TABLE 2.

Studies Comparing Basal Insulin Titration Protocols

StudyProtocol Description
INITIATE (25)Type of titration: patient-driven; in groups of four to eight patients or individually
Insulin: insulin glargine 100 units/mL
Starting dose: 10 units/day at bedtime
Frequency of dose adjustment: every 3 days based on FPG values for 3 consecutive days
Algorithm: +2 to +4 units if FPG >100 mg/dL; −2 units if FPG <72 mg/dL and presence of symptomatic hypoglycemia with no apparent cause
Target FPG: 72−100 mg/dL
Main findings: similar A1C levels and incidence of hypoglycemia, but greater weight gain (+3.7 vs. +2.2 kg, P <0.02) for titration in groups versus individual titration; similar treatment satisfaction rates, but less total time spent with titration visits/phone calls (−48%) for titration in groups versus individual titration
GOAL A1C (27)Type of titration: patient-driven, with no unsolicited physician contact between visits (standard titration) or weekly contact (active titration)
Insulin: insulin glargine 100 units/mL
Starting dose: 10 units/day at bedtime
Frequency of dose adjustment: weekly and at every visit (every 6 weeks) based on the mean FBG of the previous 2–4 days
Algorithm: +0 to +2 units if 120 mg/dL <FBG ≥100 mg/dL; +2 units if 140 mg/dL <FBG ≥120 mg/dL; +4 units if 160 mg/dL <FBG ≥140 mg/dL; +6 units if 180 mg/dL <FBG ≥160 mg/dL; +8 units if FBG ≥180 mg/dL; decrease to previous lower dose if FBG <70 mg/dL
Target FPG: 70−100 mg/dL
Main findings: greater A1C reduction (1.5 vs. 1.3%, P <0.0001) for active titration versus standard titration; greater incidence of hypoglycemia (6.0 vs. 3.7 episodes/patient-year, P = 0.001) for active titration versus standard titration
AT.LANTUS (28)Type of titration: patient-driven and physician-led
Insulin: insulin glargine 100 units/mL
Starting dose: 10 units/day (or numerically equivalent to the highest FBG over the previous 7 days for self-titration) at bedtime
Frequency of dose adjustment: weekly (physician-led titration) or every 3 days for self-titration (patient-driven titration) based on mean FBG value for the prior 3 consecutive days
Algorithm: +0 to +2 units/day if 120 mg/dL > FBG ≥100 mg/dL; +2 units/day if 140 mg/dL > FBG ≥120 mg/dL; +4 units/day (+2 units/day for self-titration) if 180 mg/dL > FBG ≥140 mg/dL; +6 to +8 units/day (+2 units/day for self-titration) if FBG ≥180 mg/dL
Target FPG: ≤100 mg/dL
Main findings: higher hypoglycemia (33.3 vs. 29.8%, P <0.01), but greater A1C reduction (−1.22 vs. −1.08%, P <0.001) for self-titration vs. physician-led titration
ATLAS (29)Type of titration: patient-driven and physician-led; Asian patients
Insulin: insulin glargine 100 units/mL
Starting dose: 10 units/day (8−10 units/day in India and 4 units/day in Japan) at bedtime
Frequency of dose adjustment: at every visit (physician-led titration) or twice per week (self-titration) based on intermediate value of last three consecutive measurements
Algorithm: dose decrease at physician’s discretion if FBG ≤56 mg/dL; −2 units if FBG ≤70 mg/dL or symptomatic hypoglycemia; no adjustment if 70 mg/dL <FBG ≤110 mg/dL; +2 units if 110 mg/dL<FBG ≤160 mg/dL; +4 units if FBG >160 mg/dL
Target FPG: 110 mg/dL
Main findings: greater A1C reduction (−1.40 vs. −1.25%, P = 0.043) and higher incidence of nocturnal hypoglycemia (16.4 vs. 6.5%, P = 0.002) and symptomatic hypoglycemia (36.0 vs. 25.6%, P = 0.02) for self-titration versus physician-led titration; similar weight gain and treatment satisfaction
PREDICTIVE 303 (26)Type of titration: patient-driven and physician-led
Insulin: insulin detemir 100 units/mL
Starting dose: not reported
Frequency of dose adjustment: every 3 days based on the mean of three adjusted* FPG measurements (self-titration)
Algorithm: −3 units if adjusted FPG <80 mg/dL; no adjustment if 80 mg/dL <adjusted FPG <110 mg/dL; +3 units if adjusted FPG >110 mg/dL
Target FPG: 80−100 mg/dL
Main findings: similar weight gain, but greater A1C reduction (−0.6 vs. −0.5%, P = 0.0106) and incidence of hypoglycemia (6.44 vs. 4.95%, P <0.0001) for patients self-titrating vs. physician-led titration
BEGIN (23)Type of titration: patient-driven
Insulin: insulin degludec 100 units/mL
Starting dose: 10 units/day, with an interval of 8−40 hours between injections
Frequency of dose adjustment: weekly, based on one FBG value (simple titration) or on the lowest of three consecutive FBG values (stepwise titration)
Algorithm: −4 units if FBG <56 mg/dL; −2 units if 56 mg/dL < FBG <70 mg/dL (stepwise titration only); no adjustment if 71 mg/dL <FBG <90 mg/dL; +4 units (simple titration) or +2 units (stepwise titration) if 91 mg/dL <FBG <126 mg/dL; +4 units if 127 mg/dL <FBG <144 mg/dL (stepwise titration only); +6 units if 145 mg/dL <FBG <162 mg/dL (stepwise titration only); +8 units if FBG >162 mg/dL (stepwise titration only)
Target FPG: 71−90 mg/dL
Main findings: similar A1C reduction, incidence of hypoglycemia, and weight change
TITRATION (24)Type of titration: physician-led (as in the EDITION studies [32]) and patient-driven (as in the INSIGHT study [30,31])
Insulin: insulin glargine 300 units/mL
Starting dose: 0.2 units/day for insulin-naive patients, or pre-study dose for patients receiving once-daily insulin glargine 100 units/mL, insulin detemir or NPH, or 80% of pre-study dose for patients receiving twice-daily insulin detemir or NPH, in the evening
Frequency of dose adjustment: at least once weekly, but not more than every 3 days (EDITION) based on median FPG from the previous 3 days; daily (INSIGHT)
Algorithm: EDITION: +6 units/day if FPG ≥140 mg/dL; +3 units/day if 100 mg/dL <FPG <140 mg/dL; no adjustment if FPG 80−100 mg/dL; −3 units/day if 60 <FPG <80 mg/dL; −3 units/day if FPG <60 mg/dL or occurrence of two or more symptomatic or one severe hypoglycemia event in the previous week; INSIGHT: +1 unit/day if FPG ≥100 mg/mL
Target FPG: 80–100 mg/dL
Main findings: similar A1C reduction (−0.8% for both algorithms), incidence of hypoglycemia, and weight change (+0.1 vs. +0.4 kg for EDITION and INSIGHT, respectively); similar treatment satisfaction rate, but 86% of health care providers preferred the INSIGHT algorithm because of its simplicity, effectiveness, and safety
  • * Adjusted FPG was capillary blood glucose level calibrated to equivalent plasma glucose values. AT.LANTUS, A Trial Comparing Lantus Algorithms to Achieve Normal Blood Glucose Targets in Subjects With Uncontrolled Blood Sugar; ATLAS, Asian Treat to Target Lantus Study; GOAL A1C, Glycemic Optimization with Algorithms and Labs at Point of Care; INITIATE, Initiate Insulin by Aggressive Titration and Education; INSIGHT, Implementing New Strategies with Insulin Glargine for Hyperglycaemia Treatment; PREDICTIVE, Predictable Results and Experience in Diabetes through Intensification and Control to Target: An International Variability Evaluation.