Treatment with Liraglutide Reduces the Risk of Heart Attack and Stroke in Patients with Type 2 Diabetes

A long-term outcomes trial found that, compared to placebo, use of the diabetes medication liraglutide (Victoza) is associated with lower rates of nonfatal stroke, nonfatal myocardial infarction, and cardiovascular death.

 

Investigators randomized 9,340 patients between placebo and liraglutide and followed them for an average of 3.8 years. Overall, 608 of 4,668 liraglutide patients (13%) and 694 of 4,672 placebo patients (14.9%) suffered stroke, myocardial infarction or cardiovascular death death during the study period (hazard ratio [HR] for liraglutide users, 0.87; 95% confidence interval [CI], 0.78-0.97; P<0.001 for noninferiority; P=0.01 for superiority).

 

Cardiovascular events killed 219 liraglutide patients (4.7%) and 278 placebo patients (6.0%) (HR, 0.78; 95% CI, 0.66-0.93; P=0.007). Overall, 381 liraglutide patients (8.2%) and 447 placebo patients (9.6%) died during the study period (HR, 0.85; 95% CI, 0.74-0.97; P=0.02). The rates of nonfatal myocardial infarction, nonfatal stroke, and hospitalization for heart failure were also lower in the liraglutide group, but not significantly so.

 

The number of patients who would need to be treated to prevent 1 event (ie, stroke, myocardial infarction or cardiovascular death) in 3 years was 66, and the number of patients who would need to be treated in order to prevent 1 death from any cause in 3 years was 98.

 

The trial was large enough and lasted long enough to prove liraglutide’s cardiovascular benefits with a high degree of certainty, but study authors could only speculate about the cause of those benefits.

 

 

“The pattern of cardiovascular benefits that were associated with liraglutide in our trial appears to differ from that with the sodium–glucose cotransporter 2 (SGLT2) inhibitor empagliflozin in the previously reported EMPA-REG OUTCOME trial. The time to benefit emerged earlier in that trial than in the present trial, and the heterogeneity of the direction and magnitude of the effects on the components of the composite primary outcome in that trial contrasts with the consistency of the effect in the present trial,” the study authors wrote in the New England Journal of Medicine.

 

“Although these differences may reflect patient populations or chance, the observed benefits in that trial may be more closely linked to hemodynamic changes, whereas in the present trial, the observed benefits are perhaps related to the modified progression of atherosclerotic vascular disease.”

 

The cardiovascular trial also tracked glycemic control and microvascular outcomes for both liraglutide and placebo patients. At 36 months, liraglutide patients, on average, had HbA1c levels 0.40 percentage points below those of placebo patients (95% CI, −0.45 to −0.34). The incidence of a composite outcome that noted both renal and retinal microvascular events was also lower in the liraglutide group than in the placebo group (HR, 0.84; 95% CI, 0.73-0.97; P=0.02).

 

“The benefit with liraglutide was driven by lower rates of renal outcomes, such as new-onset persistent macroalbuminuria in particular. There was a higher rate of retinopathy events with liraglutide than with placebo, although the difference was not significant,” the study authors wrote. “With moderate differences in glycemic control between the trial groups over a median 3.8 years of follow-up, the achievement of renal microvascular benefits is surprising. It is uncertain whether this finding relates to the direct effects of liraglutide on kidney function.”