February 04, 2015
2 min read

Safety of Onglyza unaltered by kidney function

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Onglyza treatment did not alter the risk for ischemic cardiovascular events in patients with type 2 diabetes who had a range of impaired renal function, according to research published in Diabetes Care.

“This study demonstrates that the overall efficacy and safety of saxagliptin was similar in patients with chronic kidney disease compared to patients with normal renal function,” Benjamin M. Scirica, MD, MPH, in the cardiovascular division, Brigham and Women’s Hospital and Harvard Medical School, told Endocrine Today.

Benjamin Scirica

Benjamin M. Scirica

Scirica, with Jacob A. Udell, MD, MPH, of the Women’s College Hospital, University of Toronto, and colleagues from other institutions investigated the effect of Onglyza (saxagliptin, AstraZeneca/Bristol-Myers Squibb) according to renal function at baseline in the SAVOR-TIMI 53 trial.

“Saxagliptin neither increased nor decreased the risk of the primary endpoint — cardiovascular death, myocardial infarction or ischemic stroke — in patients with chronic kidney disease,” Scirica said. “Moreover, the benefit in reducing HbA1c and the relative risk of hospitalization for heart failure with saxagliptin was similar, regardless of renal function.”

The investigators stratified patients by renal function: normal or mildly impaired renal function (estimated glomerular filtration rate > 50 mL/min/1.73 m2; n = 13,916); moderate impairment (eGFR 30-50 mL/min/1.73 m2; n = 2,240); or severe impairment (eGFR < 30 mL/min/1.73 m2; n = 336). Patients were randomly assigned saxagliptin or placebo and followed for an average of 2 years.

Compared with placebo, saxagliptin did not increase or decrease risks for primary (CV death, MI or ischemic stroke) and secondary composite endpoints.

The risk of hospitalization for heart failure was 2.2% (referent) in the normal or mildly impaired renal function group, 7.4% in the moderate impairment group (adjusted HR = 2.38; 95% CI, 1.95–2.91) and 13% in the severe impairment group (adjusted HR = 4.59; 95% CI, 3.28-6.28).

With saxagliptin therapy, the RR for heart failure hospitalization was similar in patients with eGFRs > 50 mL/min/1.73 m2 (HR = 1.23; 95% CI, 0.99-1.55), from 30 mL/min/1.73 m2 to 50 mL/min/1.73 m2 (HR = 1.46; 95% CI, 1.07-2) and less than 30 mL/min/1.73 m2 (HR = 0.94; 95% CI, 0.52-1.71).

Patients with impaired renal function demonstrated reductions in microalbuminuria with saxagliptin (P = .041) similar to those of the overall trial population.

“With this trial, we likely have more data on saxagliptin in patients with moderately to severely impaired renal function than any other diabetes medicine,” Scirica said. “Therefore, clinicians should feel more comfortable when considering the option of saxagliptin, specifically in patients with chronic kidney disease classes 1 to 3.”

A few randomized trials have been conducted in patients with severe kidney disease, which Scirica said limits guidance for clinical care — particularly with chronic kidney disease seen frequently with diabetes.

“More and larger studies in patients with concurrent diabetes and chronic kidney disease, for all types of therapy, are needed,” Scirica said. – by Allegra Tiver

For more information:

Benjamin M. Scirica, MD, MPH, can be reached at TIMI Study Group, Cardiovascular Division, Brigham and Women’s Hospital, Harvard Medical School, 350 Longwood Ave., Boston, MA 02115; email: bscirica@partners.org.

Disclosure: Scirica reports research grants through the TIMI Study Group and Brigham

and Women’s Hospital from AstraZeneca and Bristol-Myers Squibb, and through Bayer Healthcare, Daiichi-Sankyo, Eisai, Gilead, GlaxoSmithKline, Johnson & Johnson and Merck; and consulting fees from Arena, Boston Clinical Research Institute, Bristol-Myers Squibb, Decision Resources, Eisai, Elsevier Practice Update Cardiology, Forest Pharmaceuticals, Gilead, Lexicon, St. Jude’s Medical and University of Calgary. Please see the full study for a list of all other authors’ relevant financial disclosures.