisk   Pharmaceuticals  Phase III  the reduction of risk of major adverse cardiovascular   events in patients with type 2 diabetes and   cardiovascular disease
 Wegovy   (semaglutide)  Novo Nordisk   Pharmaceuticals  pending FDA approval  cardiovascular event risk reduction in overweight and   obese adults with established cardiovascular disease


Cognitive decline

Research suggests that the use of GLP-1s may reduce inflammation and promote neuronal survival in the brain, lessening the effects and progression of disorders such as Alzheimer’s disease and dementia.1, 2 Trials are currently being conducted and show promise for both people with diabetes as well as those without.

There is a known link between mid-life obesity and the development of later-life dementia.3 People who are overweight or obese face a greater risk of having dementia later. Preliminary research for those with type 2 diabetes shows that when obesity is treated earlier in life, the risk for dementia is lowered as well.4


Cardiovascular disease

In trials, semaglutide, liraglutide, and dulaglutide were found to reduce cardiovascular events by 25 percent among people with diabetes.5 One specific trial showed benefit in patients without diabetes, finding reduced cardiovascular events in obese or overweight patients who already had diagnosed cardiovascular disease. This is promising for the 20 million people in the United States with coronary artery disease, most of whom are overweight or obese.6 Survival rates after a heart attack also improved after GLP-1 administration.7

Nearly 90 percent of people enrolled in the study were taking a statin, so semaglutide may be positioned as an add-on therapy to statin therapy that could further lower overall cardiovascular risk.8


Kidney disease

Semaglutide was tested in a double blind, placebo-controlled trial that enrolled people with both type 2 diabetes and chronic kidney disease. The drug was evaluated along with normal standard of care treatments. The main study goal was to measure the time to first occurrence of persistent 50 percent or greater decline in eGFR, a measure of kidney function, the start of dialysis or a kidney transplant, or death from kidney disease or cardiovascular disease. Secondary goals include measuring the annual rate of change in eGFR and death from any cause.

The clinical trial was stopped early after an interim analysis found that the drug met pre-specified criteria for showing efficacy.9 The recommendation to stop the study came from an independent data monitoring committee and will allow further research to take place.


Liver-related conditions

Nonalcoholic fatty liver disease (NAFLD) is a condition in which fat builds up in the liver, replacing healthy tissue. Nonalcoholic fatty liver (NAFL) and nonalcoholic steatohepatitis (NASH) are types of NAFLD. To date, NAFLD is the most common liver disease, affecting up to 70 percent of patients with diabetes.10 Currently, there are no drugs available to treat it. Beyond their anti-hyperglycemic effect and the surprising role of cardio- and nephroprotection, GLP-1s have shown a significant impact on body weight and clinical, biochemical, and histological markers of fatty liver and fibrosis in patients with NAFLD.11 GLP-1s could be a valuable treatment for both diabetes and NAFLD.


Are GLP-1s wonder drugs? It’s too early to tell. While research is being conducted for these additional indications, the only conditions approved by the FDA are weight management and diabetes. But early results are promising for people with these chronic conditions, indicating that GLP-1s may have myriad potential applications. As the health care landscape shifts, these drugs may change how we treat chronic health conditions, leading to better health outcomes and improved quality of life. 


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