For many type 2 diabetes patients, failure to maintain glucose control with dual therapy (metformin + sulphonylurea at maximum doses) requires further treatment intensification with a third-line anti-diabetic agent. However, while a variety of treatment options exist, there is limited data on long-term cardiovascular safety for these agents.

In this retrospective cohort study published online in the journal Heart, researchers sought to compare the effects of treatment intensification with either a GLP-1 receptor agonist or insulin in patients with type 2 diabetes following failure of dual therapy with metformin and sulphonylurea. Over 2,000 patients were included in the study which included 5 years of follow-up (6614 person-years). The primary objective of the study was to assess the risks of MACE (non-fatal myocardial infarction, non-fatal stroke and all-cause mortality) between those taking a combination of metformin + sulphonylurea + GLP-1 receptor agonist (n= 419) versus those taking metformin + sulphonlyurea + insulin (n=1584). 

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Overall, there were 231 major cardiovascular events in the insulin group versus 11 in the GLP-1 receptor agonist group  (44.5 vs 7.7 per 1000-person-years adjusted HR: 0.27; 95% CI 0.14 to 0.53; P<0.0001).  A significant increase in weight  was seen in the insulin group compared to the GLP-1 receptor agonist group (1.78 vs −3.93kg; P<0.0001), however HbA1c reduction was similar between both groups (−1.29 vs −0.98; P=0.156). In obese patients, there were 84 major cardiovascular events in the insulin group compared to 11 in the GLP-1 receptor agonist group (38.6 vs 8.1 per 1000 person-years; adjusted HR: 0.31; 95% CI 0.16 to 0.61; P=0.001).

Compared with insulin, the use of GLP-1 receptor agonist appears to be linked to reduced cardiovascular events and mortality. The authors note that “in people with type 2 diabetes who require intensification of glucose-lowering therapy following failure of metformin and sulfonylurea, GLP-1 analogues should be considered first before insulin treatment, especially in patients who are overweight.”

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