For people with both type 2 diabetes and advanced chronic kidney disease (CKD), taking a GLP-1 agonist was linked to a lower risk of death compared with taking a DPP-4 inhibitor, according to a new study published in the journal JAMA Network Open.
Both GLP-1 agonists and DPP-4 inhibitors are categories of drugs developed to help reduce blood glucose levels in people with type 2 diabetes. While these two kinds of drugs work through different mechanisms in the body, the effect of both is to reduce the release of glucagon — a hormone that raises blood glucose — and increase the release of insulin in the body. GLP-1 agonists include Byetta (generic name exenatide), Bydureon BCise (exenatide), Ozempic (semaglutide), Trulicity (dulaglutide), Adlyxin (lixisenatide), and Victoza (liraglutide). DPP-4 inhibitors include Januvia (sitagliptin), Nesina (alogliptin), Onglyza (saxagliptin), and Tradjenta (linagliptin). Previous research has shown that GLP-1 agonists may have benefits other than lowering blood glucose, with one study showing that these drugs may reduce the risk for glaucoma, a serious eye disorder that can lead to blindness. Studies have also shown that given how effective they are at reducing blood glucose, GLP-1 agonists aren’t prescribed very widely for people with type 2 diabetes — especially among certain racial and ethnic minority groups.
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For the latest study, researchers looked at a group of 27,279 people with type 2 diabetes and advanced chronic kidney disease who took either a GLP-1 agonist or a DPP-4 inhibitor. The overwhelming majority of these participants — 26,578 — took a DPP-4 inhibitor, while only 701 took a GLP-1 agonist. All participants lived in Taiwan, and the average age in the GLP-1 group was 59, while the average age in the DPP-4 group was 65. Participants were followed from he beginning of 2012 until the end of 2018.
Lower risk of death from sepsis linked to GLP-1 agonists
After adjusting for differences — such as age — between participants who took the two different types of drugs, the researchers found that participants who took a GLP-1 agonist were 21% less likely to die during the study period, compared with those who took a DPP-4 inhibitor. They were also 39% less likely to die specifically of sepsis — a life-threatening response by the body to an infection — and other infection-related causes of death. When the researchers looked at different subgroups of participants based on health conditions and other characteristics, they found that participants with cerebrovascular disease — those with restricted blood flow or other blood vessel problems affecting the brain — saw a much greater benefit from taking GLP-1 agonists than those who didn’t have cerebrovascular disease. Compared with taking a DPP-4 inhibitor, taking a GLP-1 agonist was linked to 67% lower risk of dying among participants with cerebrovascular disease, but only an 11% lower risk of dying among participants without cerebrovascular disease.
The researchers noted that it was already widely known that people with diabetes and chronic kidney disease are generally more likely to develop sepsis, and to experience worse outcomes if they develop it, compared with people who don’t have diabetes or chronic kidney disease — making the lower risk of death from sepsis among participants who took GLP-1 agonists notable. But the latest study had several limitations, including that it may not have had a long enough follow-up period to compare the risk of dying from certain health conditions. Further large-scale studies are needed, they wrote, to gain a better understanding of the different effects of taking GLP-1 agonists or DPP-4 inhibitors in people with type 2 diabetes and chronic kidney disease.
Want to learn more about keeping your kidneys healthy with diabetes? Read “Managing Diabetic Kidney Disease,” “How to Keep Your Kidneys Healthy,” “Protecting Your Kidneys,” and “Kidney Disease: Your Seven-Step Plan for Prevention.”
