A potential new treatment to reduce cardiovascular risk in type 1 diabetes

Living with type 1 diabetes (T1D) means paying attention to many aspects of health, including heart and blood vessel health. People with T1D can have a higher risk of heart and vascular complications over their lifespan. One important factor that can affect these risks is high cholesterol, especially low density lipoprotein (LDL) cholesterol which is often called “bad” cholesterol.

Currently, statin medications (e.g., atorvastatin aka Lipitor), which lower the production of cholesterol, are commonly prescribed to help lower cardiovascular disease risk. Statins are generally recommended for people with T1D over age 30 who have had diabetes for at least 10 years, and for all people with T1D over 40. Diabetes Canada recommends a goal of keeping LDL cholesterol below 2.0 mmol/L. Although statins reduce the risk of heart and blood vessel problems, including heart attack and stroke, they don’t completely eliminate it. 

There is, however, a need for additional studies and strategies specifically focused on people with T1D since current guidelines for those with T1D are based on research conducted on people without diabetes or people living with type 2 diabetes.

A newer option: PCSK9 inhibitors

One promising approach is the use of PCSK9 inhibitors, which are a recent class of injectable medications that support the removal of LDL cholesterol from the blood. When used in addition to statins, the PCSK9 inhibitors have the potential to lower LDL cholesterol levels more than when using statins alone and hopefully reduce cardiovascular disease in all people, including people living with T1D. 

In a large clinical trial published in 2017 that included over 27,000 people with a history of cardiovascular disease, of which few lived with diabetes, researchers added the PCSK9 inhibitor Evolocumab to ongoing statin treatment for one group and compared it to a control group taking statins and a placebo. 

On average, participants receiving Evolocumab had a 66% reduction in LDL cholesterol levels compared to before initiating the PCSK9 inhibitor and these levels remained relatively stable throughout the 2-3 year follow-up period. During this time period, approximately 10% of all participants experienced a serious cardiovascular event (stroke, heart attack, death from cardiovascular cause), but these events were less common in the group taking Evolocumab (9.8% vs 11.3%), indicating that the combination treatment provided added protection.

Researchers have now released the data specifically from the 197 participants that live with T1D (0.7% of all participants). The T1D group was slightly younger than the no diabetes group (58 vs 63 years old) with an average diabetes duration of 28 years.

Evolocumab greatly lowered cholesterol in T1D

At the beginning of the study, the participants with T1D had slightly higher cholesterol levels than participants without diabetes. However, their cholesterol level was still, on average, below the recommendations for the general population (under 2.6 mmol/L). After 11 months of treatment, LDL cholesterol levels in participants with T1D were on average 55% lower than prior to treatment, relatively close to the 60% reduction in the non-diabetes group. 

Fewer cardiovascular events in people with T1D treated with Evolocumab

After 2.5 years, 9.4% of participants in the T1D group taking Evolocumab experienced a serious cardiovascular event (e.g. heart attack, stroke), compared with 18.5% in the T1D control group.

Potential for greater protection in T1D

The researchers calculated a “relative risk” of having a serious cardiovascular event in the different groups and found that Evolocumab lowered the relative risk in people with T1D more than those without diabetes. This suggests that the treatment could be especially beneficial for people living with T1D.

More research is needed

It’s important to note that there are some doubts that all participants identified as having T1D actually have T1D, rather than T2D. Identification of T1D was done using a questionnaire and supported by insulin use, however many people with T2D also use insulin. The average age at diagnosis was 30 years old which is a high average for T1D. The study also did not collect data on insulin delivery methods, diabetes technology use, hypoglycemic events, or the use of adjuvant (non-insulin) medications, some of which are known to reduce the risk of cardiovascular events beyond their effect on blood glucose.  

What can people living with T1D do to reduce cardiovascular risk? 

Optimal glucose management is by far the best way to reduce the risk of cardiovascular disease for people living with T1D. Regular physical activity, good food quality, and optimal blood pressure also contribute. However, even with these measures, cardiovascular risk can remain elevated and additional cholesterol lowering treatments may provide benefits. While this study is not perfect, it does provide data specific to people living with T1D with a history of cardiovascular disease and it suggests that the addition of cholesterol lowering PCSK9 inhibitors to statin treatment provides a benefit of similar magnitude as for those without T1D.  

This study underlines the need for bigger and more comprehensive, specific studies on the prevention of negative cardiovascular outcomes for people living with T1D. Data from the BETTER registry in Canada shows that about 70% of people living with T1D are already receiving recommended medications to reduce cardiovascular risk, but there is still room for improvement in targeting cholesterol levels.

Get involved in research

If you live with T1D and want to contribute your lived experience to research, consider joining the BETTER registry! Your experiences can make a difference.

Join the registry now !

Reference:

• Kang YM, Giugliano RP, Ran X, Deedwania P, De Ferrari GM, George JT, Gouni-Berthold I, Paiva da Silva Lima G, Handelsman Y, Lewis BS, Ohman EM, Wang H, López JAG, Monsalvo ML, Sabatine MS, Leiter LA. Cardiovascular Outcomes and Efficacy of the PCSK9 Inhibitor Evolocumab in Individuals With Type 1 Diabetes: Insights From the FOURIER Trial. Diabetes Care. 2025 Sep 1;48(9):1512-1516. doi: 10.2337/dc25-0942. PMID: 40544474; PMCID: PMC12368373.