Long-Acting Insulin Analogues Reduce MACE Risk in Patients with T2D

Kristian B. Filion, PhD

Patients with type 2 diabetes (T2D) may see a modestly reduced risk of major adverse cardiovascular events (MACE) with the use of long-acting insulin analogues, compared to the use of neutral protamine Hagedorn (NPH) insulin.

In new findings, insulin glargine and detemir had modest associations with a reduced risk of MACE compared to NPH insulin, but results for insulin degludec were determined inconclusive due to wide confidence intervals (CI).

“Long-acting insulins were associated with a reduced risk of hospitalization for heart failure, myocardial infarction, cardiovascular death and all-cause mortality but were not associated with the risk of ischemic stroke,” wrote study author Kristian B. Filion, PhD, Departments of Medicine and of Epidemiology, Biostatistics, and Occupational Health, McGill University.

Citing uncertainty on the real-word cardiovascular effects of basal insulins, Fillion and colleagues’ objective was to compare the effectiveness of long-acting insulin analogues and NPH insulin at reducing MACE risk in the patient population with T2D.

They collected data from the UK Clinical Practice Research Datalink Aurum linked with hospitalization and vital statistics data and included relevant patients between September 2002 - November 2018. Using a time-varying approach, investigators defined exposure as the current use of long-acting analogues of NPH insulin.

The cohort included 57,334 patients. Of this population, 31,136 were users of long-acting insulin analogues and 26,198 were users of NPH insulin at baseline.

Data show a total of 3494 MACE occurred over a mean follow-up of 1.6 years (incidence rate, 37.4; 95% CI, 36.2 to 38.7 per 1000 person-years).

The findings suggest long-acting insulin analogues were associated with reduced risk of MACE compared to NPH after weighting and adjustments for baseline confounders (hazard ratio, 0.89; 95% CI, 0.83 - 0.96).

Molecule-specific analyses show glargine was associated with a reduced risk of MACE as compared to NPH (HR, 0.88; 95% CI, 0.81 - 0.95). The adjusted HR for MACE was 0.91 (95% CI, 0.81 - 1.02) for detemir and 0.91 (95% CI, 0.47 to 1.76) for degludec.

Compared with the use of NPH, the use of long-acting insulin analogues was associated with reduced risk of:

• hospitalization for heart failure (HR, 0.82; 95% CI, 0.77 to 0.88)
• myocardial infarction (HR, 0.85; 95% CI, 0.74 - 0.99)
• cardiovascular death (HR, 0.90; 95% CI, 0.82 - 0.99)
• all-cause mortality (HR, 0.88; 95% CI, 0.82 - 0.94)

However, it was not associated with the risk of ischemic stroke (HR 0.95; 95% CI 0.81 - 1.13).

Subgroup analyses reveal long-acting insulin analogues were associated with a reduced risk of MACE in patients aged <70 years and in patients with a history of cardiovascular disease (CVD).

“It is possible that long-acting insulin analogues provide greater cardiovascular benefits among patients with an increased risk of MACE at baseline, as history of CVD is an important risk factor for future cardiovascular events,” Filion added.

The study, “The association of long-acting insulin analogue use versus neutral protamine Hagedorn insulin use and the risk of major adverse cardiovascular events among individuals with type 2 diabetes: A population-based cohort study,” was published in Diabetes, Obesity, And Metabolism.