COMMENTARY

New Drug Classes for Diabetes Mean New Options

Cyrus V. Desouza, MBBS

Disclosures

June 30, 2017

Editorial Collaboration

Medscape &

Hello. I am Cyrus Desouza. I am an endocrinologist from Nebraska. Today we are going to discuss three new classes of drugs, their clinical usefulness, and certain subsets of patients in whom they should be avoided.

Incretin Drugs

GLP-1 Receptor Agonists

The glucagon-like peptide-1 (GLP-1) agonists have been around for a while and a lot of new ones are on the market. They are divided into short-acting and long-acting agents.[1]

Short-acting GLP-1 agonists, such as lixisenatide, have more pronounced effects on postprandial blood sugar.[2] This might be the ideal medication to use in patients with postprandial blood sugar problems.

Longer-acting, once-weekly, or once-daily agents, like liraglutide, would be effective both in the fasting as well as in the postprandial state.[2] For patients who have both problems, this would be a great medication to go with.

Recently, clinical trials have shown other advantages of GLP-1 agonists. Addition of these drugs to basal insulin is very effective for glycemic control. The combination has been shown to cause less hypoglycemia and less weight gain in comparison with other combinations.[3] This is one area where it can be useful.

Some of these drugs have been found to have cardiovascular benefits. For example, in the LEADER study,[4] liraglutide was shown to decrease mortality, and in the SUSTAIN study,[5] semaglutide was shown to reduce mortality. Some of these drugs could be used in patients with high cardiovascular risk, such as those who have had heart attacks, strokes, or previous cardiac events.

DPP-4 Inhibitors

Let's move on to another new class of drugs called dipeptidyl peptidase 4 (DPP-4) inhibitors. They are also part of the incretin system and have a very safe side-effect profile. These drugs are useful because they do not cause that much hypoglycemia and are taken orally.[6] They are very useful for patients who need a modest amount of A1c lowering and in older patients who are afraid of hypoglycemia.

Adverse Effects of Incretin Drugs

The downside of incretin drugs is that gastrointestinal side effects are very common, especially with GLP-1 agonists.[7,8] This can be avoided by a very slow titration of the drug over time. Most patients are able to overcome these symptoms over a short period.

GLP-1 receptor agonists should be avoided in patients who have severe or moderate gastroparesis[8] and in patients who have a family history of medullary thyroid cancer.[7]

Use caution with GLP-1 receptor agonists and DPP-4 inhibitors in patients who have had gallstones or pancreatitis in the past.[7]

SGLT2 Inhibitors

The sodium-glucose cotransporter 2 (SGLT2) inhibitor is a new class of drugs that excretes glucose in the kidneys. They are very useful for lowering blood sugar that is non-insulin-dependent, and for lowering blood pressure. An advantage is that they also decrease weight.[9]

However, they are not very effective in patients with renal impairment (glomerular filtration rate < 45 mL/min).[10] Side effects include fragility fractures in older patients.[11]

Because they act like diuretics, they can cause hypotension in many patients, perhaps due to dehydration.[9] Therefore, they should be used with caution in older patients and in patients with renal problems.

In conclusion, it is challenging to gather information on side effects and benefit profiles on the many medications for diabetes that are coming out so rapidly. It is very important to understand these drug classes in order to prescribe them to the correct patient population.

I hope you have found this session beneficial. Thank you very much for joining me today.

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