Liraglutide better at preventing heart outcomes vs. three other glucose-lowering therapies
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Key takeaways:
- In patients with type 2 diabetes but usually not heart disease, liraglutide had better CV outcomes vs. some other therapies.
- Drugs linked to CV benefit may be appropriate for lower-risk patients with diabetes.
PHILADELPHIA — In the cardiovascular outcomes analysis of the GRADE trial, liraglutide was linked to lower risk for certain CV outcomes compared with other glucose-lowering therapies, researchers reported.
Jennifer B. Green, MD, professor of medicine at Duke University School of Medicine and member in the Duke Clinical Research Institute, presented the results, which were previously published in Circulation, at the Heart in Diabetes CME Conference.
GRADE compared the GLP-1 receptor agonist liraglutide (Victoza, Novo Nordisk), the DPP-IV inhibitor sitagliptin (Januvia, Merck), the third-generation sulfonylurea glimepiride and insulin glargine (Lantus, Sanofi) in adults with type 2 diabetes. As Healio previously reported, in the main results, all four were safe and lowered HbA1c, but primary metabolic outcome of an HbA1c of less than 7% occurred more often in those randomly assigned liraglutide or insulin glargine than in those assigned glimepiride or sitagliptin.
The CV outcomes analysis included 4,730 patients from GRADE (mean age, 57 years; 36% women; 66% white) who completed a mean of 5 years of follow-up. Most patients were on BP and/or lipid-lowering medications, but only 6.5% had a history of heart attack or cerebrovascular accident at baseline. The patients were younger and healthier and had diabetes for a shorter period compared with the cohorts from the CV outcomes trials of the individual diabetes drugs, Green said during a presentation.
Indicators of high risk
The trial “does provide us with an opportunity to assess in a fairly rigorous fashion individual antihyperglycemic agents in lower-risk patients with type 2 diabetes,” she said. “We have this bucket of people who don’t have known established ASCVD, but they have indicators of high risk. It’s not entirely clear ... when ASCVD risk becomes truly high in these individuals. So it’s a little bit difficult to know which patients without ASCVD should be using these agents with outcomes benefits. The GRADE trial ... does permit us to compare cardiovascular outcomes by second-line antihyperglycemic therapy in a large cohort of patients with type 2 diabetes who for the most part did not have established cardiovascular disease.”
The outcomes of interest were MACE-3, defined as CV death, MI and stroke; MACE-4, defined as MACE-3 plus unstable angina requiring hospitalization or revascularization; MACE-5, defined as MACE-4 plus revascularization; MACE-6, defined as MACE-5 plus HF hospitalization; and the individual components.
When the four groups were compared individually, there were no differences in any combined or individual outcomes. However, when Green and colleagues compared the patients assigned liraglutide with those assigned any of the other three therapies, the liraglutide group had lower risk for MACE-5 (adjusted HR = 0.7; 95% CI, 0.54-0.91; P = .021), MACE-6 (aHR = 0.7; 95% CI, 0.55-0.9; P = .021) and HF hospitalization (aHR = 0.49; 95% CI, 0.28-0.86; P = .022).
When the researchers calculated rate ratios comparing each of the other therapies with liraglutide for MACE-6, all three were elevated, though the insulin glargine comparison was no longer significant after adjustment for multiple comparisons, Green said.
Consider lifetime CV risk
“The GRADE outcomes suggest that using liraglutide may also reduce the risk of CV events, even in a relatively low-risk group of patients with type 2 diabetes compared to treatment with the other commonly used glucose-lowering medications which were studied in the trial,” Green said during the presentation. “We would posit that given the substantial lifetime CV risk associated with type 2 diabetes, the current dichotomy in the care of high vs. lower cardiovascular risk in patients with type 2 diabetes may not be justifiable.”
Reference:
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Green JB. Session 14 – Diabetes and CVD. Presented at: Heart in Diabetes CME Conference; June 7-9, 2024; Philadelphia.
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