PHILADELPHIA — Some of the leading safety trials of newer anti-hyperglycemic drugs in patients with type 2 diabetes have shown reductions in cardiovascular risks, while others have demonstrated no cardiovascular risk, according to a presenter at the Heart in Diabetes Clinical Education Conference.
“Results of the EMPA-REG Outcome and LEADER trials represent a clinical breakthrough representing the first two antidiabetic interventions [empagliflozin (Jardiance, Boehringer Ingelheim), an SGLT2 inhibitor, and liraglutide (Victoza, Novo Nordisk), a GLP1 receptor agonist, respectively] to unequivocally show cardiovascular risk reduction in type 2 diabetes,” Sanjay Kaul, MD, FACC, FAHA, an attending physician at the Smidt Heart Institute at Cedars-Sinai Medical Center in Los Angeles, told attendees.
In addition, the SUSTAIN-6 CV safety trial unexpectedly demonstrated a reduction in major adverse cardiac events with the GLP1 receptor agonist semaglutide (Ozempic, Novo Nordisk), he said, although the study design did not allow an inference of efficacy for CV risk reduction.
However, other trials have left queries unanswered or urge careful watchfulness moving forward, Kaul said.
“Whether the CANVAS program provides the substantial evidence needed to establish that canagliflozin [Invokana, Janssen] reduces cardiovascular risk [in patients with] type 2 diabetes remains an open question,” Kaul said. “In addition, the discordant mortality result in CANVAS and CVD-REAL serves as a cautionary tale for the enthusiastic advocates of real-world evidence derived from registry data to inform regulatory decisions and guide clinical practice,” he said.
According to Kaul, the CV profiles of many drugs for patients with type 2 diabetes are evaluated in these trials, as well as the REVEAL and ODYSSEY trials, and are assessed for their quality and quantity of benefit and the benefit/risk ratios. These evaluations assist the American Diabetes Association in making its recommendations for lowering cardiovascular risk in patients with type 2 diabetes and established cardiovascular disease.
“Only two drugs have the highest level of recommendation [from ADA]: empagliflozin and liraglutide have a level A recommendation for MACE reduction and cardiovascular mortality reduction. Semaglutide and dapagliflozin [Farxiga, AstaZeneca] are not recommended simply because the evidence is not there yet,” he said.
“Canagliflozin is not recommended [by ADA] for cardiovascular mortality reduction, but it does have a level C recommendation, a low quality of evidence recommendation for MACE risk reduction,” Kaul added. – by Janel Miller
Reference: Kaul S. Mitigating CV risk with anti-diabetes and anti-lipids drugs. Presented at: Heart in Diabetes Clinical Education Conference; July 13-15, 2018; Philadelphia.
Disclosures: Kahl reports he is a consultant for Amgen, Boehringer-Ingelheim, Johnson and Johnson, Novo Nordisk, Regeneron and Sanofi.