Side Effects of Anti-Diabetic Agents

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The MD Magazine Peer Exchange "Improving Management of Type 2 Diabetes Mellitus" features a panel of physician experts discussing current best practices to treating and managing patients with T2DM that generally includes lifestyle modifications as well as medication. The mechanisms of action, patient selection criteria, and side effects for various oral medication classes are included in the discussion.

This Peer Exchange is moderated by Peter Salgo, MD, professor of medicine and anesthesiology at Columbia University College of Physicians and Surgeons, and an associate director of Surgical Intensive Care at New York-Presbyterian Hospital.

The panelists are:

• Robert Busch, MD, director of clinical research in the Community Endocrine Group at Albany Medical Faculty Practice in Albany, NY
• Ralph DeFronzo, MD, professor of medicine and chief of the diabetes division at the University of Texas Health Science Center in San Antonio, TX
• Pamela Kushner, MD, clinical professor at UC Irvine Medical Center and director of Kushner Wellness at UC Irvine Medical Center in Los Alamitos, CA
• Jeffrey Miller, MD, professor of medicine and clinical director of the Division of Endocrinology and Diabetes at Jefferson Medical School in Philadelphia, PA

Peter L. Salgo, MD: We’re talking about these wonderful drugs, the SGLT2s, the DPP4s. They’re great, they’re this and they’re that. What are their side effects?

Robert Busch, MD: Well, as Dr. Miller said, DPP4s have very little side effects, but not as much efficacy. There are head-to-head studies with SGLT2 versus DPP4; the A1C is superior, drops with canagliflozins, and the others as well. Even comparing with sulfonylureas, they had better efficacy, but the ADA guidelines call SGLT2s intermediate-efficacy, not high-efficacy like a sulfonylurea. So, they inappropriately do that. In any event, the side-effect profile of DPP4 is pretty minimal. The side-effect profile of SGLT2s are more nuisance side effects.

Peter L. Salgo, MD: Like what?

Robert Busch, MD: Vaginal yeast infections in women, uncircumcised men can get balanitis or yeast infections—but you may actually have to talk to the patient. Take your head up from the computer and ask the woman, “How many times have you had yeast infections?” And if she said, “My last one was 20 years ago,” that’s not going to be as big a deal as someone who gets them five times a year and comes in on an antibiotic. So, you have to do clinical judgment, and most of these infections are one and done. Eighty percent are one-time events, easily treatable. The benefit to the patient—as we said, the blood pressure lowering and the weight loss—is the patient feels that right away. In fact, patients who’ve had a yeast infection want to stay on the medication after you treat them because of the other benefits of the drug. So, those are the main side effects. And, as Dr. DeFronzo said, in EMPA-REG, there is a pretty minimal side-effect profile.

Peter L. Salgo, MD: In all seriousness, without computer-generated data, to some degree, we’re out there in the ozone. We’re not compiling good flow sheets, we’re not following our patients. We don’t have a lot of data that’s just spewing forth onto the screen either, right? There is a use for computers, you’ll admit that.

Peter L. Salgo, MD: What I’d like to know is patient selection here. We’ve discussed these drugs. We’ve discussed a whole group of things.

Ralph DeFronzo, MD: Can I stop you for just one second?

Peter L. Salgo, MD: Sure.

Ralph DeFronzo, MD: Because we’ve talked about DPP4s and we talked about SGLT2. But there are other classes of drugs. So, another class of drugs that I think is very, very important are the GLP-1 receptor agonists. The unfortunate part is these drugs, although they preserve beta cell function on a long-term basis, they are good at weight loss, the side-effect profile is pretty good, and most recently, we’ve had at least an announcement that the LEADER study with liraglutide decreased cardiovascular events. This is a very important class of drugs. It’s very underutilized. Five percent of new prescriptions in the United States are for GLP-1 receptor agonists. So, I think there needs to be more education, more use of this class. I also am a big believer in the thiazolidinediones.