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DPP-4 Inhibitor Saxagliptin May Slow Beta-cell Decline in Type 2

Mar 27, 2015

A multinational team of researchers studied data from over 16,000 patients in the SAVOR-TIMI 53 trial….

Saxagliptin (Onglyza) is a commonly prescribed dipeptidyl peptidase-4 inhibitor for the treatment of type 2 diabetes. An international team of researchers examined the effects of saxagliptin on glycemic stability and β-cell function in the SAVOR-TIMI 53 trial.

In this multinational double blind trial, 16,492 patients with type 2 diabetes were randomized to either saxagliptin or placebo, which were added to the patients’ current antidiabetic medications. The two randomized groups were then followed for a median of 2.1 years. Glycemic instability was defined by the following: (1) HbA1c increase of ≥0.5% post-randomization; (2) the initiation of new anti-diabetic medications for ≥3 months; or (3) an increase in dose of oral anti-diabetic medication or ≥25% increase in insulin dose for ≥3 months. In order to assess β-cell function, researchers used the fasting homeostatic model 2 assessment of β-cell function (HOMA-2β) values at baseline and then at the 2nd year in patients who were not treated with insulin.

When compared with placebo, the participants treated with saxagliptin were shown to have a reduction in the development of glycemic instability (hazard ratio 0.71; 95% confidence interval of 0.68–0.74; p < 0.0001). In participants treated with saxagliptin when compared with placebo, the occurrence of an HbA1c increase of ≥0.5% resulted in a reduction by 35.2%; the initiation of insulin was decreased by 31.7% and the increases in doses of any oral anti-diabetic drug or insulin were reduced by 19.5 and 23.5%, respectively (all resulted in p < 0.0001). At the 2 year mark, HOMA-2β values decreased by 4.9% in subjects who were treated with placebo, compared with an increase of 1.1% in those treated with saxagliptin (p < 0.0001).

The researchers concluded that saxagliptin did show improvement in glycemia and it also prevented the reduction in HOMA-2β values. Therefore, saxagliptin may help reduce the usual decline in β-cell function in type 2 diabetes patients, thereby slowing the progression of diabetes.

Practice Pearls:

  • Adverse events and serious adverse events as well as glycemic efficacy of saxagliptin in elderly patients are similar to those found in younger patients.
  • The SAVOR-TIMI 53 trial also supported the overall cardiovascular safety of saxagliptin during this study, although the risk of heart failure hospitalization was increased irrespective of age category.
  • The DPP-4 inhibitors are among the first antihyperglycemic agents to be assessed under the new FDA regulations.

G Leibowitz, A Cahn, DL Bhatt, et al. “Impact of Treatment with Saxagliptin on Glycaemic Stability and Beta-Cell Function in the SAVOR-TIMI 53 Study”. Diabetes Obes Metab 2015 Feb 25;[EPub Ahead of Print]