Risk of cardiovascular disease: The effects of diabetes and anti-diabetic drugs — A nested case–control study

• Biguanides reduce the risk of ischemic heart disease, heart failure and stroke.
• Liraglutide reduces the risk of ischemic heart disease, heart failure and stroke.
• The effects were not tied to patient biochemical values (e.g. lipids and HbA1c).
• This may represent pleiotropic effects beyond glucose-lowering.
• The beneficial effects for liraglutide are dose- and duration-dependent.

AimsType 2 diabetes (DM) increases the risk of cardiovascular disease. We investigated the effects of antidiabetic drugs on the composite endpoint (CE) of ischemic heart disease, heart failure or stroke in DM patients.MethodsWe conducted a nested case–control study. Cases were DM patients who subsequently suffered from CE; controls were DM patients with no history of CE after DM diagnosis. Using the Danish National Hospital Discharge Register, we included DM patients with information on date of DM diagnosis, date of CE, and comorbidities. From the Central Region of Jutland, Denmark, medication use and biochemical parameters were collected. Logistic regression analyses were conducted and mutually adjusted for comorbidities, pharmaceutical use, and biochemical parameters.Results10,073 DM patients were included (65,550 person-years). 1947 suffered from a subsequent CE. CE prior to DM diagnosis (OR = 20.18, 95% CI: 16.88–24.12), neuropathy (OR = 1.39, 95% CI: 1.05–1.85) and peripheral artery disease (OR = 1.31, 95% CI: 1.02–1.69) increased the risk of CE. Biguanides (OR = 0.62 95% CI; 0.54–0.71) and liraglutide (OR = 0.48 95% CI; 0.38–0.62) significantly decreased the risk of CE as did statin treatment (OR = 0.63, 95% CI: 0.54–0.72). DPP-4 inhibitors, insulin and β-cell stimulating agents had neutral effect. When results were adjusted for biochemical risk markers (1103 patients, 7271 person-years, 189 cases), biguanides (OR = 0.54, 95% CI: 0.34–0.87) and liraglutide (OR = 0.32, 95% CI: 0.14–0.70) treatment retained a significant risk reduction. The effect of liraglutide was dose and duration dependent (p < 0.05).ConclusionWe have shown an association between the use of biguanides and liraglutide and a reduced risk of CE in DM patients.