The effects of dual-therapy intensification with insulin or dipeptidylpeptidase-4 inhibitor on cardiovascular events and all-cause mortality in patients with type 2 diabetes: A retrospective cohort study

Mar 24, 2017Diabetes & vascular disease research

How Adding Insulin or a DPP-4 Inhibitor Affects Heart Risks and Death in People with Type 2 Diabetes

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Abstract

Addition of insulin to dual therapy is associated with 44.5 events per 1000 person-years of cardiovascular complications compared to 14.6 for a dipeptidylpeptidase-4 inhibitor.

A total of 123 composite outcome events occurred in the insulin group, while 171 occurred in the dipeptidylpeptidase-4 inhibitor group.
The adjusted hazard ratio for the composite outcome was 2.6 for insulin compared to the dipeptidylpeptidase-4 inhibitor, indicating a significantly higher risk.
In obese patients, the adjusted hazard ratio for insulin was 3.6, suggesting an even greater risk of complications.
Findings indicate that adding insulin to existing diabetes treatment may increase the risk of cardiovascular events and death.

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PURPOSE: To compare time to a composite endpoint of non-fatal acute myocardial infarction, non-fatal stroke or all-cause mortality in patients with type 2 diabetes mellitus who had their treatment intensified with a dipeptidylpeptidase-4 inhibitor or insulin following dual-therapy (metformin plus sulfonylurea) failure.

METHODS: A retrospective cohort study was conducted on 5238 patients newly treated with either a dipeptidylpeptidase-4 inhibitor or insulin following dual-therapy failure (2007-2014). Data were sourced from UK General Practices. The risk of the composite outcome was compared between two treatment groups: metformin + sulfonylurea + insulin ( n = 1584) and metformin + sulfonylurea + dipeptidylpeptidase-4 inhibitor ( n = 3654), while adjusting for baseline covariates. Follow-up was for up to 5 years. Propensity score matching analysis and Cox proportional hazard models were employed.

RESULTS: Overall, 123 and 171 composite outcome events occurred among patients who added insulin versus dipeptidylpeptidase-4 inhibitor, respectively (44.5 vs 14.6 events per 1000 person-years). Addition of insulin was associated with a significantly higher hazard ratio versus the addition of a dipeptidylpeptidase-4 inhibitor (adjusted hazard ratio = 2.6, 95% confidence interval: 1.9-3.4; p < 0.01), an effect that was more pronounced in obese (body mass index: 30-34.9 kg/m) patients (corresponding adjusted hazard ratio 3.6, 95% confidence interval: 2.3-5.6; p < 0.01). 2

CONCLUSION: In routine clinical practice, intensification of metformin + sulfonylurea therapy by adding insulin is associated with increased risk of cardiovascular events and death compared with adding a dipeptidylpeptidase-4 inhibitor. These findings are in line with suggestions from previous studies regarding the cardiovascular safety of insulin in type 2 diabetes mellitus, but should be interpreted with caution.

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The effects of dual-therapy intensification with insulin or dipeptidylpeptidase-4 inhibitor on cardiovascular events and all-cause mortality in patients with type 2 diabetes: A retrospective cohort study

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