The addition of vildagliptin to metformin prevents the elevation of interleukin 1β in patients with type 2 diabetes and coronary artery disease: a prospective, randomized, open-label study

Background: Patients with type 2 diabetes present with an accelerated atherosclerotic process. Animal evidence indicates that dipeptidyl peptidase-4 inhibitors (gliptins) have anti-inflammatory and anti-atherosclerotic effects, yet clinical data are scarcely available. Design and methods: A prospective, randomized, open-label study was performed in 60 patients with coronary artery disease (CAD) and type 2 diabetes, who participated in a cardiac rehabilitation program. After a washout period of 3 weeks, patients were randomized in a 2:1 ratio to receive combined vildagliptin/metformin therapy (intervention group: n = 40) vs. metformin alone (control group: n = 20) for a total of 12 weeks. Blinded assessment of interleukin1 beta (IL-1 beta, the primary endpoint), hemoglobin A1c (HbA1c), and high sensitivity C reactive protein (hsCRP), were performed at baseline and after 12 weeks. Results: Mean age of study patients was 67 +/- 9 years, 75% were males, and baseline HbA1c and inflammatory markers levels were similar between the two groups. At 12 weeks of follow up, levels of IL-1 beta, hsCRP, and HbA1c were significantly lower in the intervention group as compared with the control group. There was a continuous elevation of IL-1 beta among the control group, which was not observed in the intervention group (49 vs. 4%, respectively; p < 0.001). The hsCRP was lowered by 60% in the vildagliptin/metformin group vs. 23% in the metformin group (p < 0.01). Moreover, a significant relative reduction of the HbA1c was seen in the intervention group (7% reduction, p < 0.03). Conclusion: The addition of vildagliptin to metformin treatment in patients with type 2 diabetes and CAD led to a significant suppression of the IL-1 beta elevation during follow up. A significant relative reduction of hsCRP and HbA1c in the intervention group was also observed. Trial registration NCT01604213