Canagliflozin, Linagliptin Shown to Benefit CV and Renal Function

Trial results presented at the American Diabetes Association’s (ADA) 79th Scientific Sessions demonstrated the cardiovascular and renal benefits of various newer therapies for patients with type 2 diabetes. Canagliflozin, a sodium-glucose cotransporter 2 inhibitor, and linagliptin, a dipeptidyl peptidase-4 inhibitor, were no exception.

In the CREDENCE trial (N = 4401), treatment with canagliflozin was associated with a 30% lower relative risk of end-stage kidney disease, a doubling of the serum creatinine level, or cardiovascular-related or renal-related death compared with placebo among participants with type 2 diabetes and kidney disease.¹

This, among other key findings, prompted investigators to stop the trial early.

“We are excited for our patients about the magnitude of the improvement in kidney and heart outcomes,” said the study’s co-principal investigator Kenneth Mahaffey, MD, vice chair of clinical research in the department of medicine at Stanford University and the director of the Stanford Center for Clinical Research, in a press release. “The benefits were consistent in many different subgroups of patients, and this is the first treatment advance for patients with type 2 diabetes and chronic kidney disease in nearly [2] decades,” he added.²

Study co-investigator, Meg Jardine, MBBS, PhD, echoed these sentiments. “Patients with type 2 diabetes are already at a high risk for serious kidney or cardiac events. This risk is even higher in those who have chronic kidney disease, and canagliflozin reduces the chance of these events safely and effectively without increasing negative side effects,” said Dr Jardine, who is conjoint associate professor of medicine at the University of New South Wales in Australia, and program head at the George Institute for Global Health, in a press release.²

Findings on linagliptin from the CARMELINA trial, released in January, were also discussed in a symposium at the ADA’s meeting. The trial examined the risk of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke among participants with type 2 diabetes and an increased risk of cardiovascular and/or renal disease who were randomly assigned to treatment with linagliptin (n = 3494) or placebo (n = 3485).³

Overall, treatment with linagliptin in addition to usual care was found to be noninferior to placebo over a median 2.2 years of follow-up.

“This data is particularly important because it proves categorically the cardiovascular and kidney safety of linagliptin in those with type 2 diabetes who are at a high cardiovascular risk when some degree of kidney disease is associated,” said lead investigator Julio Rosenstock, MD, director of the Dallas Diabetes Research Center at Medical City and clinical professor of medicine at the University of Texas Southwestern Medical Center, in a press release.⁴

“These are patients that nearly every provider sees in his or her clinical practice on a daily basis and are difficult to treat because of risk of hypoglycemia, which was not increased with linagliptin, and these patients had better glucose control,” he added.⁴

Linagliptin and canagliflozin were approved by the US Food and Drug Administration in 2011 and 2013, respectively, for the treatment of adults with type 2 diabetes. Both drugs were approved as an adjunct to diet and exercise.

—Christina Vogt

References:

1. Perkovic V, Jardine MJ, Neal B, et al. Canagliflozin and renal outcomes in type 2 diabetes and nephropathy. N Eng J Med. 2019; 380:2295-2306. doi:10.1056/NEJMoa1811744.
2. Canagliflozin shown to improve cardiovascular and renal outcomes in people with type 2 diabetes and kidney disease [press release]. San Francisco, CA. American Diabetes Association. https://www.diabetes.org/newsroom/press-releases/2019/canagliflozin-shown-to.html. June 11, 2019. Accessed June 13, 2019.
3. Rosenstock J, Perkovic V, Johansen OE, et al. Effect of linagliptin vs placebo on major cardiovascular events in adults with type 2 diabetes and high cardiovascular and renal risk: The CARMELINA Randomized Clinical Trial. JAMA. 2019;321(1):69-79. doi:10.1001/jama.2018.18269.
4. Safety of linagliptin for adults with type 2 diabetes who have high risk of cardiovascular and/or renal disease examined in CARMELINA [press release]. San Francisco, CA. American Diabetes Association. https://www.diabetes.org/newsroom/press-releases/2019/safety-of-linagliptin-for.html. June 11, 2019. Accessed June 13, 2019.