Table 2.
Key head-to-head studies of basal-insulin initiation in insulin-naive patients
| Study | Study details | Target | Titration algorithm | Titration frequency | Insulin starting dose | Insulin dose at EOS | HbA1c, % baseline | HbA1c, % at EOS | Hypoglycemia |
|---|---|---|---|---|---|---|---|---|---|
| Riddle 2003 [42] |
Gla-100 or NPH once daily for 24 weeks n = 756 |
≤ 100 mg/dL | Dose adjustment based on mean of self-monitored FPG values from preceding 2 days: ≥ 180 mg/dL ↑ 8 U insulin; 140–180 mg/dL ↑ 6 U; 120–140 mg/dL ↑ 4 U; 100–120 mg/dL ↑ 2 U | Weekly | 10 U | Gla-100 47.2 U; NPH 41.8 U | Gla-100 8.61; NPH 8.56 | Gla-100 6.96; NPH 6.97 | Gla-100 9.2/patient year; NPH 12.9/patient year |
|
LANMET Yki-Järvinen 2006 [66] |
Gla-100 or NPH once daily before bedtime for 36 weeks n = 110 |
72–100 mg/dL | Dose adjustment based on mean pre-breakfast SMPG over 3 consecutive days: > 100 mg/dL ↑ 2 U; > 180 mg/dL ↑ 4 U | Not stated | 10 U for patients using metformin alone; 20 U if patients had used both sulfonylurea and metformin | Gla-100 68 U (0.69 U/kg); NPH 70 U (0.66 U/kg) | Gla-100 9.13; NPH 9.26 | Gla-100 7.14; NPH 7.16 | Gla-100 5.4/patient year; NPH 8.0/patient year |
| Hermansen 2006 [50] |
Insulin detemir or NPH twice daily for 24 weeks n = 476 |
≤ 108 mg/dL (pre-breakfast and pre-dinner) | Dose adjustment based on average of 3 preceding SMPG levels on consecutive days: > 180 mg/dL ↑ 10 U (responders and non-responders); 163–180 mg/dL ↑ 6 U (responders) ↑ 8 U (non-responders); 145–162 mg/dL ↑ 4 U (responders) ↑ 6 U (non-responders); 127–144 mg/dL ↑ 2 U (responders) ↑ 4 U (non-responders); 109–126 mg/dL ↑ 2 U (responders and non-responders); if one pre-breakfast plasma glucose: 56–72 mg/dL ↓ 2; < 56 mg/dL ↓ 4 | At least weekly for 12 weeks and at least fortnightly thereafter | 10 U per injection | Detemir 36.1 U pre-breakfast and 29.5 U in the evening; NPH 25.3 U pre-breakfast and 19.7 U in the evening | Detemir 8.6; NPH 8.5 | Detemir 6.8; NPH 6.6 | Detemir 8.6/patient year; NPH 15.95/patient year |
| Rosenstock 2008 [67] |
Insulin detemir (once or twice daily) or Gla-100 (once daily) for 52 weeks n = 582 |
≤ 108 mg/dL | Dose adjustments in 2-U steps in the evening according to average pre-breakfast SMPG and response to previous dose adjustment; morning dose adjustment according to average pre-dinner SMPG in some insulin detemir patients | Daily | 12 U | Detemir 0.78 U/kg (once daily 0.52 U/kg, twice daily 1.00 U/kg); Gla-100 0.44 U/kg | Detemir 8.64; Gla-100 8.62 | Detemir 7.16 (once daily 7.12, twice daily 7.06); Gla-100 7.12 | Detemir 5.8/patient year; Gla-100 6.2/patient year |
|
BEGIN ONCE LONG Zinman 2012 [61] |
IDeg 100 U or Gla-100 100 U once daily for 52 weeks Inadequately controlled with OADs n = 1030 |
70–88 mg/dL | Dose adjustment on the basis of the average of pre-breakfast SMPG values of 3 consecutive days preceding a visit (full details not given) | Not reported | 10 U | IDeg 0.59 U/kg; Gla-100 0.60 U/kg | 8.2 for both | IDeg 7.1; Gla-100 7.0 | IDeg 1.52/patient year; Gla-100 1.85/patient year |
|
BEGIN LOW VOLUME Gough 2013 [62] |
IDeg 200 U or Gla-100 100 U once daily for 26 weeks n = 457 |
< 90 mg/dL | Dose adjustment according to the average of 3 consecutive preceding pre-breakfast SMPG levels: < 56 mg/dL ↓ 4 U; 56–69 mg/dL ↓ 2 U; 70–89 mg/dL no change; 90–125 mg/dL ↑ 2 U; 126–143 mg/dL ↑ 4 U; 144–161 mg/dL ↑ 6 U; ≥ 162 mg/dL ↑ 8 U | Weekly | 10 U | IDeg 0.53 U/kg; Gla-100 0.60 U/kg | IDeg 8.3; Gla-100 8.2 | Mean HbA1c decreased by 1.3% in both treatment groups | IDeg 1.22/patient year; Gla-100 1.42/patient year |
|
BEGIN FLEX Meneghini 2013 [63] |
IDeg 100 U once-daily in a pre-specified dosing schedule (8–40-h intervals between injections) or IDeg 100 U once-daily IDeg at the main evening meal or Gla-100 at the same time each day for 26 weeks Insulin-naive or -experienced n = 610 |
70–90 mg/dL | Dose adjustment according to the average of 3 consecutive preceding pre-breakfast SMPG levels: < 56 mg/dL ↓ 4 U; 56–69 mg/dL ↓ 2 U; 70–89 mg/dL no change; 90–125 mg/dL ↑ 2 U; 126–143 mg/dL ↑ 4 U; 144–161 mg/dL ↑ 6 U; ≥ 162 mg/dL ↑ 8 U | Weekly | 10 U in insulin-naive patients | 0.6 U/kg for all groups in insulin-experienced patients; 0.5 U/kg for all groups in insulin-naive patients |
IDeg flexible dosing 8.5; IDeg fixed 8.4; Gla-100 8.4 |
IDeg flexible dosing mean decrease by 1.28; IDeg fixed 1.07; Gla-100 1.26 | IDeg flexible dosing 3.6/patient year; IDeg fixed 3.6/patient year; Gla-100 3.5/patient year |
| Meneghini 2013 [68] |
Insulin detemir or Gla-100 for 26 weeks n = 457 |
≤ 90 mg/dL |
Dose adjustment based on mean of 3 consecutive pre-breakfast SMPG measurements: 92–144 mg/dL ↑ 2 U; for each 18 mg/dL above that range (but ≤ 180 mg/dL), ↑ 2 U, with a maximum of 8 U added if mean FPG was >180 mg/dL. No dose adjustment was made if mean FPG was > 71 to ≤ 90 mg/dL, with no value ≤ 71 mg/dL without an obvious explanation The dose was to be reduced by 2 U if ≥ 1 fasting SMPG readings were 56–71 mg/dL and by 4 U if < 56 mg/dL |
Weekly | 10 U | Detemir 57 U (0.7 U/kg); Gla-100 51 U (0.61 U/kg) | Detemir 7.96; Gla-100 7.86 | Detemir 7.48; Gla-100 7.13 | Detemir 3.19/patient year; Gla-100 4.41/patient year |
| Onishi 2013 [64] |
IDeg or Gla-100 100 U once daily for 26 weeks n = 435 |
70–90 mg/dL | Dose adjustment based on mean of 3 consecutive pre-breakfast SMPG measurements: < 56 mg/dL ↓ 4 U; 56–69 mg/dL ↓ 2 U; 70–89 mg/dL no change; 90–125 mg/dL ↑ 2 U; 126–143 mg/dL ↑ 4 U; 144–161 mg/dL ↑ 6 U; ≥ 162 mg/dL ↑ 8 U | Weekly | 10 U | IDeg 19 U (0.28 U/kg); Gla-100 24 U (0.35 U/kg) | IDeg 8.4; Gla-100 8.5 | IDeg 7.2; Gla-100 7.1 | IDeg 3.0/patient year; Gla-100 3.7/patient year |
|
BEGIN EASY AM; BEGIN EASY PM Zinman 2013 [53] |
IDeg 200 U three times weekly, either before breakfast (AM) or with the evening meal (PM), or Gla-100 once daily n = 927 |
70–90 mg/dL | Based on mean pre-breakfast SMPG (lowest value from prior 3 consecutive days) IDeg: < 56 mg/dL ↓ 8 U; 56–69 mg/dL ↓ 4 U; 70–89 mg/dL no change; 90–125 mg/dL ↑ 4 U; 126– 143 mg/dL ↑ 8 U; 144–161 mg/dL ↑ 12 U; ≥ 162 mg/dL ↑ 16 U Gla-100: < 56 mg/dL ↓ 4U; 56–69 mg/dL ↓ 2 U; 70–89 mg/dL no change; 90–125 mg/dL ↑ 2 U; 126–143 mg/dL ↑ 4 U; 144–161 mg/dL ↑ 6 U; ≥ 162 mg/dL ↑ 8 U | Weekly | IDeg 20 U; Gla-100 10 U |
IDeg AM 50 U; Gla-100 62 U IDeg PM 51 U; Gla-100 56 U (mean calculated dose for IDeg vs actual dose for Gla-100) |
IDeg AM 8.2; Gla-100 8.3 IDeg PM 8.3; Gla-100 8.3 |
IDeg AM mean decrease of 0.93; Gla-100 1.28 IDeg PM mean decrease of 1.09; Gla-100 1.35 |
(Confirmed) IDeg AM 1.3/patient year; Gla-100 1.2/patient year IDeg PM 1.6/patient year; Gla-100 1.0/patient year |
|
EDITION 3 Bolli 2015 [55] |
Gla-300 or Gla-100 once-daily for 6 months n = 878 |
80–100 mg/dL | SMPG > 100 and < 140 mg/dL ↑ 3 U; SMPG ≥ 140 mg/dL ↑ 6 U; SMPG ≥ 60 and < 80 mg/dL ↓ 3 U; SMPG < 60 mg/dL or if severe or multiple symptomatic hypoglycemia events occurred ↓ ≥ 3 U at investigator’s discretion | Weekly | 0.2 U/kg/day | Gla-300 0.62 U/kg; Gla-100 0.53 U/kg | Gla-300 8.49; Gla-100 8.58 | Gla-300 7.08; Gla-100 7.05 | ≥ 1 confirmed (≤ 3.9 mmol/L) or severe hypoglycemia event: Gla-300 46%; Gla-100 53% |
EOS end of study, FPG fasting plasma glucose, Gla-100 insulin glargine 100 U/mL, Gla-300 insulin glargine 300 U/mL, HbA1c glycated hemoglobin A1c, IDeg insulin degludec, Gla-100 insulin glargine, NPH neutral protamine Hagedorn insulin, SMPG self-monitored plasma glucose