The following is the transcript from an onsite interview with Dr. Neil Skolnik and Dr. Hertzel Gerstein at the 79th American Diabetes Association Scientific Sessions held June 7-11, 2019 in San Francisco, California. The transcript has been edited for clarity.
Neil Skolnik, MD: I’m Dr. Neil Skolnik, and I am talking live from the 79th American Diabetes Association Scientific Sessions with Dr. Hertzel Gerstein, a Professor of Medicine at McMaster University, and a clinical trialist, who was one of the people announcing the landmark results of the REWIND trial. He was first author of the cardiovascular outcome part of that paper. Welcome, Dr. Gerstein.
Hertzel C. Gerstein, MD, MSc, FRCPC: Thank you very much, Neil.
Skolnik: This was a landmark paper because, unlike most of the cardiovascular outcome trials (CVOTs), which looked primarily at patients with existing cardiovascular disease, this looked at the type of population that we see in primary care every day: people without cardiovascular disease. Can you tell us a little bit about the population enrolled in this study?
Gerstein: Of course. In the REWIND trial, we specifically set out to recruit a group of people with type 2 diabetes who were representative of the types of people with diabetes seen in practice around the world. We recruited people with either newly detected diabetes or people who had established diabetes. There was no lower limit on the HbA1c, but there was an upper limit of 9.5%. We recruited people who had had a previous cardiovascular event and those who had not; those with previous cardiovascular disease and those without. We were able to recruit 9901 people from 24 different countries between 2011 and 2013, and we followed them for a median of 5.4 years. During that time, we collected cardiovascular events as well as other outcomes.
Skolnik: What was the average HbA1c?
Gerstein: There was no lower limit of HbA1c, and as a result, the average HbA1c of patients in our trial was 7.3%, and the median value was 7.2%. This means that half of our participants had an HbA1c at baseline that was
Skolnik: This is a lot lower than other CVOTs. Let’s now talk about the findings.
Gerstein: People who were randomly assigned to dulaglutide had a 12% lower hazard of the cardiovascular composite outcome, a base outcome of nonfatal MI, nonfatal stroke, or death from cardiovascular causes, compared to people who were randomly assigned to a placebo. The effect began to become apparent during the first year of therapy. And 2 event curves diverged and continued to diverge in a proportional fashion during the entire follow-up period.
Skolnik: Those are remarkable results. In addition, were there renal endpoints that were positive?
Gerstein: Yes, we prespecified renal outcomes. We knew that these patients would develop renal outcomes over this long period of time. The composite renal outcome was the first occurrence of clinical proteinuria or macroalbuminuria, a persistent eGFR decline by >30%, or chronic renal replacement therapy. When we looked at the effect on the composite, we saw that people allocated to dulaglutide had a 15% lower hazard of developing the composite renal outcome during follow-up, compared to people allocated to placebo.
Skolnik: Were there any other findings from the study?
Gerstein: Yes, even though people came in with a pretty good mean baseline HbA1c, we found that during >5 years of follow-up, there was a 0.6% lower HbA1c level in people who were on dulaglutide compared to placebo. Similarly, there was about a 1.5-kg weight loss during that time. And systolic blood pressure also went down modestly, between 1 and 2 mmHg.
The takeaway message here is that when you want to give a patient a drug that is good for managing their diabetes and has cardioprotective effects—effects that are durable without any other side effects—dulaglutide is a good choice.
Skolnik: Great information, Dr. Gerstein. Again, this is Dr. Neil Skolnik at the 79th American Diabetes Association Scientific Sessions for Univadis.
Neil Skolnik, MD is a Professor of Family and Community Medicine at Sidney Kimmel Medical College, Thomas Jefferson University, and Associate Director of the Family Medicine Residency Program at Abington-Jefferson Health.
Hertzel C. Gerstein, MD, MSc, FRCPC is a Director in the Division of Endocrinology & Metabolism, and a Professor in the Department of Medicine at McMaster University.