• β-cell function;
  • hypoglycaemia;
  • insulin;
  • sitagliptin;
  • weight gain

Aim: Individuals requiring insulin therapy for type 2 diabetes often require escalation of their regimen to achieve glycaemic control. Optimal management strategies for uncontrolled type 2 diabetes would improve glycaemic control without hypoglycaemia and weight gain. This study compared the efficacy and tolerability of adding sitagliptin, an oral dipeptidyl peptidase-4 inhibitor, and an up to 20% increase in insulin dose in patients with uncontrolled type 2 diabetes on insulin therapy.

Methods: We conducted a 24-week, randomized, active-competitor, parallel-group study in subjects with uncontrolled type 2 diabetes [haemoglobin A1c (HbA1c) = 7.5–11%] currently using insulin therapy. Subjects were randomly assigned to either the sitagliptin adding (100 mg daily, n = 70) or an insulin-increasing arm (≥10% at week 12 and ≥10% at week 24, n = 70) while continuing other medications.

Results: Average baseline HbA1c was 9.2% in both groups. HbA1c decreased more at 24 weeks in the sitagliptin adding than the insulin-increasing arm (−0.6 ± 0.1% vs. −0.2 ± 0.1%, p < 0.01). Insulin was increased by 25% at 24 weeks in the insulin-increasing group. Hypoglycaemic events were less common and less severe in sitagliptin adding arm than insulin-increasing arm (7.0 vs. 14.3 events per patient-year, p < 0.05). Weight was stable in the sitagliptin adding subjects (68.6 ± 11.6 vs. 68.1 ± 11.4 kg) but increased in the insulin-increasing subjects (66.2 ± 10.6 vs. 67.4 ± 9.7 kg, p < 0.05). Other adverse events occurred at similar rates in both arms.

Conclusions: Compared to a 25% increase in insulin dose, adding sitagliptin to an insulin-based regimen was more effective at lowering HbA1c and associated with less hypoglycaemia and weight gain over 24 weeks. Clinical trial number: NCT01100125.