PracticeUpdate Diabetes Best of 2018

EXPERT OPINION 17

profile in patients with type 1 diabetes. Now, virtually every SGLT2 inhibitor com- pany has ongoing programs to test the use of their drugs in type 1 diabetes and there’s a lot of exciting early information to suggest similar benefits. Reductions in A1C, mod- est reductions in weight, that’s important. Blood pressure improvements, really the things we’re looking for to be used in addi- tion for insulin programs in our patients with type 1 diabetes. Dr. Sloane: Thank you. Speaking of advance- ments and exciting potential new therapies, I was wondering you’d be willing to comment on emerging therapies for type 1 diabetes, such as beta cell or islet transplantation and where we are with all of that? Dr. Leahy: Well, the hope, eventually, is to have a therapy which will cure the dis- ease. And to cure a disease where beta cells are gone you have to give them back. Whole pancreas transplantation has been around, really, since the ‘60s and ‘70s and continues to be a used therapy and pretty successful, frankly, but it’s a big deal. So, islet transplantation has really been the concept of something which might be technically easier, maybe a little easier from immunosuppression point of view. With information 20 years ago that sug- gested we were well along our way for successful islet transplantation and any- one who knows this field will know that we ran into some significant roadblocks includ- ing much less discussion about successful islet transplantation. That’s changed and there are, in fact, a number of centers around the world that are doing very successful islet transplants. But in many ways it’s still a very small ther- apy given the number of people with this disease and I don’t think one can easily look at it and think it can be expanded all that much because of the lack of availability of islets. That’s really our problem. So, what’s happened is that the field has changed to stem cell therapy. And we’ve talked about stem cell therapy for proba- bly 20 years, but within about the last 5 or 6 or 7 years stem cell therapy has hugely evolved to the point where many labora- tories around the world can reproducibly create pretty healthy beta cells from stem cells in a test tube and transplant them back into animal models. And we’re really at the doorstep of clinical trials, which will begin by using different kinds of stem cell approaches to do human trials and see where we end up. I think this is one of the most exciting things that’s ongoing.

" …but within about the last 5 or 6 or 7 years stem cell therapy has hugely evolved to the point where many laboratories around the world can reproducibly create pretty healthy beta cells from stem cells in a test tube and transplant them back into animal models, and we’re really at the doorstep of clinical trials… I think this is one of the most exciting things that’s ongoing "

with weight and metabolic disease, and in fact, one of the big observations in studies that are looking at teenagers with type 1 dia- betes and people in their 20s is there has been an evolving increase in terms of obe- sity and metabolic disease, hyperlipidemia, hypertension. All of the things we think about, so we’re beginning to think about drugs that might actually be used in type 1 diabetes in combinationwith insulin programs to bemet- abolic beneficial drugs and one of those classes of drugs are SGLT2 inhibitors. It turns out there’s a New England Journal paper from 2017, which is kind of a proof of principle paper, reporting on a drug called sotagliflozin. It is an SGLT2 inhib- itor, but it’s a very special drug because it’s not only an inhibitor of SGLT2, but it’s also an inhibitor in part of SGLT1, a very different transporter that’s in the gut, so it tends to lower postprandial glucose as a bit of an added benefit for these drugs. But what that paper showed was some weight reduction, a small reduction in levels of hemoglobin A1C, and a pretty good safety

of these drugs and reverse some of the problems and get people to a healthy liver? That’s still really early in the evolution of that data and part of it’s technical. I mean, in many ways, you can’t answer these ques- tions without proper technology, which is often biopsies, and those are complicated studies to do. So, I think, where we are right now is there is hope because we know they will lower liver fat that in the long run they will be use- ful drugs, but how we end up eventually targeting patients and using these drugs is still really an evolving issue. Dr. Sloane: Fantastic. We’ll have to keep an eye out for that. There’s also some discus- sion of potentially adding some oral agents to the treatment of people with type 1 diabe- tes. I was wondering if you would comment on the use of SGLT2 inhibitors and their utility and efficacy in treating type 1 diabetes along with insulin? Dr. Leahy: Well, this one is actually a fairly hot topic now. The reason, simply, is that like type 2, patients with type 1 diabetes struggle

Go to www.practiceupdate.com/c/70072 to watch this interview with Dr. Leahy.

VOL. 2 • NO. 4 • 2018