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DPP-4 drugs for diabetes may protect kidneys too



– Dipeptidyl peptidase–4 (DPP-4) inhibitors appear to delay the progression of chronic kidney disease (CKD) in patients with type 2 diabetes mellitus (T2DM), a new study has found. Researchers also found that all-cause long-term mortality dropped by an astonishing 78% in patients who took the drugs for an average of more than 3 years.

While the reasons for the impressive mortality results are a mystery, “these medications could have a beneficial effect on the kidneys, and it begins to show after 3 years,” said lead author Mariana Garcia-Touza, MD, of the Kansas City (Missouri) Department of Veterans Affairs Medical Center, in an interview. She presented the results at the meeting, sponsored by the American Society of Nephrology.

DPP-4 inhibitor drugs have been available for more than a decade in the United States. The medications, which include sitagliptin (Januvia) and linagliptin (Tradjenta), are used to treat patients with T2DM who are inadequately controlled by first-line treatments.

The drugs have critics. As UpToDate notes, they’re expensive and their effect on glucose levels is “modest.” In addition, UpToDate says, “some of the DPP-4 inhibitors have been associated with an increased risk of heart failure resulting in hospitalization.”

The authors of the new study sought to understand whether the drugs affect kidney function. As Dr. Garcia-Touza noted, metformin, which is processed in part by the kidneys, is considered harmful to certain patients with kidney disease. However, DPP-4 inhibitors are cleared through the liver. In fact, research has suggested the drugs may actually benefit the liver (Med Sci Monit. 2014 Sep 17;20:1662-7).

For the new study, researchers retrospectively analyzed 20,424 patients with T2DM in the VA system who took DPP-4 inhibitors (average age, 68 years) and compared them with a matched group of 52,118 patients with T2DM who didn’t take the drugs, tracking all patients for a mean of over 3 years.

T2DM control improved slightly in the DPP-4 group but remained worse than the non–DPP-4 group. However, “a significant reduction in progression of CKD was seen” in the DPP-4 group, she said.

The number of patients with creatinine levels above 1.5 mg/dL, 3 mg/dL, and 6 mg/dL was reduced by 7%, 41%, and 47%, respectively, in the DPP-4 group, compared with the other group (P less than .01). And the time to end-stage renal disease (creatinine above 6 mg/dL) was delayed by 144 days in the DPP-4 group (P less than .01).

All-cause mortality also fell by 78% in the DPP-4 group (P less than .0001). “Despite having worse glucose control [than the non–DPP-4 group], these patients have better overall mortality,” Dr. Garcia-Touza said.

The drugs may reduce the burden on the kidneys by decreasing inflammation, she said.

Could DPP-4 drugs be beneficial to patients with CKD even if they don’t have T2DM? Dr. Garcia-Touza wasn’t sure. However, she had a theory about why these kidney benefits didn’t show up in previous research. “My impression is that they didn’t go far enough [in time]. That was the main difference.”

Going forward, Dr. Garcia-Touza said her team plans to study the effects of the drugs on retinopathy and diabetic neuropathy.

The study was funded by the Midwest Biomedical Research Foundation and the VA. The study authors reported no relevant disclosures.

SOURCE: Garcia-Tourza M et al. Kidney Week 2018, Abstract TH-OR035.

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