COMMENTARY

Using Newer Diabetes Agents: Assess the Most Pressing Need

Anne L. Peters, MD

Disclosures

September 24, 2019

This transcript has been edited for clarity.

Hi. I'm at the European Association for the Study of Diabetes meeting in Barcelona, and I'm going to talk about the use of diabetes medications to reduce the risk for cardiovascular disease (CVD), heart failure, and chronic kidney disease (CKD) in patients with diabetes.

A New Way of Thinking

There has been a huge paradigm shift now that we have medications that reduce glucose levels and the risks for other diabetes complications. The European Society of Cardiology came out with guidelines[1] suggesting that in patients with known heart failure, CVD, or CKD, instead of using metformin as a first-line agent, we immediately jump to the use of an SGLT2 inhibitor or a GLP-1 receptor agonist.

Even though that seems quite shocking to me, since I'm very used to using metformin, we need to consider why we use different agents and in whom we should use them. Metformin is a great drug. It costs pennies a pill, it has a long track record, we know what's good and bad about it, and it lowers glucose levels. We also know that in almost all of the cardiovascular outcomes trials, many of the patients coming into the trials were already on metformin. So the data that we have are from looking at what happens to these high-risk patients when we add on another agent, such as an SGLT2 inhibitor or a GLP-1 receptor agonist.

But what if we have a patient in front of us who is either at high risk for CVD or has known CVD or CKD? What are our goals? Obviously, we want to lower their glucose levels, but the second goal, which is equally important, is to get those patients on an appropriate SGLT2 inhibitor or GLP-1 receptor agonist right away. In my mind, I'm not thinking that metformin is going to fix things until I put the patient on another agent, but rather that I need to start two agents at once or perhaps not start metformin at all. And that's a totally new way of thinking for me and for many of you. We need to consider each patient and what we want to do with them. As an endocrinologist, I also need to consider how my cardiology colleagues are going to view this issue.

Initiating SGLT2 Inhibitors and GLP-1 Receptor Agonists

For those of you who aren't used to starting these newer agents, I want to tell you that there is a nuance to starting them. Let's say you have a patient with an A1c of 6.8%; they have new-onset diabetes but known CKD, and you really want to put them on an SGLT2 inhibitor. First, you need to tell the patient about all the benefits of the SGLT2 inhibitor in terms of renal function. They'll like the fact that it's a pill instead of an injection, and that they're likely to lose some weight. Their A1c will likely improve as well. Second, you need to discuss the adverse effects.

I have found that using an SGLT2 inhibitor can be something of an art form. You need to tell the patient that it's a diuretic for glucose. Many patients have been on hydrochlorothiazide or another diuretic in the past and may have some frame of reference for this. I tell patients that they're going to urinate out glucose and that it is a good thing. It may make them urinate more often. Some patients already urinate often because their diabetes is out of control, but a more well-controlled patient may actually urinate only one or two more times than usual during the day. If they start to urinate even more often than that—I've had patients who urinate every hour—then I want to know about it because that's clearly too much. In some cases, if a patient is really having symptoms on the initial starting dose of one of these agents, I have them cut the pill in half and reduce the dose until they get used to it.

For women, the risk for mycotic vaginal infections increases. Many women with diabetes have had this before, but I warn them and make sure that they're prepared to treat it early if it happens. Men can also get mycotic infections, and I make sure they know about the risk for balanitis. There have been cases of Fournier's gangrene, so I want to be sure that patients tell me right away if they're having any issues.

I'm not so sure that the data suggest a higher risk for urinary tract infections with the SGLT2 drugs, but I mention it as a possibility. I also describe other signs and symptoms of volume depletion; particularly if it's summer and patients are hot, they need to make sure they keep up their fluid intake. So I go through what patients should expect as I start them on the drug.

With GLP-1 receptor agonists, the most common adverse effects I see are gastrointestinal. I warn patients of the risk for diarrhea, constipation, nausea, and vomiting. I always start at a low dose and go up slowly, working with patients through the gastrointestinal symptoms. Most GLP-1 receptor agonists are injections, but I can easily teach a patient how to self-inject. Most of my patients inject themselves once a week without a problem. I believe that oral semaglutide will soon be on the market, so that may well remove another barrier in terms of patients using these agents.

To summarize, make sure you look at your patient and assess their most pressing needs. In patients with known CVD, heart failure, and CKD, the most pressing need is to start an agent that will lower that risk. In addition to statins, blood pressure–lowering agents, and everything else we use, think of GLP-1 receptor agonists and SGLT2 inhibitors. And, of course, there's always metformin, which helps with glucose lowering and may, to some degree, provide cardiovascular benefits. Thank you.

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