Cardiovascular events and all-cause mortality with insulin versus glucagon-like peptide-1 analogue in type 2 diabetes

May 25, 2016Heart (British Cardiac Society)

Heart problems and overall death risk with insulin compared to GLP-1 drugs in type 2 diabetes

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Abstract

A total of 231 major adverse cardiovascular events occurred in patients who added insulin compared to 11 in those who added a GLP-1 analogue.

Patients who added insulin experienced 44.5 major adverse cardiovascular events per 1000-person-years compared to 7.7 for those who added a GLP-1 analogue.
The adjusted hazard ratio for major adverse cardiovascular events was 0.27, indicating a significantly lower risk with GLP-1 analogue treatment.
Insulin treatment was associated with an increase in body weight (1.78 kg) while GLP-1 analogue treatment resulted in a weight loss (-3.93 kg).
Both treatment groups achieved similar reductions in hemoglobin A1c levels, with a change of -1.29 for insulin and -0.98 for GLP-1 analogue.
In obese patients, adding insulin was linked to 84 major adverse cardiovascular events compared to 11 for those on GLP-1 analogue, with an adjusted hazard ratio of 0.31.

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OBJECTIVES: To analyse time to cardiovascular events and mortality in patients with type 2 diabetes (T2D) who received treatment intensification with insulin or a glucagon-like peptide-1 (GLP-1ar) analogue following dual therapy failure with metformin (MET) and sulphonylurea (SU).

METHODS: A retrospective cohort study was conducted in 2003 patients who were newly treated with a GLP-1ar or insulin following dual therapy (MET+SU) failure between 2006 and 2014. Data were sourced from The Health Improvement Network database. Risks of major adverse cardiovascular events (MACE) (non-fatal myocardial infarction, non-fatal stroke and all-cause mortality) were compared between MET+SU+insulin (N=1584) versus MET+SU+GLP-1ar (N=419). Follow-up was for 5 years (6614 person-years). Propensity score matching analysis and Cox proportional hazard models were employed.

RESULTS: Mean age was 52.8±14.1 years. Overall, the number of MACE was 231 vs 11 for patients who added insulin versus GLP-1ar, respectively (44.5 vs 7.7 per 1000-person-years adjusted HR (aHR): 0.27; 95% CI 0.14 to 0.53; p<0.0001). Insulin was associated with significant increase in weight compared with GLP-1ar (1.78 vs -3.93 kg; p<0.0001) but haemoglobin A1c reduction was similar between both treatment groups (-1.29 vs -0.98; p=0.156). In a subgroup analysis of obese patients (body mass index >30 kg/m(2)) there were 84 vs 11 composite outcomes (38.6 vs 8.1 per 1000 person-years; aHR: 0.31; 95% CI 0.16 to 0.61; p=0.001) in the insulin and GLP-1ar groups, respectively.

CONCLUSIONS: In this cohort of obese people with T2DM, intensification of dual oral therapy by adding GLP-1ar analogue is associated with a lower MACE outcome in routine clinical practice, compared with adding insulin therapy as the third glucose-lowering agent.

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Cardiovascular events and all-cause mortality with insulin versus glucagon-like peptide-1 analogue in type 2 diabetes

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