Arwa Younis1,2, Dana Eskenazi3, Ronen Goldkorn4,3, Jonathan Leor4,3, Nili Naftali-Shani4,3, Enrique Z Fisman3,5, Alexander Tenenbaum4,3,5, Ilan Goldenberg4,3,6, Robert Klempfner4,3. 1. The Leviev Heart Center, Sheba Medical Center, Tel Hashomer, Sheba Road 2, 52620, Ramat Gan, Israel. or.younis@gmail.com. 2. Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel. or.younis@gmail.com. 3. Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel. 4. The Leviev Heart Center, Sheba Medical Center, Tel Hashomer, Sheba Road 2, 52620, Ramat Gan, Israel. 5. Cardiovascular Diabetology Research Foundation, Holon, Israel. 6. Heart Research Follow-up Program, University of Rochester, Rochester, NY, USA.
Abstract
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 interleukin-1ß (IL-1ß, 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-1ß, hsCRP, and HbA1c were significantly lower in the intervention group as compared with the control group. There was a continuous elevation of IL-1ß 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-1ß elevation during follow up. A significant relative reduction of hsCRP and HbA1c in the intervention group was also observed. Trial registration NCT01604213.
RCT Entities:
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 interleukin-1ß (IL-1ß, 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-1ß, hsCRP, and HbA1c were significantly lower in the intervention group as compared with the control group. There was a continuous elevation of IL-1ß 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-1ß elevation during follow up. A significant relative reduction of hsCRP and HbA1c in the intervention group was also observed. Trial registration NCT01604213.
Authors: Arpeeta Sharma; Mitchel Tate; Geetha Mathew; James E Vince; Rebecca H Ritchie; Judy B de Haan Journal: Front Physiol Date: 2018-02-20 Impact factor: 4.566
Authors: Eilon Ram; Jacob Lavee; Alexander Tenenbaum; Robert Klempfner; Enrique Z Fisman; Elad Maor; Tal Ovdat; Sergei Amunts; Leonid Sternik; Yael Peled Journal: Cardiovasc Diabetol Date: 2019-09-16 Impact factor: 9.951