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Effects of long-acting insulin analogues versus NPH on cardiovascular events in people with type 2 diabetes

Modest but significant reductions in the risk of cardiovascular events with long-acting analogues compared to NPH insulin.

Randomised controlled trials have demonstrated similar efficacy between long-acting insulin analogues (including glargine, detemir and degludec) and intermediate-acting NPH insulin in terms of glycaemic control, while meta-analyses have suggested reduced risk of hypoglycaemia with the former. The present retrospective cohort study sought to compare the effects of the two insulin types on cardiovascular outcomes.

Using data from the UK Clinical Practice Research Datalink, 57,344 people with type 2 diabetes who initiated basal insulin therapy with either long-acting or NPH insulin between September 2002 and November 2018 were evaluated. The primary outcome was time to 3-point major adverse cardiovascular events (MACE).

Over a mean follow-up of 1.6 years, the incidence of MACE was 37.4 per 1000 person-years. After weighting and adjustment for baseline confounders, the risk of MACE was reduced with long-acting insulin analogues compared with NPH (hazard ratio [HR], 0.89; 95% CI, 0.83–0.96). The risks of hospitalisation for heart failure, cardiovascular death and all-cause death were significantly reduced; however, reductions in ischaemic stroke were not significant.

Long-acting analogues were associated with reduced risk of MACE in people aged <70 years (HR, 0.85) but not over 70 years, and in those with a history of cardiovascular disease (HR, 0.91) but not those without prior history. Reduced risk was also observed in those who were using other diabetes drugs at baseline (HR, 0.86) but not in those who were not on other diabetes drugs.

It is hypothesised that these results may be due to the reduced peaks of action and longer time–action profiles of long-acting analogues, which may help to avoid both hyper- and hypoglycaemia, both of which are associated with cardiovascular events.

The authors conclude that long-acting insulin analogues are associated with modest reductions in the risk of cardiovascular events compared with NPH insulin in people with type 2 diabetes.

Click here to read the study in full.


Brunetti VC, Yu OHY, Platt RW, Filion KB (2022) 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. Diabetes Obes Metab 21 Jun [Epub ahead of print]. doi: 10.1111/dom.14802

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