Type 2 Diabetes Management: Choosing the Best Therapies
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Anne L. Peters, MD; Eleuterio Ferrannini, MD, PhD

Disclosures

October 09, 2015

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An Explosion of New Diabetes Treatments

Anne L. Peters, MD: Hi. I'm Dr Anne Peters. I'm here today with Dr Ele Ferrannini, who is a professor of medicine at the University of Pisa. Today we are going to tackle the difficult question of how to synthesize all that is new in the treatment of diabetes and how to make it practicable.

Why don't you tell us what your perspective is, an overview of what we have for treating diabetes that has come up in the past few years?

Eleuterio Ferrannini, MD, PhD: I think what is really striking about diabetes is that over a relatively short period of time, a number of new drugs and approaches have become available, whereas previously, the treatment and management of diabetes was essentially in a phase of stagnation. This is in contrast to what has been seen with hypertension, where there has been a steady development of new drugs over the course of time.

The other thing that is interesting is that there are multiple targets. It's not just the glucose or the glycated hemoglobin (A1c), but it's also the weight, the prevention of hypoglycemia, and correction of the basic pathophysiologic defects in diabetes. On the one hand, this should not be too surprising because we know that diabetes is a systemic, multifactorial, and polygenic disease. It makes all the sense in the world that there should be multiple therapeutic targets.

The difficulty for physicians is that all of these approaches have become available over a relatively short period of time. Although I believe that, in the long term, it will turn out to be an advantage and an asset, it may initially be confusing because doctors may have some difficulty finding the best treatment for the individual patient with so many options open.

Dr Peters: Yes. I think another thing that makes it confusing is that not only are there all the classes of drugs, but there are different names within the classes for each agent. Then, there are all of these combinations that all have their own names. Everything varies from once a day to once a week to oral to injected. I think it's very important for practitioners to start to understand the classes themselves and then how they will mesh together.

Choosing a First and Second Agent

What is your primary goal? When you have a patient with type 2 diabetes whose A1c is 9% or 10% and he is 45 years old, what do you think of when you start therapy?

Dr Ferrannini: The first thing that I do is gather as much information about this patient as I possibly can:

  • How did he learn about his diabetes?

  • How long has he been diabetic?

  • Is there a family history of diabetes?

  • What is his blood pressure?

  • What is his serum lipid profile?

  • What is his renal function?

  • Is there any history of allergy or intolerance to other drugs?

  • What is his family situation, not just the socioeconomic level, but the family?

Once I have compiled all of this information, I start thinking about informing the patient about diabetes. He may already know a lot but have prejudices or false ideas about it. Maybe he has been on the Internet and has found some strange things about this drug or that drug, etc. I think it's crucial these days that the information that is available is accurate, supported by evidence, and given at the very first contact with the patient before getting into the conversation about possible therapeutic options and what best fits his stage of diabetes.

Dr Peters: Do you tend to always start with metformin?

Dr Ferrannini: I think I would do that if it hasn't already been given to the patient. You cannot expect anything bad from metformin except for intolerance, in which case you stop it. Otherwise, according to reasonable recommendations, you are going to see this patient again within 3 months at most, and if metformin was not sufficient, then you have a number of options. I think that is quite reasonable.

Dr Peters: We talk about all of the choices at the second step. It's the step where everybody seems to get confused, partly because the guidelines make it clear that there is not one specific way to choose. Everybody is practicing in a different setting. Patients have different preferences. When you are treating somebody and choosing the second step—let's just say that cost isn't an issue, you can use any step that you want, and renal function is normal—what kind of next step do you tend to follow?

Dr Ferrannini: I think that there is sufficient power in terms of efficacy and safety in the different classes of oral agents such that I wouldn't mind trying an oral combination, either on top of metformin or in triple combination, because we know that the dipeptidyl peptidase-4 (DPP-4) inhibitors are very well-tolerated drugs. We know what to expect from them. We know that they're weight-neutral. They by themselves don't cause hypoglycemia, so we can go for those.

The glucagon-like peptide-1 (GLP-1) receptor agonists have pretty much the same profile, but they are injectable, so it may not go along with the preferences of the patient.

Now we have the sodium glucose cotransporter 2 (SGLT2) inhibitors, which can be combined with anything and everything simply because of the completely different mechanism of action. We have a good chance of benefiting on the side of weight control, avoiding hypoglycemia, and lowering blood pressure, which is in the range of the effect that you would see with an antihypertensive drug. Again, it depends on whether the patient is hypertensive or not. I don't think it would be unreasonable to try an oral approach first.

Dr Peters: That makes sense. There is often pushback in terms of injections, although with the once-weekly GLP-1 receptor agonists, my patients don't seem to mind them. Some of the techniques where you don't actually have to see the needle make it a lot easier.

Dr Ferrannini: Yes. I forgot to mention, Anne, that one thing that is new and that has happened because of this increased availability of tools is that the therapeutic armamentarium for type 1 diabetes is expanding. I find that of special interest because type 1 diabetes treatment has been insulin, insulin, insulin, insulin, and now we have better insulins and different insulins. The insulin treatment as a science and as a concept is being revisited and rediscovered.

There are also emerging data that some of the new drugs that were developed for type 2 diabetes may show benefit in association with insulin in type 1 diabetes. For the diabetic population at large, this is definitely progress.

Dr Peters: Yes. For everybody with diabetes, this explosion of new technology and treatments is making life easier and better, although maybe more complicated.

Is it sufficient to say that your choice of an agent—going back to type 2 diabetes—would be something that doesn't cause hypoglycemia, doesn't cause weight gain and ideally causes weight loss, and is relatively simple such as a pill once a day or an injection once a day or once weekly?

Dr Ferrannini: Yes.

Don't Fear the Insulin

Dr Peters: When you move on to insulin in a type 2 diabetic, how do you start treatment?

Dr Ferrannini: I think the experience and data that I have accumulated over the past 5 years do show quite convincingly that basal insulin is an advancement over whatever we had previously. This obviously explains why there are similar basal insulins being developed at a faster rate, which would be confusing to some colleagues but will be an advantage because there will be more options available. Again, I think the science of insulin treatment has improved.

Dr Peters: I tell practitioners to never be afraid of the next step. Each time I see patients, it's often because somebody—they or the practitioner—didn't want to start the insulin or advance the therapy. I think that we need to really encourage people to not wait because if you have an A1c of 8%, it's much easier to get it to target if your target is less than 7% than if you wait until the A1c is 9%.

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