(HealthDay News) — For patients with type 2 diabetes who are taking metformin, the risk of cardiovascular events and mortality varies with the addition of different second-line therapies, according to a study published online in Diabetes, Obesity and Metabolism.

Nils Ekström, MD, PhD, from the University of Gothenburg in Sweden, and colleagues examined the relative safety of glucose-lowering agents as add-on medication to metformin in type 2 diabetes. Patients on metformin therapy who started another agent were eligible for inclusion; data were obtained for 20,422 patients during the period of 2005 to 2012.

The researchers found that 43, 21, 12, 11, 10, 1, and 1% of patients started on second-line treatment with sulfonylurea (SU), basal insulin, thiazolidinedione (TZD), meglitinide, dipeptidyl peptidase-4 inhibitor (DPP-4i), glucagon-like peptide-1 receptor agonist, and acarbose, respectively. The risk of mortality was higher for basal insulin and lower for TZD compared with SU (hazard ratios, 1.18 and 0.76, respectively). Significantly lower risks of cardiovascular disease, fatal cardiovascular disease, coronary heart disease, fatal coronary heart disease, and congestive heart failure were seen for DPP-4i.

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“This nationwide observational study showed that second-line treatment with TZD and DPP-4i as add-on medication to metformin were associated with significantly lower risks of mortality and cardiovascular events compared with SU, whereas basal insulin was associated with a higher risk of mortality,” the authors write.

One author is employed by the Swedish Medical Products Agency. Two authors disclosed financial ties to the pharmaceutical industry.

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1. Ekström N, Svensson A, Miftaraj M, et al. Cardiovascular Safety of Glucose-Lowering Agents as Add-on Medication to Metformin Treatment in Type 2 Diabetes: Report from the Swedish National Diabetes Register (NDR). Diabetes, Obesity and Metabolism. doi:10.1111/dom.12704.