The Prospects of Semaglutide for Treatment of Type 2 Diabetes Patients

Thought LeaderDr. Jan WesterinkInternist-Vascular PhysicianUMC Utrecht

In this interview, News-Medical talks to Dr. Jan Westerink about recent studies into Novo Nordisk’s semaglutide and its potential benefits for Type 2 Diabetes patients, that he and Novo Nordisk collaborated on.

Could you provide more information on the background of the study and the main results that were observed?

For this study we conducted a post-hoc analysis of the pooled data from SUSTAIN 6 and PIONEER 6, two Phase 3 trials investigating the use of the glucagon-like peptide-1 (GLP-1) drug semaglutide in the treatment of patients with type 2 diabetes who were at risk for cardiovascular disease.

The post-hoc analysis was performed by combining data from the two trials with the Diabetes Lifetime-perspective prediction (DIAL) of cardiovascular risk model. A lifetime model is different from a more traditional 10-year risk model as it can estimate the time a patient has left without cardiovascular disease while at the same time taking into account the chances of dying from other causes. By adding known benefits from preventive lifestyle and/or medication we can estimate the absolute benefit from that intervention. So, instead of telling a patient that the risk will be 20% lower we can discuss life-years gained from an intervention.

This means I can tell a patient, for example, ‘You currently have 23 years to go without cardiovascular disease and if you start taking a glucose-lowering treatment with proven cardiovascular benefits, like semaglutide, as part of your standard care treatment plan, you could increase this by 2 years. Whether a patient is OK with this return on investment of 2 extra life-years free of cardiovascular disease, besides the effect on glucose and bodyweight, is part of the shared decision making.

What was the rationale/medical logic that underpinned this study?

In a recent global study conducted by Novo Nordisk, the global prevalence of cardiovascular disease and risk and its management in people living with type 2 diabetes was uncovered. The study found that 1 in 3 people with type 2 diabetes have established cardiovascular disease, of which 9 in 10 with atherosclerotic cardiovascular disease. Out of this group, only 2 in 10 people are receiving glucose-lowering treatment with proven cardiovascular benefits.
New guidelines for treatment of type 2 diabetes in patients with known atherosclerotic cardiovascular disease support the use of glucose-lowering treatment with proven cardiovascular benefits. When discussing initiation of such a treatment with a patient, it is important to be clear about the potential benefits of this intervention. Discussing risk, risk reductions, and hazard ratios can often feel abstract for a patient. To improve shared decision making, new ways of discussing CVD risk with our patients are needed.

Semaglutide was the drug utilized in the study, what is the drug used for and how does it work?

Semaglutide is an analogue of the naturally occurring hormone, glucagon-like peptide-1 (GLP-1). GLP-1 is a hormone that induces insulin secretion, and has numerous beneficial effects on vital organs, including the pancreas, heart, and liver. It is used to improve blood sugar control in adults with type 2 diabetes.

How was the post-hoc analysis conducted?

We conducted a post-hoc analysis using the data from SUSTAIN 6 and PIONEER 6, which compared semaglutide with standard of care for people with type 2 diabetes who were at risk for cardiovascular disease. These trials had shown that there was a beneficial effect on reducing the risk of cardiovascular disease for people with type 2 diabetes by taking semaglutide

The post-hoc analysis was performed using the Diabetes Lifetime-perspective prediction (DIAL) of cardiovascular risk model. The DIAL model was developed based on data from 389,366 people with type 2 diabetes in the Swedish National Diabetes Registry and externally validated across multiple geographical regions. It was specifically developed for use in people with type 2 diabetes for lifetime risk prediction of cardiovascular events as well as the years free from cardiovascular disease gained from an intervention.

To be more precise we used the baseline characteristics of all participating patients in these trials and calculated their individual estimated CVD-free life expectancy. We then combined these estimations with the hazard ratio (HR 0.76) for MACE from a recent study combining SUSTAIN 6 and PIONEER 6. These analyses were thus meant to show that gain in estimated CVD-free life expectancy is dependent on baseline risk and life-expectancy.

With regards to the results of the study, what is the significance of them?

These results are significant and important because cardiovascular disease remains the leading cause of disability and death in people with type 2 diabetes. The results of the post-hoc analysis have shown us that starting preventative medication can mean greater life benefits too, e.g. a larger return on investment. It is difficult to explain risk to patients and for many patients, the main focus needs to be enabling them to understand their risk and what they can do to reduce it, whether it be taking a glucose-lowering drug with proven CV benefits like semaglutide, blood pressure and lipid lowering medication or lifestyle interventions.

How could the results impact the lives of people with type 2 diabetes?

It is difficult to explain risk to patients and for many patients, the main focus needs to be enabling them to understand their risk and what they can do to reduce it, whether it be lifestyle interventions, improving their lower blood pressure or glucose and cholesterol levels as well as specific drugs like semaglutide.  By using the results, we can provide patients with more precise quantitative information, allowing shared decision making on when and whether to initiate an intervention and to improve compliance in the long run.

Current treatment guidelines tend to treat every patient the same while not all patients respond to the same treatments in the same way, and important for our analysis, with the same return on investment during a lifetime. By using lifetime risk models such as DIAL, we can find out a patient’s individual risk and personalise their treatment plan based in part on the patient’s preferences.

Where can readers find more information?

Free access to the DIAL model: www.u-prevent.com

About Dr. Jan Westerink

Jan Westerink studied medicine at Utrecht University (1997-2003). During his training as an internist-vascular physician, he carried out three years of doctoral research and obtained his doctorate in 2012 as a result of research focused on the harmful effects of visceral fat and the postprandial phase. Since 2013 he has been working as an internist-vascular physician at UMC Utrecht. He has a special interest in vascular diseases in patients with type 2 diabetes mellitus in both care and research.

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