This transcript has been edited for readability.
On the Endocrine Society meeting, I had the privilege of debating Dr Andy Ahmann about whether or not individuals with type 1 diabetes ought to be taking SGLT2 inhibitors. Now, that is truly one thing I’ve carried out for a very long time off-label as a result of I do know it helps a few of my sufferers with sort 1 diabetes obtain higher glycemic management. However I’ve additionally been very concerned with discussions in regards to the threat for diabetic ketoacidosis (DKA).
I used to be requested to current the con facet of utilizing SGLT2 inhibitors in individuals with sort 1 diabetes, and Andy talked about why we should always [use them]. I’ll give Andy’s facet first.
Cut back Unpredictability, Variability, and Misery
Mainly, the explanation to make use of SGLT2 inhibitors in individuals with sort 1 diabetes is that they assist sufferers obtain higher glycemic management. But it surely’s not that their A1c goes from 8 to six. What I see and what my sufferers have instructed me is that it helps cut back among the unpredictability and variability of their numbers, which helps cut back their diabetes misery and makes them really feel prefer it’s considerably simpler to handle their diabetes. You do, on common, see an A1c discount within the vary of 0.3%-0.6%. You additionally see some weight reduction, though it is not a lot; it might be on the order of 1-3 kg. Clearly, there’s a patient-driven want to make use of these brokers as a result of it makes them really feel higher and it helps them handle their diabetes.
Andy talked about the true, overarching causes to make use of these brokers, and so they actually need to do with their nonglycemic results. We all know that SGLT2 inhibitors in type 2 diabetes and in individuals with out diabetes have a marked profit when it comes to renal dysfunction. They assist sufferers with proteinuria decelerate their development to end-stage renal illness. We additionally know that these brokers are very useful in individuals with heart failure and assist forestall hospitalizations for coronary heart failure.
He would argue that you must use these brokers in individuals with sort 1 diabetes who’ve these high-risk traits. Frankly, if I’ve a affected person with sort 1 diabetes who has proteinuria and who’s actively working with me to handle their illness, including an SGLT2 inhibitor is sensible when it comes to serving to them gradual development of their nephropathy.
Threat for DKA Cannot Be Eradicated
My facet of the argument is that I am unable to remove the chance of sufferers growing DKA on these brokers. In each one of many scientific trials, there was an elevated threat for DKA when handled with an SGLT2 inhibitor in individuals with sort 1 diabetes in contrast with these within the management group. These medicine do improve the chance for DKA.
In Diabetes Spectrum, we lately published an inventory of the totally different protocols used to assist cut back the chance in our sufferers, however none of those protocols have been studied in a scientific means. Within the scientific trials of SGLT2 inhibitors in individuals with sort 1 diabetes, efforts to assist mitigate this threat had been variable and did not appear to me to essentially do the correct factor. They did not present sufficient affected person schooling or sufficient follow doing ketone testing. There’s quite a bit that I feel we have now to do with a view to select the correct sufferers.
Furthermore, I’m very frightened that if these medicine are accepted to be used in sort 1 diabetes, the unsuitable sufferers can be began on them, which means the sufferers who’re doing the worst, who aren’t taking sufficient insulin, and who could also be ketotic at baseline.
The usage of these brokers actually must be reserved for sufferers who’re testing their sugars, who should not ketotic at baseline, and who’ve an A1c that’s at the least fairly managed; I exploit a cutoff of 9%. I actually need a affected person who’s working with me who I do know may be taught to check their ketones if wanted.
Additionally, sufferers will need to have entry to medical care as a result of they’ll develop euglycemic DKA, which is DKA with comparatively regular glucose ranges. The way in which to eliminate the DKA — the ketones — is to have the affected person take extra insulin. Usually, glucose ranges aren’t terribly excessive in these people, so I’ve them devour carbohydrates to allow them to take extra insulin and eliminate the ketones. Clearly, I’ve them devour fluids to eliminate the dehydration. I actually need sufferers who I work with carefully with a view to really feel protected utilizing these brokers, significantly as a result of they’re getting used off-label.
FDA Approval Will Imply Extra Regulation
Ultimately, I feel Andy and I agree. We agree that there is a profit for our sufferers with sort 1 diabetes — to a point a glycemic profit, maybe extra when it comes to results on nephropathy and coronary heart failure. These research have to be carried out or we’ll simply need to extrapolate from research in individuals with sort 2 diabetes and in these with out diabetes.
I feel we each agree you can’t utterly remove the dangers. It might be good if some kind of protocol had been studied in a potential method to see how a lot threat discount we are able to see.
Hopefully, sooner or later, the FDA will really feel comfy approving these brokers, partly due to the advantages I’ve mentioned, but in addition as a result of if the FDA approves it, then there’s going to be extra regulation. There can be extra schooling, and possibly it may be coupled with prescriptions from the pharmacy for ketone take a look at strips.
I do not know precisely what sort of monitoring we would do if these medicine change into accessible for individuals with sort 1 diabetes. I might hope that by approving this class of medicine for individuals with sort 1 diabetes, we’ll be capable of make them even safer to make use of. Frankly, persons are utilizing them now, so why not make it one thing that is allowable and attempt to use them as safely as doable?
This has been Dr Anne Peters for Medscape. Thanks.
Anne L. Peters, MD, is a professor of medication on the College of Southern California (USC) Keck Faculty of Drugs and director of the USC scientific diabetes packages. She has printed greater than 200 articles, opinions, and abstracts, and three books, on diabetes, and has been an investigator for greater than 40 analysis research. She has spoken internationally at over 400 packages and serves on many committees of a number of skilled organizations.