NEW YORK (Reuters Health) – Once-weekly dulaglutide is effective for glycemic control in patients with type 2 diabetes and moderate to severe kidney disease, while helping to slow renal function decline, new research shows.
“This is a major breakthrough in the treatment of people with diabetic kidney disease,” Dr. Katherine R. Tuttle of Providence Health Care, University of Washington, in Spokane, told Reuters Health by phone. “This is huge if we can find a treatment that will preserve kidney function in a clinically meaningful way.”
About 40% of people with type 2 diabetes overall have diabetic kidney disease. This limits the effectiveness of insulin and other antihyperglycemic therapies that are cleared through the kidneys, Dr. Tuttle and her team note in The Lancet Diabetes & Endocrinology, online June 14.
Dulaglutide, a long-acting glucagon-like peptide-1 (GLP-1) receptor agonist made by Eli Lilly and Company, has been approved for treating type 2 diabetes since 2014. The new study, funded by Lilly, is the first to evaluate a GLP-1 receptor agonist in diabetic patients with kidney disease.
Dr. Tuttle, a consultant for Lilly, and her team randomly assigned 577 adults with type 2 diabetes and stage 3 or 4 kidney disease and hemoglobin (Hb) A1c levels of 7.5%-10.5% to basal therapy with once-weekly injectable dulaglutide 1.5 mg, once-weekly dulaglutide 0.75 mg, or daily insulin glargine for 52 weeks.
Change in HbA1c, the study‘s primary outcome, was similar for the three groups at 26 weeks, and dulaglutide continued to be efficacious at 52 weeks.
Patients on dulaglutide lost weight during treatment, while those on insulin gained weight. There were no more than 4.4 hypoglycemic events per patient per year with either dose of dulaglutide, compared to 9.6 episodes in patients on insulin glargine.
Patients on dulaglutide also had a slower decline in estimated glomerular filtration rate (eGFR), and a greater reduction in albuminuria.
“Although the absolute magnitude of eGFR preservation – approximately 1-2 ml/min per 1.73 m2 – might seem small, when amortised over many years, this effect is likely to be of substantial clinical importance, especially in patients with albuminuria,” Dr. David Z. I. Cherney of the University of Toronto and colleagues note in an editorial accompanying the study.
While the mechanism behind GLP-1 receptor agonists’ protective effects are not clear, they add, “non-haemodynamic, antinflammatory pathways probably have an important role, independent of glycemic control.”
“Larger-scale, adequately powered trials are still required to assess the effect of GLP-1 receptor agonists on cardiovascular risk in patients with chronic kidney disease stage 4 and on renal endpoints, such as doubling of serum creatinine, renal replacement therapy, and renal death,” the editorialists add. “Mechanistic studies assessing blood pressure-independent and glucose-independent protective effects with GLP-1 receptor agonists are also needed to provide insight into mechanisms of progressive renal insufficiency in the setting of diabetes and, potentially, in non-diabetic chronic kidney disease.”
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Lancet Diabetes Endocrinol 2018.