No improved kidney and CV outcomes with DPP-4 inhibitor in diabetes patients
The dipeptidylpeptidase-4 (DPP-4) inhibitor linagliptin did not have an effect on eGFR and CV events in diabetes patients in the CARMELINA trial, regardless whether they had nephrotic-range proteinuria or not. Linagliptin did lower albuminuria and HbA1c in all patients. These results were presented at the ERA-EDTA (European Renal Association – European Dialysis and Transplant Association) congress in Budapest, Hungary.
In the randomized, double-blind, multicenter CARMELINA trial, the CV effect of linagliptin was compared to placebo, in addition to standard care, in patients with type 2 diabetes and high risk of CV events and/or CKD. In the analysis presented at ERA-EDTA, the cardio-renal burden and effect of linagliptin on CV, eGFR and albuminuria outcomes was examined in diabetes patients with and without nephrotic-range proteinuria (defined as UACR ≥2200 mg/g at baseline).
Nearly 10% of patients in this trial had nephrotic-range proteinuria at baseline (646 of 6979 patients), which is associated with high risk of CV events and poor kidney outcomes; a 3-fold greater decline in eGFR was observed in those with nephrotic-range proteinuria compared to those without. The difference in HbA1c after the duration of the trial (2.2 years) was greater in patients who received linagliptin, independent of nephrotic-range proteinuria status. A larger proportion of patients in the linagliptin group regressed to normoalbuminuria or had a reduction of urine albumin-to-creatinine ratio of ≥50% from baseline, with no difference between patients who had nephrotic-range proteinuria vs. those without. Decline in eGFR was not different between those who received linagliptin vs placebo (-6.51/year vs placebo -7.07/year), nor were 3-point major adverse cardiovascular events (MACE) (HR 1.02, 95%CI: 0.89-1.17), CV mortality (HR 0.96, 95%CI: 0.81-1.14), and all-cause hospitalization (HR: 0.93, 95%CI: 0.85-1.00]), regardless of nephrotic-range proteinuria status.
“The study clearly showed that there is a group of patients with diabetes who clearly are in need of outcome-enhancing therapies, because their prognosis is rather poor. Nephrotic-range proteinuria might be a good marker to stratify these patients. I would advise to treat these patients with SGLT2 inhibitors instead, or a combination of SGLT2 inhibitor and DPP-4 inhibitor. Apart from diabetes control, SGLT2 inhibitors have shown to be effective in renal and cardiovascular risk reduction”, concluded lead investigator Professor Wanner.
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