Originally developed to improve diabetic control, glucagon-like peptide 1 receptor agonists (GLP-1s) have emerged as a successful treatment for weight management, but their potential applications may extend much further.
Growing evidence suggests the introduction of GLP-1s in the management of multiple diseases and disorders could help reduce the lifetime burden of chronic diseases on the healthcare system and improve patients’ overall wellbeing, thereby benefiting insurers.
Studies show that this class of drugs can be used to treat heart failure, liver disease, anxiety and depression, neurodegenerative disorders, kidney disease, sleep apnea, and addiction disorders. GLP-1s may be poised to become an integral part of treating certain chronic diseases and could improve all-cause mortality rates. A meta-analysis of initial research showed that GLP-1s reduced the risk of major adverse cardiovascular events (MACE) in patients with type 2 diabetes (T2D) by 14%, all-cause mortality by 12%, hospital admissions for heart failure by 11%, and the composite kidney outcome by 21%.1
In March 2024, the US Food and Drug Administration (FDA) approved Wegovy (semaglutide) for adults with cardiovascular disease (CVD) and either obesity and overweight to reduce the risk of cardiovascular death, heart attack, and stroke.2 Semaglutide, liraglutide, and tirzepatide have all shown cardiovascular protective effects, such as reducing lipid and blood pressure levels. Notable findings include:
Figure 1: Effect of once-weekly tirzepatide, compared with semaglutide, on lipid profile5
GLP-1s are also being investigated for the prevention and treatment of heart failure. There are currently no approved targeted therapies for left ventricular ejection fraction (EF)-preserved heart failure (HFpEF) associated with obesity. The SELECT trial of nearly 18,000 individuals showed that 2.4mg of semaglutide reduced heart attacks, strokes, and mortality due to CVD, with 73% fewer patients progressing to diabetes compared to the control group. Key findings included:
Insulin resistance is a common feature in neurodegenerative disease, and research shows that T2D is a risk factor for Alzheimer’s disease (AD) and Parkinson’s disease (PD). In addition to reducing insulin resistance, GLP-1s can reduce neuroinflammation and subsequent motor and cognitive impairment in patients suffering from neurodegenerative disorders, such as PD and AD.
Trials of lixisenatide in persons with PD have found the treatment improved non-motor symptoms, mobility, and quality of life, but longer and larger trials are now needed to determine the effects and safety of lixisenatide in persons with PD.7
Exenatide is the most prevalent GLP-1 in clinical trials for AD and PD treatments. A phase 2 trial of exenatide in treating AD showed that patients displayed reduced amyloid-β 42 concentrations, the abnormal accumulations that are a primary driver of AD. In a separate trial of 62 patients with moderate-severity PD, exenatide had positive and sustained effects on motor function after 12 weeks.8
The EVOKE phase III trial is studying the effect of semaglutide in AD, with preliminary results due in September 2025. Additional clinical trials are in progress, including the investigation of GLP-1s to treat glaucoma, Friedreich ataxia, and multiple sclerosis.7
One unexpected finding in GLP-1 users has been a reduction in alcohol consumption and addictive behaviors. This may be related to the impact on the brain’s reward system, as GLP-1s are expressed in areas of the brain influenced by addictive drugs, such as nicotine, opioids, and alcohol. The brain’s reward system triggers the release of dopamine, but this response is muted in the presence of drugs such as semaglutide.9
Studies to date have shown that semaglutide, liraglutide, and dulaglutide can reduce alcohol consumption and combat addiction. In one study of over 83,000 patients, semaglutide was associated with a 50%-56% lower risk for both incidence and recurrence of alcohol use disorder over a 12-month follow-up compared with other anti-obesity medications.10
Ongoing trials are currently studying semaglutide and tirzepatide for alcohol use disorder, semaglutide for opioid use and cannabis use disorder, liraglutide for opioid use disorder, and semaglutide and exenatide to achieve smoking cessation.9
Diabetic patients treated with tirzepatide, semaglutide, dulaglutide, and exenatide are less likely to be diagnosed with depression and anxiety. A recent study using 233 million patient records found significantly lower depression and anxiety scores for patients that were treated with GLP-1s, particularly with tirzepatide.11
Figure 2: The likelihood of patients being diagnosed with depression after a GLP-1 prescription compared to those on a non-GLP-1 medication11
Initial studies on the risk of suicide in individuals taking GLP-1s indicate that these drugs may increase suicidal thoughts and ideation. However, in a retrospective study of nearly half a million patients, semaglutide was associated with lower risk for incident (HR = 0.27) and recurrent (HR = 0.44) suicidal ideation compared with non-GLP-1 anti-obesity medications.12 A separate study of people with T2D treated with GLP-1s found the rate of suicide attempts was more than 53% lower in the GLP-1 group compared to patients treated with DPP-4 inhibitors (oral hypoglycemics).9
Diabetes is a known risk factor for acute kidney disease (AKD), which is associated with the risk of end-stage kidney disease and mortality. Trials to date have shown that GLP-1s may have beneficial effects on kidney function, especially relevant for T2D patients with chronic kidney disease (CKD).13
GLP-1s have been investigated for their impact in reducing the risk of obesity-related cancers (OACs) such as colorectal cancer, esophageal, breast, colorectal, endometrial, gallbladder, stomach, kidney, ovarian, pancreatic, and thyroid cancer, as well as hepatocellular carcinoma, meningioma, and multiple myeloma. In a study of more than 1.6 million patients with T2D and no prior diagnosis of OACs, patients treated with GLP-1s had a significantly lower risk for 10 of the listed cancers.16
Figure 3: Risk of OACs in patients on GLP-1s versus patients on insulin
GLP-1s, initially developed to help manage and treat diabetes and later used to treat obesity, are now showing significant potential to help prevent and treat CVD, mental health disorders, liver and kidney disorders, neurodegenerative disorders, addiction disorders, and cancer. Studies have shown improvements in CVD and all-cause mortality in diabetic patients on GLP-1s. Additional clinical trials are required to evaluate the efficacy, safety, and tolerability of the different GLP-1s for disease management and for reducing cause-specific and all-cause mortality.
This research could have significant implications for the life and health industry. Insurers should carefully monitor these trials and consider GLP-1s’ potential impact on disease incidence, prevalence, and mortality outcomes in the future.
RGA life and health insurance experts are actively engaging with insurers to help determine optimal paths forward in addressing GLP-1 challenges and other emerging issues. Ready to join the conversation? Contact RGA.
