Early Combination Therapy in Type 2 Diabetes

Peter Salgo, MD: We have some strategies to overcome some of these delays in initiation. Your strategy is to talk about it early on. We talked about it early on. What else? You guys clearly have some other pearls.

Julio Rosenstock, MD: We also need to tell them that studies have shown that the insulin works well because we have a support system. We have the study coordinators that are pushing the titration, and then you have to do a systematic titration. You start with 10 units, which is totally nonthreatening. If you even are threatened by 10 units, you can start with 8 units. But the point is, they need to continue titrating and we need to empower the patient to do it. We need to make it very simple. For instance, we tell people that once they are comfortable checking the blood sugar in the morning and once they are comfortable taking the insulin, we tell them if the blood sugar is above 100 or 110 to take 1 extra unit per week, or 2 units per week. And they can go slowly, gradually titrating. Titrating is key. If they don’t do it systematically, the basal insulin won’t work.

Vivian Fonseca, MD: There’s actually a study that was done comparing patients who did it themselves, and physician offices directed titration. And the patients did better.

Peter Salgo, MD: Is titration the same as therapeutic intensification?

Carol Wysham, MD: No.

Julio Rosenstock, MD: No, that’s a different thing.

Peter Salgo, MD: What is that? Define that.

Julio Rosenstock, MD: No matter what, 50% or 55% are not going to get the targets that you have chosen with the patient. At one point, you need to advance the basal insulin. The thing that we have been doing wrong all these years is that we have advanced by using prandial insulin before each meal, or basal bolus and so on. That is way too much work for the patient. It is way too much work for the practicing physician. The way to go is when it’s time for “intensification.” I don’t like intensification. I know that you are an intensivist and you like that word, but I don’t like intensification. I like advancing therapy. When you want to advance therapy, I think that you need to use a GLP-1 (glucagon-like peptide 1) receptor agonist.

Vivian Fonseca, MD: Your question is a little broader though. It’s not just on insulin, it’s with adding on any additional therapy.

Peter Salgo, MD: Yes.

Vivian Fonseca, MD: There’s a different concept that is not been widely tried, which is using multiple drugs very early all together. And if you think about diseases like TB (tuberculosis) and HIV, we use combination therapy right from the start because we understand the concept of microbial drug resistance. But the same thing applies when you have a pathophysiology of a disease that doesn’t do well with only 1 or 2 drugs.

Julio Rosenstock, MD: You use metformin and SGLT2 (sodium-glucose co-transporter-2) right from the beginning.

Peter Salgo, MD: Tell me about the American Diabetes Association, American Association of Clinical Endocrinologists (AACE), and the American College of Endocrinology Guidelines. What do they say about this intensification?

Vivian Fonseca, MD: What they say is not totally wrong, if you follow their language, which says every 3 months, you should move ahead. The trouble is people take longer.

Carol Wysham, MD: The American Diabetes Association really does promote stepwise use—metformin, 1 of 6 medications as a second-line therapy. If they aren’t at goal in 3 months, go and add a third-line therapy and, eventually, insulin.

And then as far as the AACE, they state that if a person’s A1C is more than 1% above their goal (they set a goal of less than 6.5%, so they say if it’s 7.5% or greater), they should start with 2 therapies. And that’s absolutely right because we know that we do not get more than 1%. We don’t even get a 1% reduction. If you’re starting a patient with an A1C of 7.3% or 7.4%, you’re not going to get down to less than 6.5%. If your goal is 7%, you start at 8%. You’re not going to get there with 1 drug. So, absolutely, doing multiple drugs at the same time will help to get the patient to goal, and studies show combination therapy, from the beginning, has a greater chance of getting patients to goal than doing stepwise therapy.

Transcript edited for clarity.