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Alogliptin Prevents the Progression of Atherosclerosis in Type 2 Diabetes Patients

New study suggests possible role for DPP-4 inhibitor in reducing CVD risk.

When treating patients with type 2 diabetes, it is important to reduce the risk of developing Editcardiovascular disease (CVD). Previous studies have shown that higher HbA1c values are risk factors for CVD. However, previous studies have not shown that glycemic control or treatment with any oral hypoglycemic agent reduces incidence of CVD.

Recent studies have shown that dipeptidyl peptidase 4 (DPP-4) inhibitors have antiatherosclerotic benefits. The purpose of a new study is to investigate the effects of alogliptin on the intima-media thickness (IMT) in diabetes patients that are not believed to have CVD.

This is a prospective, randomized, open-label, blinded-end point, multicenter, parallel-group, comparative study that included 341 patients with diabetes and no history of CVD. The primary outcomes were change in right and left maximum IMT of the common carotid artery (max-IMT-CCA) and mean IMT of the common carotid artery (mean-IMT-CCA). The primary outcomes were measured by carotid arterial echography; the measurements were taken at the start of the study then repeated at 52 weeks and 104 weeks. They looked at several secondary outcomes:

  1. changes in parameters related to glycemic control (HbA1c, fasting glucose levels);
  2. changes in lipid panels (HDL, LDL, total cholesterol and triglycerides);
  3. changes in parameters related to kidney failure (albumin excretion and eGFR);
  4. Occurrence of CV events (sudden death, heart disease and stroke); and
  5. Adverse effects related to medication.

After data was collected statistical analysis was performed on the primary end point using the mixed-effects model for repeated measures with treatment group, and base-line IMT as fixed-effects. An unstructured covariate was used to model the covariance within subject variability. Occurrence of CV events was analyzed using a log-rank test and a Cox proportional hazards model. Baseline and follow-up group comparisons were assessed using the Wilcoxan rank sum test for continuous variables and the Fisher exact test for categorical variables. A Fisher exact test was used to compare the number and percentage of patients reporting adverse effects.

The results of this study showed that patients in the alogliptin group had more glucose-lowering effect than the conventional treatment (-0.3 ± 0.7% vs. -0.1 ± 0.8%,P=0.004). In addition, patients in the alogliptin group had greater A1c reduction than the conventional group. When it comes to changes in the mean-IMT-CCA (-0.026mm vs 0.005 mm) and max-IMT-CCA (right: -0.045mm vs 0.011mm and left: -0.079mm vs -0.015 mm) patients in the alogliptin group had significantly greater changes. This would indicate that alogliptin has an effect on max and mean-IMT-CCA as well as A1c reductions. Alogliptin treatment stopped the progression of carotid IMT in patients with diabetes who do not have cardiovascular disease when compared to conventional treatment. Future studies are needed over a longer period of time to see if CVD develops in these patients.

Practice Pearls:

  • This study was performed to confirm suspicions about the potential antiatherosclerotic benefits of alogliptin.
  • Alogliptin may be a good choice for diabetes patients who do not have a history of  CVD.
  • Alogliptin and other DPP-4 inhibitors have substantial A1c lowering capabilities without causing hypoglycemia.

 

Mita T, Katakami N, Yoshii H, et al. Alogliptin, a Dipeptidyl Peptidase 4 Inhibitor, Prevents the Progression of Carotid Atherosclerosis in Patients with Type 2 Diabetes: The Study of Preventive Effects of Alogliptin on Diabetic Atherosclerosis (SPEAD-A). Diabetes Care January 2016 39:1 139-148; doi:10.2337/dc15-0781


Researched and prepared by Jennifer Zahn, Doctor of Pharmacy Candidate University Of South Florida College of Pharmacy, reviewed by Dave Joffe, BSPharm, CDE