番茄社区

SAN FRANCISCO -- The GLP-1 receptor agonist dulaglutide (Trulicity) slowed renal function decline in some patients with type 2 diabetes and poor kidney functioning, researchers said here, and they found a biomarker that predicted which ones.

In a post-hoc analysis of the , treatment with dulaglutide significantly reduced risk of a composite renal outcome in patients with moderate-to-severe chronic kidney disease and macroalbuminuria at baseline when compared with insulin glargine, Katherine Tuttle, MD, of the University of Washington in Seattle, reported at the annual meeting of the American Diabetes Association.

Specifically, in patients with macroalbuminuria at enrollment, only 7.1% of patients on a weekly injection of 1.5 mg of dulaglutide experienced 40% or greater eGFR decline, progression to end-stage renal disease, or kidney disease-related death, compared with 22.2% of patients on insulin glargine. A total of 16.7% of patients on 0.75 mg of dulaglutide experienced the composite outcome.

"The benefits of dulaglutide were driven by results in this group of participants [excreting large amounts of albumin], who's a group at very high risk for CKD progression," Tuttle explained during a press conference on the findings.

She also noted that there was no statistically significant benefit seen in the microalbuminuria or normal albuminuria subgroups, probably due to the very low rate of renal events seen in these groups.

"AWARD-7 is the first study to report a reduced risk of 40% eGFR decline and end-stage renal events by GLP-1 receptor agonists in patients who have established moderate-to-severe chronic kidney disease," she stated.

In July 2019, dulaglutide's label was updated to include , showing the drug was effective in people with type 2 diabetes and moderate-to-severe chronic kidney disease.

The open-label study included 576 adults with HbA1c of 7.5%-10.5% and eGFR from 15 and 60 mL/min/1.73 m². Individuals with stage 5 chronic kidney disease -- defined as eGFR less than 15 mL/min/1.73 m² were excluded from the analysis.

At baseline, eGFR was lowest among those with macroalbuminuria, defined as a urine albumin-to-creatinine ratio (UACR) over 300 mg/g. Microalbuminuria was considered to be UACR of 30-300 mg/g, while normal albuminuria was a UACR under 30 mg/g.

Across all albuminuria subgroups, there were no events of kidney-related deaths.

"The emerging data on renal protection with diabetic agents is exciting. For so long, we had very few interventions to prevent progression of CKD," commented Grenye O'Malley, MD, of the Icahn School of Medicine at Mount Sinai in New York, who was not involved with the study.

"Going forward, parsing out what patient factors can predict response to these agents is going to be important for tailoring our regimens," she told 番茄社区, highlighting the benefit of identifying macroalbuminuria as a predictor, as seen in this data.

However, she added that one limitation to the study was the comparator of insulin glargine. "One question I have is what the overall glycemic control of the two groups looked like. They both used fast acting insulin -- I assume this was to try to maintain similar glycemic control, but a combination of dulaglutide with prandial insulin without basal insulin would not be a real world regimen."

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