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June 25, 2021
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Improving diabetes care: A conversation with Silvio Inzucchi, MD

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For Silvio E. Inzucchi, MD, a simple question from a patient who underwent coronary artery bypass graft surgery would spur an interest in clinical research that helped lead to paradigm changing discoveries.

“[The patient] was prescribed metformin and a sulfonylurea for his type 2 diabetes, which was well controlled,” Inzucchi, professor of medicine at Yale University School of Medicine and Yale-New Haven Hospital, told Healio. “He asked me if I thought these medications were safe for his heart and if they might help him prevent future cardiac problems. I was embarrassed to say that I did not know the answer. This led to my now longstanding interest in the CV impact of glucose-lowering agents. The best ideas for investigation stem from actual patient conundrums.”

Inzucchi is a professor of medicine at Yale University School of Medicine and Yale-New Haven Hospital.

Inzucchi would go on hold leadership roles in several large clinical trials related to diabetes medications and their CV impact. One such trial, the landmark EMPA-REG OUTCOME, was the first of a series of CV outcomes trials demonstrating the significant CV benefit of SGLT-2 inhibitors for people with type 2 diabetes. The findings, along with data from similar trials that followed, ultimately led to new treatment guidelines.

Inzucchi is the recipient of the American Diabetes Association’s 2021 Outstanding Physician Clinician in Diabetes Award, which is presented to honor meritorious contributions to diabetes clinical practice. In announcing the honor, the ADA noted Inzucchi was instrumental in developing the now widely accepted concept of individualizing glucose-lowering therapy based on risks and benefits of therapy in the context of underlying patient characteristics. Inzucchi will receive the award during the virtual American Diabetes Association Scientific Sessions.

Healio spoke with Inzucchi his involvement with EMPA-REG OUTCOME, the potential of developing “designer” diabetes regimens for patients, and his family’s French bulldog, Tillie.

Healio: What is the defining moment that led you to your field?

Inzucchi: I am not sure there was a single defining moment. I was attracted to endocrinology because it is a specialty that is deeply embedded within internal medicine, that deals with some extremely common diseases, like diabetes, and allows practitioners to develop long-term relationships with patients. It is also a perfect field for those of us interested in medical education since internal medicine residents tend to see very little endocrinology in their training programs outside of the inpatient management of diabetes.

One episode early on in my career that spurred my interest in clinical research involved a patient who had been discharged from the hospital for recent abdominal surgery. He was furious that his diabetes, which he had worked so hard to control for so many years, was basically out-of-control during his entire post-op period. This made me ask the question, “Why can’t we do at least as well as patients do managing their diabetes once they are in our hospital?” This episode stimulated my longstanding interest in quality improvement in inpatient hyperglycemia management.

Healio: Have you ever been fortunate enough to witness or to have been part of medical history in the making?

Inzucchi: I have witnessed many advancements in endocrinology and specifically in diabetes care. I can recall when we only had sulfonylureas and insulin to treat diabetes. When metformin was introduced in the U.S. in 1995, that was a real game-changer. Not only did we have a drug that could lower glucose but not lead to hypoglycemia, but we also had something other than sulfonylureas, so these two classes could be combined. That concept, which now sounds quaint, was revolutionary at the time.

I have also witnessed the advent of many additional classes of glucose-lowering agents, including thiazolidinediones, SGLT2 inhibitors and GLP-1 receptor agonists. These drugs have markedly transformed the management of type 2 diabetes. Simultaneously, there have also been great advancements in diabetes technologies. These have made type 1 diabetes much easier to manage. I am still amazed by what our patients can do these days compared with when I started practicing in the mid-1990s — closed-loop insulin pump/sensor systems were but a dream at that time.

I have had the good fortune of being involved in several important clinical trials that have changed the way we practice diabetes medicine. The most well-known was EMPA-REG OUTCOME. I can still remember the look of shock in the eyes of the steering committee members when we were unblinded to the results of the trial in Mainz, Germany, just a few weeks before we presented the final data to packed crowd at the 2015 EASD meeting in Stockholm, Sweden. It was a real thrill!

Healio: What do you think will have the greatest influence on your field in the next 10 years?

Inzucchi: For type 2 diabetes, it is going to be more effective weight-loss agents that eventually may compete with the outcomes achieved by bariatric surgery. Also, greater insights into the heterogeneity of this disease, as well as its genetic underpinnings. Hopefully, one day we will be able to prescribe “designer” regimens for our patients to specifically address their individual pathophysiologic abnormalities.

In type 1 diabetes, clearly it is going to be mostly about better and better technologies. I am also hopeful that the very latest research on immuno-prevention will become well-established during the next decade. How cool would it be to identify very high-risk individuals, treat them with a single infusion and totally abrogate their progression to a life of insulin dependence?

Healio: What advice would you offer a student in medical school today?

Inzucchi: Being a physician is a great privilege. Work hard, study hard. Be skeptical. Ask questions. Never stop learning. Listen to your patients.

Healio: What are your hobbies/interests outside of practicing medicine?

Inzucchi: I have developed a love of French bulldogs. Our little Tillie is just the sweetest little thing. And this is from someone who grew up in the Bronx and never took much to animals at all.

Silvio E. Inzucchi's love of french bulldogs begins with his dog, Tillie. Photo courtesy of Silvio Inzucchi.

I am also an amateur mixologist and have developed several pandemic-inspired cocktails over the past year. I am told that the best are the “COVID Crusher” and the “N-95.” Readers can email me for the recipes.

Other joys include going out to our favorite steakhouse with my wife, watching my children succeed in life, University of Michigan football — although not very joyful over the past few years — and country music.