Yehuda Handelsman, MD, FACP, FNLA, FASPC, MACE: [There have been advancements] with the invention of more potent drugs that don’t cause hypoglycemia, namely the GLP1. SGLT2 inhibitors may not be as potent, but they’re potent enough early on in the disease without causing hypoglycemia. Now we can help. The medical society’s goal was always an A1C [glycated hemoglobin] of less than 6.5%. [That was the] official goal. On my patients, however, my goal has always been an A1C level of less than 6%, or as low as I can get them. I could never get them lower than 5% unless they’d institute lifestyle [changes]. If they’d institute lifestyle [changes], we could get a patient down to close to 5%, and not with medication. This has changed with high-dose GLP1 receptor agonists and high-dose fuse molecules such as tirzepatide. Right now they can get individuals to an A1C level of less than 5.7% without causing hypoglycemia. We’ve never seen that before. It will have to change our thinking going forward. With that, several bodies decided to define remission. Do you want to talk about it?

Jennifer B. Green, MD: There are 2 competing camps, to put it simply. One group that has devised the technically correct answer is that remission means there was an intervention given—a medication or a surgical procedure that achieved normal range of hemoglobin A1C or normal glucose levels on the medication. If it were withdrawn, then the person remained in a normal glycemic state. On the other hand, there’s an emerging group that’s pushing the concept of achievement of normal glycemia in and of itself, irrespective of the intervention that’s being used and that has been continued. That should qualify as diabetes remission too. There’s a bit of attention there.

In my experience, very few things would cause a person to achieve normal glycemia. If you discontinued [a medication] or you had no additional interventions, that would keep a person in the normal glycemic range. The exception would be bariatric or metabolic surgery. But from a medication perspective, that’s a bit challenging. There are small studies where individuals who had just been diagnosed with type 2 diabetes were treated very intensively with insulin therapy, sometimes with insulin pumps. Once the insulin therapy was stopped, they had diabetes remission. We just don’t know how long those effects last, and it’s probably not particularly long.

Yehuda Handelsman, MD, FACP, FNLA, FASPC, MACE: They were in remission for only a few months, and then it all came back. You’re correct. That’s why it was so funny that they defined remission at 3 months with an A1C level of less than 6.5%. I don’t want to say laughable, but that’s laughable because it won’t hold there. We always have a teaching moment. For a patient diagnosed with diabetes, I’d put them on a lifestyle change and at least a couple of medications. By 6 months [I hope to] get them from an A1C level of 9.5% to 6.25%. But by 1 year, many have gone back. They don’t adhere to medication, they don’t adhere to diet, and they don’t do what’s recommended long term. I never thought that we’d have to be that dogmatic and say, “Remission is this.” You cannot be in remission in a 6.3% A1C because you don’t have enough beta cells to compensate for what your needs are. If you stay at 5.4% for 3 years, you may build enough islet cells that you can be drug-free for a couple of years. Even among bariatric patients, in 3 to 5 years up to 50% return to diabetes again.

Jaime Murillo, MD: Do we have a magic pill? Or we haven’t gotten that yet?

Yehuda Handelsman, MD, FACP, FNLA, FASPC, MACE: You’re not going to pay for that [laughter].

Jaime Murillo, MD: Because you’re talking about tirzepatide or GLP1s. Is there such a thing as diabetes remission without a lifestyle intervention, or is that not conceivable yet?

Jennifer B. Green, MD: Some of these newer agents that are so effective in glucose lowering and promoting weight loss make it easier for the person to make effective lifestyle changes. Some of it is a drug effect, but some of it is the fact that individuals are less hungry and eat considerably less.

Yehuda Handelsman, MD, FACP, FNLA, FASPC, MACE: They think less of food.

Jennifer B. Green, MD: Yes, they think less of food. We achieve appropriate lifestyle changes much easier with these newly available medications.

Yehuda Handelsman, MD, FACP, FNLA, FASPC, MACE: In a couple of the studies, I’ve seen similarities with high-dose GLP1 and tirzepatide. They spelled it out. They took individuals who’ve had diabetes for 14 years, which we used to say was the end of the road, and [put them] on multiple insulin injections. They lowered A1C levels to less than 5.7%—50% of them with a reduction of insulin. It’s insane if you think about it. We never thought those patients had an insulin reserve. There’s much more that we can learn. We can’t allow older thinking hold us back. We’ll have to get used to that because we have more cases of obesity than overweight [in the United States]. You’re going to see more complications with insurance companies.

Eugene E. Wright Jr, MD: If we can’t allow older thinking to get in the way of this, can we imagine—

Yehuda Handelsman, MD, FACP, FNLA, FASPC, MACE: We shouldn’t allow.

Eugene E. Wright Jr, MD: We shouldn’t. OK. Can we have an opinion about starting these potent agents earlier? Maybe before they’ve got 10 years of diabetes behind them and they’re on multiple doses of insulin. When we’re using earlier treatment to get A1C [lowered], we know there’s a legacy effect that occurs with glycemic exposure over time. If we minimize that, we might make a significant improvement in some of these complications. We’re treating diabetes to prevent these.

Yehuda Handelsman, MD, FACP, FNLA, FASPC, MACE: That’s music to my ears because that’s how I’ve been practicing for many years. I’m glad guidelines now support you. I don’t think all guideline support what you just said, but medical information is coming out to support us more and more.

Transcript edited for clarity.