Dapagliflozin (an inhibitor of the subtype 2 of the sodium-glucose transport proteins: SGLT2) alone and in combination with saxagliptin (an dipeptidyl peptidase-4 (DPP-4) inhibitor) has been shown to improve beta cell function and reduce insulin levels by increasing insulin clearance. This result of a comparative trial was reported at the Annual Meeting of the European Association for the Study of Diabetes 2015.
Elisabeth Adler-Ekholm, MD, of AstraZeneca, Molndal, Sweden, explained that dapagliflozin alone and in combination with saxagliptin has been shown to reduce, while saxagliptin increased, insulin levels during a meal tolerance test. Dr. Ekholm and colleagues determined whether this result was driven by increased insulin clearance.
C-peptide/insulin ratio was used as a marker for insulin clearance during a meal tolerance test, and β-cell function was assessed by homeostasis model assessment 2 in a study comparing saxagliptin 5 mg + dapagliflozin 10 mg vs saxagliptin and dapagliflozin alone in patients with type 2 diabetes poorly controlled with metformin.
At week 24, saxagliptin + dapagliflozin and saxagliptin increased mean C-peptide area under the curve from baseline, whereas no change was observed for dapagliflozin (saxagliptin + dapagliflozin: 40.2 [9.2, 71.3 ng/mL]; saxagliptin: 95.4 [63.4, 127.4] ng/mL; dapagliflozin: 14.5 [-17.6, 46.8] ng/mL).
In contrast, change from baseline in insulin area under the curve was reduced with saxagliptin + dapagliflozin (-1120.4 [-1633.9, -606.9] μU/mL), and dapagliflozin [-1018.6 (-1550.5, -486.8)], but increased with saxagliptin (661.2 [131.1, 1191.3] μU/mL).
Curves for C-peptide/insulin at baseline were similar between the three treatment groups. At week 24, C-peptide/insulin was unaltered by saxagliptin but increased similarly after saxagliptin + dapagliflozin and dapagliflozin, mainly due to decreased insulin area under the curve with dapagliflozin.
All treatments improved β-cell function compared with baseline (saxagliptin + dapagliflozin: 20.6% [16.5, 24.8]; dapagliflozin: 17.0% [12.7, 21.4]; saxagliptin: 11.0 % [6.6, 15.5]).
Dr. Ekholm concluded that the data suggest that at 24 weeks, saxagliptin + dapagliflozin and dapagliflozin improved β-cell function and increased insulin clearance in patients with type 2 diabetes poorly controlled with metformin.