Efficacy and safety of insulin detemir once daily in combination with sitagliptin and metformin: the TRANSITION randomized controlled trial

Methods: In a 26-week, open-label, randomized, parallel-group study in type 2 diabetes, insulin-naive subjects concomitantly treated with MET +/- second oral antidiabetic drug (OAD) were randomized 1 : 1 to IDet + SITA + MET or SITA + MET +/- SU. All continued with MET treatment, and those treated with SU continued if randomized to SITA + MET +/- SU. Efficacy endpoints included glycosylated haemoglobin (HbA1c), fasting plasma glucose (FPG), 9-point self-measured plasma glucose (SMPG), weight, body mass index (BMI). Safety endpoints included adverse events (AEs) and hypoglycaemia. Results: Significantly higher reductions in HbA1c, FPG and SMPG were achieved with IDet + SITA + MET compared with SITA + MET +/- SU. Estimated HbA1c decreased by 1.44% in the IDet + SITA + MET group versus 0.89% in SITA + MET +/- SU, p < 0.001. FPG decreased by 3.7 mmol/l (66.3 mg/dl) versus 1.2 mmol/l (22.2 mg/dl), p < 0.001, respectively. Small decreases in weight and BMI were observed in both arms, with no significant differences. AEs were mild or moderate and were more common in the SITA + MET +/- SU arm than in the IDet + SITA + MET arm. There was no major hypoglycaemia. Observed rates of hypoglycaemia were very low (1.3/1.7 episodes/patient year) in both arms. The subgroup treated with MET and SUs prior to the trial achieved similar results. Conclusions: The combination of once-daily IDet with SITA showed a clinically and significantly better improvement in glycaemic control than SITA in combination with or without SUs. Both regimens were associated with a low rate of hypoglycaemia and slight weight reduction.