Introduction 1c 1 3 4 5 1c 5 7 8 1 9 13 14 15 11 16 17 16 Methods Study protocol 1 18 1c Table 1 Algorithm used for insulin dose titration Algorithm Adjustment of insulin dose (U) If positive response to previous dose adjustment a Evening insulin dose adjustment  Average pre-breakfast self-monitored PG   >10.0 mmol/l +12 +12   9.1–10.0 mmol/l +8 +10   8.1–9.0 mmol/l +6 +8   7.1–8.0 mmol/l +4 +6   6.1–7.0 mmol/l +2 +2  If one self-monitored PG measurement   3.1–4.0 mmol/l −2 –2   <3.1 mmol/l −4 –4 b  Average pre-dinner self-monitored PG   >10.0 mmol/l +8 +8   9.1–10.0 mmol/l +6 +8   8.1–9.0 mmol/l +4 +6   7.1–8.0 mmol/l +2 +4   6.1–7.0 mmol/l +2 +2 If one self-monitored PG measurement   3.1–4.0 mmol/l –2 –2   <3.1 mmol/l –4 –4 a b +, insulin dose titrated up; –, insulin dose titrated down Participants 2 1c 1c Study medications Titration of basal insulin 1 Outcome measures 1c 1c Analyses and assessments 1c Statistical analyses 1c 1c 1c 1c 1c 1c Results Participants 1 1 2 1c n n Fig. 1 Patient disposition during the trial and consequent analysis sets  2 1c Table 2 Clinical characteristics of type 2 diabetic participants Characteristics Detemir Glargine n 291 (100) 291 (100) n 166/125 171/120 n Black 22 12 White 250 263 Asian-Pacific islander 7 7 Other 12 9 n Monotherapy 73 (25) 70 (24)  Metformin 32 (11) 33 (11)  Insulin secretagogues 41 (14) 37 (13) Combination therapy 218 (75) 221 (76)  Metformin + secretagogue 212 215  Metformin + alpha glucosidase inhibitor 3 1  Secretagogue + alpha glucosidase inhibitor 3 4  Secretagogue + secretagogue (SU + glinide) – 1 Age (years) 58.4 (10.2) 59.4 (9.6) a 87.4 (16.6) 87.4 (17.4) 2 30.6 (4.8) 30.5 (4.6) Duration of diabetes (years) 9.1 (6.1) 9.1 (6.4) 1c a 8.64 (0.78) 8.62 (0.77) C-peptide (nmol/l) 0.87 (0.56) 0.85 (0.55) n a SU, sulfonylurea Insulin dosing n n n n n Glycaemic control 1c n n 3 1c 3 1c 2 Fig. 2 1c a b  Table 3 Glycaemic control in type 2 diabetic patients treated with insulin detemir or insulin glargine   Detemir Glargine Difference (95% CI) (detemir/glargine) p Completers on once daily Completers on twice daily All All Parameters n Mean n Mean n Mean n Mean 1c a 104 7.12 (0.11) 127 7.06 (0.10) 268 7.16 (0.08) 275 7.12 (0.08) 0.05 (–0.11, 0.21) – a 104 7.27 (0.31) 127 6.73 (0.25) 268 7.14 (0.21) 272 6.98 (0.21) 0.16 (–0.26, 0.58) – 1c n 103 52 (51) 127 69 (54) 248 129 (52) 259 135 (52) – 1.00 1c n 103 31 (30) 127 48 (38) 248 82 (33) 259 90 (35) – 0.71 Within-participant variation (mmol/l)           b 103 0.93 (15.0) 125 1.15 (19.6) 238 1.06 (17.5) 257 1.03 (17.3) – 0.45 b 103 1.27 (19.8) 125 1.84 (26.4) 238 1.60 (23.6) 258 1.55 (22.0) – 0.41 a n b 3 n n 2 1c p p Hypoglycaemia 4 1c Table 4 Hypoglycaemic episodes in type 2 diabetic patients treated with insulin detemir or insulin glargine Events   n n Relative risk (detemir/glargine) (95% CI) n n Rate (per patient-year) n n Rate (per patient-year) All 182 (63) 1521 5.8 191 (66) 1670 6.2 0.94 (0.71–1.25)  Nocturnal 95 (33) 352 1.3 93 (32) 350 1.3 1.05 (0.69–1.58) Major 5 (2) 9 0.0 8 (3) 8 0.0 –  Nocturnal 3 (1) 5 0.0 4 (1) 4 0.0 – Minor 135 (46) 737 2.9 151 (52) 786 2.9 1.05 (0.75–1.46)  Nocturnal 73 (25) 212 0.8 71 (24) 192 0.7 1.17 (0.75–1.83) Symptoms only 137 (47) 760 3.0 133 (46) 866 3.2 0.88 (0.61–1.25)  Nocturnal 48 (17) 128 0.5 49 (17) 151 0.6 0.88 (0.50–1.54) No statistical analyses were performed on the small numbers of major events. Body weight n n p n n p p n n 3 Fig. 3 p p  Adverse events and other safety measures 1 2 3 4 Discussion 12 13 19 20 14 15 21 22 The present study was designed to compare the two basal insulin analogues as they had been used in previous studies and according to label. Thus, insulin glargine was given once daily at bedtime regardless of glycaemic profile, while for insulin detemir an option was provided for adding a second dose, primarily based on pre-dinner blood glucose level following a structured insulin titration protocol. The decision to use twice-daily insulin detemir could not be attributed to hypoglycaemia, as patients who were switched to a twice-daily regimen had on average 3.7 hypoglycaemic episodes per patient-year prior to transfer, compared with 4.7 episodes per patient-year in patients completing treatment on once-daily insulin detemir. The frequency of nocturnal hypoglycaemia was also lower in relevant patients before transfer (0.7 vs 0.9 episodes per patient-year). 1c 13 1c 9 11 1c 1c 1c Electronic supplementary material Below is the link to the electronic supplementary material.
 ESM 1 (PDF 12.4 kb) ESM Table 1  Treatment emergent adverse events probably or possibly related to trial product by system organ class, ITT cohort (PDF 20.2 kb) ESM Table 2 Adverse events leading to withdrawal (PDF 17.2 kb) ESM Table 3 Treatment emergent serious adverse events by system organ class, ITT cohort (PDF 23.1 kb) ESM Table 4 Treatment emergent serious adverse events preferred term, occurring in more than one subject, ITT (PDF 14.6 )