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

• Published in: Diabetes, obesity & metabolism Vol. 13; no. 3; pp. 268 - 275
• Main Authors: Hollander, P, Raslova, K, Skjøth, T.V, Råstam, J, Liutkus, J.F
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.03.2011; Wiley Subscription Services, Inc
• Subjects: Antidiabetics; Body mass index; Diabetes; diabetes mellitus; Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Type 2 - blood; Diabetes Mellitus, Type 2 - drug therapy; Drug Administration Schedule; Drug Therapy, Combination; efficacy; Female; Glycated Hemoglobin A - drug effects; Hemoglobin; Humans; Hypoglycemia; Hypoglycemia - drug therapy; Hypoglycemia - prevention & control; Hypoglycemic Agents - administration & dosage; Hypoglycemic Agents - pharmacology; Insulin; Insulin - administration & dosage; Insulin - analogs & derivatives; Insulin - pharmacology; Insulin Detemir; Insulin, Long-Acting; Male; Metformin; Metformin - administration & dosage; Metformin - pharmacology; Middle Aged; once daily; Pyrazines - administration & dosage; Pyrazines - pharmacology; Safety; sitagliptin; Sitagliptin Phosphate; sulphonylurea; Treatment Outcome; Triazoles - administration & dosage; Triazoles - pharmacology; Weight; Weight Loss - drug effects
• ISSN: 1462-8902; 1463-1326
• DOI: 10.1111/j.1463-1326.2010.01351.x

Aim: The aim of this trial was to evaluate the efficacy and safety of the combination of once-daily insulin detemir (IDet) and sitagliptin (SITA) versus SITA ± sulphonylurea (SU), both in combination with metformin (MET) in insulin-naive subjects. 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.