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Feature Articles

Practical Guidance on Effective Basal Insulin Titration for Primary Care Providers

  1. Louis Kuritzky1,
  2. Timothy S. Reid2 and
  3. Carol H. Wysham3
  1. 1University of Florida, Gainesville, FL
  2. 2Mercy Diabetes Center, Janesville, WI
  3. 3MultiCare Rockwood Diabetes & Endocrinology Center, Spokane, WA
  1. Corresponding author: Louis Kuritzky, lkuritzky{at}aol.com
Clinical Diabetes 2019 Oct; 37(4): 368-376. https://doi.org/10.2337/cd18-0091
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Article Figures & Tables

Tables

  • TABLE 1.

    Recommendations for Basal Insulin Therapy Initiation

    Treatment GuidelinesStarting Dose of InsulinInsulin Dose IncrementsFrequencyMaximum Insulin DoseTarget FPG, mg/dL
    ADA/EASD (1,3)10 units/day or 0.1−0.2 units/kg/day5−15% or 1−4 units1−2 times per week0.5 units/kg/day80–130
    AACE/ACE (2)0.1−0.2 units/kg/day for A1C <8.0%; 0.2−0.3 units/kg/day for A1C >8.0%2 units for fixed regimenEvery 2−3 days—<110*
    IDF (18)—2 unitsEvery 3 days—<115
    • ↵* Target FBG. IDF, International Diabetes Federation.

  • 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.

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Practical Guidance on Effective Basal Insulin Titration for Primary Care Providers
Louis Kuritzky, Timothy S. Reid, Carol H. Wysham
Clinical Diabetes Oct 2019, 37 (4) 368-376; DOI: 10.2337/cd18-0091

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Practical Guidance on Effective Basal Insulin Titration for Primary Care Providers
Louis Kuritzky, Timothy S. Reid, Carol H. Wysham
Clinical Diabetes Oct 2019, 37 (4) 368-376; DOI: 10.2337/cd18-0091
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