Liraglutide reduced major heart events in adults with type 2 diabetes

The LEADER trial found that liraglutide (Victoza) lowered the risk of major heart problems in adults with type 2 diabetes who already had cardiovascular disease or were at high risk, according to results published in the New England Journal of Medicine ^[1].

Liraglutide is a glucagon-like peptide-1 (GLP-1) receptor agonist, a class of injected medicines ^[1][2]. When the study was designed, whether adding the drug to standard care changed cardiovascular outcomes was unknown ^[1].

The trial enrolled 9,340 patients and randomly assigned them to liraglutide or a placebo under double-blind conditions, so neither the participants nor their doctors knew which treatment was being given ^[1]. Follow-up lasted a median of 3.8 years ^[1].

The primary composite outcome was the first occurrence of death from cardiovascular causes, nonfatal myocardial infarction (heart attack) or nonfatal stroke. It occurred in 608 of 4,668 patients on liraglutide (13.0%) and in 694 of 4,672 on placebo (14.9%) ^[1]. The hazard ratio was 0.87 (95% CI, 0.78 to 0.97; P<0.001 for noninferiority; P=0.01 for superiority) ^[1].

Cardiovascular deaths accounted for much of the difference: 219 patients (4.7%) in the liraglutide group versus 278 (6.0%) in the placebo group, a hazard ratio of 0.78 (95% CI, 0.66 to 0.93; P=0.007), which works out to a 22% relative reduction ^[1]. Death from any cause was also lower, 381 (8.2%) versus 447 (9.6%), hazard ratio 0.85 (95% CI, 0.74 to 0.97; P=0.02) ^[1].

Nonfatal heart attack, nonfatal stroke and hospitalization for heart failure each happened less often among patients taking liraglutide, but none of those differences was statistically significant, and the trial made no adjustment for multiple comparisons on those exploratory outcomes ^[1].

Gastrointestinal problems were the adverse events most likely to lead patients to stop liraglutide ^[1]. Pancreatitis occurred less often in the liraglutide group, a difference that was not statistically significant ^[1].

Novo Nordisk, which markets Victoza, and the National Institutes of Health funded the study, registered as NCT01179048 ^[1].

Why it matters for patients

The cardiovascular use now on the Victoza label — reducing the risk of major adverse cardiovascular events in adults with type 2 diabetes and established cardiovascular disease — rests on this kind of outcome data ^[2]. That indication was added to the label in May 2025 ^[2].

The benefit was measured in a specific group: people with type 2 diabetes and high cardiovascular risk ^[1]. Whether liraglutide protects the heart in people who have diabetes but no established cardiovascular disease has not been established by this trial. The study also does not answer whether other GLP-1 medicines produce the same result.

Victoza carries a boxed warning that liraglutide causes thyroid C-cell tumors in rats and mice, and that it is unknown whether the drug causes thyroid C-cell tumors, including medullary thyroid carcinoma, in humans ^[2]. The drug is contraindicated in people with a personal or family history of medullary thyroid carcinoma or with Multiple Endocrine Neoplasia syndrome type 2 ^[2].

The most common adverse reactions, each reported in at least 5% of patients in clinical trials, are nausea, diarrhea, vomiting, decreased appetite, dyspepsia and constipation ^[2]. The label also describes a higher risk of low blood sugar, including severe low blood sugar, in adults who also take insulin or an insulin secretagogue; acute kidney injury from volume depletion; severe gastrointestinal reactions; and delayed stomach emptying that can affect how oral medicines are absorbed ^[2]. Victoza is not recommended for people with severe gastroparesis ^[2].

What happens next

Follow-up in the trial ran a median of 3.8 years, so effects of longer treatment have not been reported from this study ^[1]. Victoza's prescribing information was most recently revised in October 2025, with the section on severe gastrointestinal adverse reactions updated that month ^[2]. The drug's initial US approval came in 2010 ^[2].