AIMS: To study the effects of saxagliptin, a dipeptidyl peptidase-4 inhibitor, on glycaemic stability and β-cell function in the SAVOR-TIMI 53 trial. METHODS: We randomized 16,492 patients with type 2 diabetes (T2D) tosaxagliptin or placebo, added to current antidiabetic medications, and followed them for a median of 2.1 years. Glycaemic instability was defined by: (i) a glycated haemoglobin (HbA1c) increase of ≥ 0.5% post-randomization; (ii) the initiation of new antidiabetic medications for ≥ 3 months; or (iii) an increase in dose of oral antidiabetic medication or ≥ 25% increase in insulin dose for ≥ 3 months. β-cell function was assessed according to fasting homeostatic model 2 assessment of β-cell function (HOMA-2β) values at baseline and at year 2 in patients not treated with insulin. RESULTS: Compared with placebo, participants treated with saxagliptin had a reduction in the development of glycaemic instability (hazard ratio 0.71; 95% confidence interval 0.68-0.74; p < 0.0001). In participants treated with saxagliptin compared with placebo, the occurrence of an HbA1c increase of ≥ 0.5% was reduced by 35.2%; initiation of insulin was decreased by 31.7% and the increases in doses of an oral antidiabetic drug or insulin were reduced by 19.5 and 23.5%, respectively (all p < 0.0001). At 2 years, HOMA-2β values decreased by 4.9% in participants treated with placebo, compared with an increase of 1.1% in those treated with saxagliptin (p < 0.0001). CONCLUSIONS:Saxagliptin improved glycaemia and prevented the reduction in HOMA-2β values. Saxagliptin may reduce the usual decline in β-cell function in T2D, thereby slowing diabetes progression.
RCT Entities:
AIMS: To study the effects of saxagliptin, a dipeptidyl peptidase-4 inhibitor, on glycaemic stability and β-cell function in the SAVOR-TIMI 53 trial. METHODS: We randomized 16,492 patients with type 2 diabetes (T2D) to saxagliptin or placebo, added to current antidiabetic medications, and followed them for a median of 2.1 years. Glycaemic instability was defined by: (i) a glycated haemoglobin (HbA1c) increase of ≥ 0.5% post-randomization; (ii) the initiation of new antidiabetic medications for ≥ 3 months; or (iii) an increase in dose of oral antidiabetic medication or ≥ 25% increase in insulin dose for ≥ 3 months. β-cell function was assessed according to fasting homeostatic model 2 assessment of β-cell function (HOMA-2β) values at baseline and at year 2 in patients not treated with insulin. RESULTS: Compared with placebo, participants treated with saxagliptin had a reduction in the development of glycaemic instability (hazard ratio 0.71; 95% confidence interval 0.68-0.74; p < 0.0001). In participants treated with saxagliptin compared with placebo, the occurrence of an HbA1c increase of ≥ 0.5% was reduced by 35.2%; initiation of insulin was decreased by 31.7% and the increases in doses of an oral antidiabetic drug or insulin were reduced by 19.5 and 23.5%, respectively (all p < 0.0001). At 2 years, HOMA-2β values decreased by 4.9% in participants treated with placebo, compared with an increase of 1.1% in those treated with saxagliptin (p < 0.0001). CONCLUSIONS:Saxagliptin improved glycaemia and prevented the reduction in HOMA-2β values. Saxagliptin may reduce the usual decline in β-cell function in T2D, thereby slowing diabetes progression.