Are Older Diabetes Drugs Safe and Effective?

Jay H. Shubrook, DO; Allison M. Petznick, DO


December 22, 2017

Jay H. Shubrook, DO: Hi. I'm Jay Shubrook, DO, professor in the Primary Care Department at Touro University, California, and we are continuing our series Everyday Diabetes: Practical Management for Primary Care. Today, I am talking with Allison Petznick, DO, a family physician and fellowship-trained diabetologist at Northern Ohio Medical Center in Sandusky, Ohio.

Allison, welcome. We are glad to have you here today.

Allison M. Petznick, DO: Thank you.

Dr Shubrook: There are so many medicines used to treat diabetes today. The great majority of them are new. One of the questions I get asked is: What is the place for the older medicines? Where and when do you use them?

Dr Petznick: I definitely think there's a place for the older medications. One of the biggest things that I deal with on a day-to-day basis is the cost of newer medications. If you give a patient a medication and they can't afford it, they're not going to take no matter what you recommend. That's the situation in which I will usually use those older medications.

There are other specific reasons to use some of the older medications as well, but cost is one of the main concerns that I have when choosing a medication.

Dr Shubrook: When I think of older medicines, I'm thinking of metformin, sulfonylureas, maybe pioglitazone.

Dr Petznick: Correct. I tend to keep most of my patients with type 2 diabetes on metformin, because it helps to make them more sensitive to their insulin so they can take less. It also helps with some of the weight gain associated with some of the other medications. There was some evidence found for decreased risk for cardiovascular disease in the UKPDS (UK Prospective Diabetes Study),[1] as well as some potential decreased risk for certain cancers as well. It has a lot of added benefits, in addition to its role in diabetes.

When patients come to me and are already on sulfonylureas, it is really hard to get them off of them.

Dr Shubrook: What about sulfonylureas?

Dr Petznick: I try to avoid sulfonylureas most of the time, unless cost is the primary patient concern. They have a very high risk for hypoglycemia. Preventing hypoglycemia is my biggest fear and my biggest obstacle in treating diabetes.

The sulfonylurea that I really try to avoid is glyburide. It has many active metabolites, and it stays in a patient's system a long time, secreting insulin that is non–glucose-dependent for up to 6-10 weeks after use.

What I find is that when patients come to me and are already on sulfonylureas, it is really hard to get them off of them. I find a lot of patients have rebound hyperglycemia when I take them off of them, even if I don't think that the medicine was really working that well to begin with.

I do find some use for pioglitazone besides the cost issue, because there is some evidence that it can help with fatty liver disease. It will also make patients more sensitive to their insulin.

Dr Shubrook: Those are some good examples. This year at the European Association for the Study of Diabetes (EASD) meeting, there was a study presented that compared new versus old meds, called TOSCA.IT (Thiazolidinediones Or Sulphonylureas and Cardiovascular Accidents.Intervention Trial).[2]

Dr Petznick: The TOSCA.IT study was a study that looked at approximately 3000 patients with type 2 diabetes who were already on metformin but had failed to gain control with metformin alone. The study attempted to determine whether adding pioglitazone or sulfonylureas to metformin decreased the risk for cardiovascular events. The primary outcome looked at a composite of nonfatal myocardial infarction, all-cause mortality, nonfatal stroke, and unplanned coronary revascularization.

The study was stopped early (57 months) because there were not enough events. It seems that we are treating these patients fairly well with all of these other medications, and causing a lot fewer cardiovascular events.

There was no difference between pioglitazone and sulfonylureas in decreasing risk for cardiovascular events. Neither drug was associated with a decreased risk, nor were they associated with a very high rate of cardiovascular events. Compared with sulfonylureas, patients taking pioglitazone had a better and more sustained glycemic response as well as decreased risk for hypoglycemia.

Dr Shubrook: That is some useful information. It sounds like although the study had some challenges and was truncated, the results suggest that we could be adding these old medicines to metformin and there will not be an increase in cardiovascular events. There might be a benefit of pioglitazone over sulfonylureas in terms of sustained control.

Dr Petznick: Correct. It was interesting because this study did not find any increased risk for fractures or congestive heart failure with pioglitazone, which are both adverse events that we know can potentially occur with pioglitazone.

Dr Shubrook: I think when I look at that study, I feel much the same way that you do. The conclusion is that yes, we can still use these medications safely. We do have to be careful about the risk for hypoglycemia with sulfonylureas. I loved your point that when you stop a sulfonylurea, you have to have a plan to substitute or add before you subtract. If you just stop a sulfonylurea when you think it is not working, you are going to probably lose control over the glucose. Now that we are doing studies looking at cardiovascular risk with antidiabetes medications, it is good to know that, at least on the basis of current data, we're not seeing added risk nor added benefit, when we add it to standard of care.

Dr Petznick: Correct.

Dr Shubrook: If you had to tell your colleague one important point about the older medicines, what would you tell them?

Dr Petznick: They have been around for a long time. We've got a lot of evidence to support their use. Hands down, metformin is probably the safest and has the most added benefits out of any of the older medications. Pioglitazone is probably a close second in my opinion. Sulfonylureas can be utilized when cost is the main issue.

Dr Shubrook: You could still use them in a patient where that is the significant problem.

Dr Petznick: Correct, as long as you are paying close attention to risk for hypoglycemia.

Dr Shubrook: Thank you so much for your time today and your expertise. We appreciate you contributing to the program.

Dr Petznick: Thank you very much. I am pleased to be a part of this.


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