Insulin Dosing in Type 2 Diabetes

Aka: Insulin Dosing in Type 2 Diabetes, Insulin Dosing in Type II Diabetes

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II. Epidemiology

  1. Insulin is prescribed in only half of the estimated 15% of type 2 diabetics requiring Insulin (Worldwide)
    1. Basu (2019) Lancet Diabetes Endocrinol 7(1): 25-33 [PubMed]

III. Indications

  1. See Type II Diabetes Mellitus
  2. Precautions
    1. Insulin when indicated should be framed as a an adjunct to glycemic control, rather than a failure of therapy
    2. Continue GLP1 Agonist, SGLT2 Inhibitor and Metformin as Insulin is initiated
      1. In contrast, Sulfonylureas and Meglitinides are discontinued when Insulin started (esp. Bolus Insulin)
      2. DPP-4 Inhibitor may be considered for continuation
  3. Insulin is recommended when noninsulin therapy (esp. GLP1 Agonist, SGLT2 Inhibitor) fails to meet Blood Glucose goals
    1. See Noninsulin Therapy of Type 2 Diabetes
    2. High Insulin Resistance
      1. Severe chronic Hyperglycemia (mean Glucose >300 mg/dl, Hemoglobin A1C >12%)
      2. Significant Hyperglycemia symptoms
    3. Beta cell decompensation
      1. Longstanding, poorly controlled Type 2 Diabetes Mellitus
      2. Catabolism (Unintentional Weight Loss, Muscle wasting)
  4. Insulin Augmentation (Basal insulin only starting at 0.1 to 0.3 units/kg)
    1. Symptomatic Hyperglycemia or Hemoglobin A1C >9% despite non-Insulin therapy AND
      1. One or two oral Oral Hypoglycemic agents OR
      2. GLP-1 Agonist and at least one Oral Hypoglycemic agent
  5. Insulin Replacement (basal and Bolus Insulin starting at 0.6 to 1.0 units/kg)
    1. Blood Glucose >300 to 350 mg/dl OR
    2. Hemoglobin A1C >10-12% OR
    3. Failure to meet Blood Glucose goals despite Insulin Augmentation

IV. Adverse Effects

  1. Weight gain (80% of patients on Insulin introduction)
    1. Expect 0.4 kg/m2 increase in BMI
    2. Consider Basal insulin with GLP-1 Receptor Agonist, Metformin or Pamlintide to mitigate weight gain
    3. Avoid other Medications Associated with Weight Gain
  2. Hypoglycemia
    1. See Hypoglycemia Management in Diabetes Mellitus
    2. Patient Education on recognition and management of Hypoglycemia
    3. Exercise caution when Hemoglobin A1C <7.4%, severe Renal Insufficiency
    4. Do not use Insulin Secretagogues (e.g. Sulfonylureas, Meglitinide) with Bolus Insulin
    5. Analogue basal (e.g. Lantus) and bolus (e.g. Lispro) agents are lower risk for Hypoglycemia than regular and NPH

V. Protocol: Insulin Education

  1. Encourage multidisciplinary team care that can help maintain safe and effective Insulin use (and overall DM management)
    1. Nurses
    2. Pharmacists
    3. Diabetic educators
  2. Hypoglycemia prevention
    1. Cautious and thoughtful Insulin Dosing
    2. Glucose monitoring including Continuous Glucose Monitors
    3. Education on symptoms of Hypoglycemia and emergency treatment fo patient and Caregivers
      1. See Hypoglycemia Management in Diabetes Mellitus
  3. Injection education
    1. Insulin Pen use
    2. Differentiation of basal and Bolus Insulins
    3. Injection technique (e.g. squeeze skin, needle angle, Subcutaneous Injection)
    4. Safe needle disposal
    5. Injection site rotation
      1. Prevent injection site Lipodystrophy

VI. Protocol: Identify Blood Glucose goals

  1. No predisposition to Hypoglycemia (goals per ADA, and AACE/ACE in parentheses)
    1. Pre-meal or Fasting: 80-130 mg/dl per ADA (or 70 to 110 mg/dl per AACE/ACE)
    2. Two hour post-prandial Glucose <180 mg/dl per ADA (or 140 per AACE/ACE)
      1. Blood Glucose 20-40 mg/dl above pre-meal Glucose
    3. Bedtime: 100-140 mg/dl
    4. Continuous Glucose Monitor: >70% time in range 70-180 mg/dl
    5. Hemoglobin A1C: <6.5 to 7%
      1. Target in pregnancy is also <6.5-7%
  2. Predisposition for Hypoglycemia (Comorbid conditions, older patients, poor functional status, limited Life Expectancy)
    1. Pre-meal/Fasting: 100-150 mg/dl
    2. Hemoglobin A1C: <8 to 8.5%

VII. Protocol: Starting Basal Only Insulin (Augmentation) and Advancing to Basal/Bolus Insulin (Replacement) in Type II Diabetes

  1. Precautions
    1. Requires regular Blood Glucose Monitoring and compliant, reliable patient and family
    2. Educate on home Hypoglycemia Management (Glucose tablets, Glucagon)
  2. Step 0: 0-0-0-G (Basal Only Protocol - Insulin Augmentation)
    1. Basal insulin
      1. Preparations
        1. Insulin Glargine (G, e.g. Lantus)
        2. Caution with longer acting agents (>24 hours, titrate at >4 day intervals)
          1. Insulin Degludec (Tresiba)
          2. Insulin Glargine U-300 (Toujeo, Toujeo Max Solostar)
        3. NPH (if cost is a concern)
          1. Also start with single dose at bedtime (despite shorter half life)
      2. Starting dose options
        1. Basal insulin 10 units at night OR
        2. Basal insulin 0.1 to 0.2 units/kg/day (or 50% of total daily sliding scale dose)
          1. Some aggresive protocols use 0.2 to 0.3 units/kg/day for those with Hemoglobin A1C >8%
      3. Titrate
        1. Increase Basal insulin by 2-4 units or 10-15% once or twice weekly until Blood Glucose controlled
        2. Go to Step 1 when Blood Glucose not at goal despite Basal insulin >0.5 units/kg/day
        3. Hypoglycemia should prompt decrease Insulin 4 units or 10-20% (and address cause)
    2. Other agents to continue
      1. Oral Insulin sensitizer (e.g. Metformin or Glucophage) and
      2. Oral Insulin Secretagogue (e.g. Glipizide)
        1. Stop when Bolus Insulin (e.g. RA) is initiated more than once daily
  3. Step 1: 0-0-RA-G (Basal Plus Protocol)
    1. Indications
      1. Hemoglobin A1C targets not met despite Basal insulin
      2. Basal insulin >0.5 units/kg/day
    2. As an alternative, may use premixed Insulin twice daily (see protocol below)
    3. Add 0.1 units/kg (or 4 units or 10% of basal dose) Bolus Insulin before largest meal
      1. Lispro or Aspart (rapid acting or RA) or
      2. Regular Insulin (if cost is a concern)
        1. Avoid in Stage IV or Stage V significant Chronic Kidney Disease
        2. Avoid if history of severe Hypoglycemia
    4. Other dosing
      1. Decrease Insulin Glargine by 0.1 units/kg if Hemoglobin A1C <8%
      2. Continue Insulin sensitizer (e.g. Metformin)
      3. Caution with Insulin Secretagogue (e.g. Glipizide)
        1. May be continued with caution once per day opposite the rapid acting Insulin dose
        2. Consider discontinuing in the elderly or other risks of Hypoglycemia
    5. Titration
      1. Check Blood GlucoseFasting, before rapid acting (RA) dose and at bedtime
      2. Increase Bolus Insulin by 1-2 units or 10-15% once or twice weekly until Blood Glucose controlled
      3. Hypoglycemia should prompt decrease Insulin 2-4 units or 10-20% (and address cause)
  4. Step 2: RA-0-RA-G (Basal-Bolus Protocol)
    1. Add 0.1 units/kg (or 4 units or 10% of basal dose) rapid acting (RA) Bolus Insulin before 2nd largest meal
    2. Decrease Insulin Glargine by 0.1 units/kg if Hemoglobin A1C <8%
    3. Continue Insulin sensitizer (e.g. Metformin)
    4. Stop Insulin Secretagogue (e.g. Glipizide, Meglitinide)
    5. Check Blood GlucoseFasting, before rapid acting (RA) doses and at bedtime
    6. Hypoglycemia should prompt decrease Insulin 2-4 units or 10-20% (and address cause)
  5. Step 3: RA-RA-RA-G (Basal-Bolus Intensive Protocol)
    1. Add 0.1 units/kg (or 4 units or 10% of basal dose) rapid acting (RA), Bolus Insulin before 3rd largest meal
    2. Decrease Insulin Glargine by 0.1 units/kg if Hemoglobin A1C <8%
    3. Check Blood GlucoseFasting, before rapid acting (RA) doses and at bedtime
    4. Hypoglycemia should prompt decrease Insulin 2-4 units or 10-20% (and address cause)
  6. Precautions
    1. Keep Insulin split into 50% basal and 50% bolus

VIII. Protocol: Starting Basal insulin (e.g. Lantus) and Bolus Insulin (e.g. Lispro)

  1. Step 0: Adjust oral medications
    1. Stop Insulin Secretagogue (Sulfonylurea, Meglitinide) when on twice daily Bolus Insulin
    2. Continue Insulin sensitizers (Metformin, Glitazone)
  2. Step 1: Choose a 24 hour Basal insulin (once daily):
    1. Glargine (Lantus)
    2. Caution with longer acting agents (>24 hours, titrate at >4 day intervals)
      1. Insulin Degludec (Tresiba)
      2. Insulin Glargine U-300 (Toujeo, Toujeo Max Solostar)
  3. Step 2: Choose a Bolus Insulin (pre-meal Insulin):
    1. Regular Insulin (Novolin R, Humulin R)
    2. Glulisine (Apidra)
    3. Lispro (Humalog)
    4. Aspart (Novolog)
  4. Step 3: Starting dose
    1. Hemoglobin A1C <8
      1. Basal insulin 0.1 units/kg once daily AND
      2. Bolus Insulin 0.1 units/kg divided equally before meals (start before breakfast and dinner)
    2. Hemoglobin A1C 8-10
      1. Basal insulin 0.2 units/kg once daily AND
      2. Bolus Insulin 0.2 units/kg divided equally before meals (start before breakfast and dinner)
    3. Hemoglobin A1C >10
      1. Basal insulin 0.3 units/kg once daily AND
      2. Bolus Insulin 0.3 units/kg divided equally before meals (start before breakfast and dinner)

IX. Protocol: Starting Basal/Bolus Insulin using NPH

  1. Background
    1. Other regimens are less complicated and therefore preferred
    2. However, NPH and Regular Insulin are least expensive Insulin options
  2. Step 0: Adjust oral medications
    1. Stop Insulin Secretagogue (Sulfonylurea, Meglitinide) when on twice daily Bolus Insulin
    2. Continue Insulin sensitizers (Metformin, Glitazone)
  3. Step 1: Starting dose
    1. Hemoglobin A1C <8: Total Insulin: 0.1 units/kg in AM and 0.1 units/kg in PM
    2. Hemoglobin A1C 8-10: Total Insulin: 0.2 units/kg in AM and 0.2 units/kg in PM
    3. Hemoglobin A1C >10: Total Insulin: 0.3 units/kg in AM and 0.3 units/kg in PM
  4. Step 2: Divide each Insulin dose into 1/3 bolus (e.g. Regular Insulin) and 2/3 NPH Insulin
  5. Step 3: Schedule 2 doses of Bolus Insulin (e.g. regular) and 2 doses of NPH daily
    1. Breakfast (50%): NPH Insulin (2/3) and Regular Insulin (1/3)
    2. Dinner (50%): NPH Insulin (2/3) and Regular Insulin (1/3)

X. Protocol: Starting Insulin using Premixed Insulin

  1. Step 0: Adjust oral medications
    1. Stop Insulin Secretagogue (Sulfonylurea, Meglitinide)
    2. Continue Insulin sensitizers (Metformin, Glitazone)
  2. Insulin preparations (for twice daily dosing)
    1. Lispro Mix 75/25 or
    2. Aspart Premix 70/30
  3. Starting dose
    1. Based on Insulin Glargine Regimen (Insulin Augmentation) as above
      1. Divide current Basal insulin dose into 2/3 AM and 1/3 PM or
      2. Divide current Basal insulin dose into 1/2 AM and 1/2 PM
    2. Based on current Hemoglobin A1C
      1. A1C <8: 0.1 units/kg in AM and 0.1 units/kg in PM
      2. A1C 8-10: 0.2 units/kg in AM and 0.2 units/kg in PM
      3. A1C >10: 0.3 units/kg in AM and 0.3 units/kg in PM
  4. Titration
    1. Check Blood GlucoseFasting, before Insulin dose and at bedtime
    2. Increase Insulin by 1-2 units or 10-15% once or twice weekly until Blood Glucose controlled
    3. Hypoglycemia should prompt decrease Insulin 2-4 units or 10-20% (and address cause)

XI. Protocol: Converting from Premixed Insulin to Basal Bolus Insulin

  1. Calculate total Insulin units/kg
    1. Total >1.5 units/kg: Lower total to 1.0 unit/kg
    2. Hemoglobin A1C <9: Decrease total Insulin by 10%
  2. Divide total Insulin Dosing
    1. Insulin Glargine: 50% of total Insulin
    2. Rapid acting: 50% of total divided across meals

XII. Protocol: Insulin Adjustments

  1. See Insulin Dosing
  2. See Insulin Adjustment with Carbohydrate Counting
  3. Precautions
    1. Overall, typically maintain basal:Bolus Insulin mix of 50:50 (typical, but lacks evidence)
    2. Indications to add Bolus Insulin
      1. Postprandial Hyperglycemia
      2. Findings of excessive Basal insulin (over-basalization)
        1. Inadequate control despite Basal insulin doses >0.5 units/kg
        2. Fasting Blood Glucose is frequently <70 mg/dl (<3.89 mmol/L)
        3. Bedtime to morning differential >50 mg/dl (2.77 mmol/L)
    3. Findings to readdress Insulin Resistance
      1. Total daily Insulin requirement >2 units/kg
    4. De-intensifying Insulin as Glucose control improves (esp. with addition of GLP1 Agonist, SGLT2 Inhibitor)
      1. Basal insulin may be gradually reduced 10-20%
      2. Bolus Insulin may be gradually reduced 20-50% (esp. as target A1C is approached or surpassed)
  4. Basal insulin (adjusted based on FastinG Blood Sugars from 3 consecutive days)
    1. Adjust units +4: Fasting Glucose >180 mg/dl (>9.99 mmol/L)
    2. Adjust units +2: Fasting Glucose 130-180 mg/dl (7.21 to 9.99 mmol/L)
    3. Adjust units 0: Fasting Glucose 80-129 mg/dl (4.44-7.16 mmol/L)
    4. Adjust units -2: Fasting Glucose 60-79 mg/dl (3.33-4.38 mmol/L)
    5. Adjust units -4: Fasting Glucose <60 mg/dl (<3.33 mmol/L)
      1. Even a single hypoglycemic episode should prompt Insulin adjustment
  5. Rapid-Acting Bolus Insulin (adjusted based on 2 HOUR POST-PRANDIAL, or NEXT PREMEAL Blood Glucose from 3 consecutive days)
    1. Adjust units +2: Fasting Glucose >180 mg/dl (>9.99 mmol/L)
    2. Adjust units +1: Fasting Glucose 130-180 mg/dl (7.21 to 9.99 mmol/L)
    3. Adjust units 0: Fasting Glucose 80-129 mg/dl (4.44-7.16 mmol/L)
    4. Adjust units -2: Fasting Glucose 60-79 mg/dl (3.33-4.38 mmol/L)
    5. Adjust units -4: Fasting Glucose <60 mg/dl (<3.33 mmol/L)
      1. Even a single hypoglycemic episode should prompt Insulin adjustment
  6. Premixed Insulin (adjusted based on FastinG Blood Sugars from 3 consecutive days)
    1. Adjust units +4: Fasting Glucose >180 mg/dl (>9.99 mmol/L)
    2. Adjust units +2: Fasting Glucose 130-180 mg/dl (7.21 to 9.99 mmol/L)
    3. Adjust units 0: Fasting Glucose 80-129 mg/dl (4.44-7.16 mmol/L)
    4. Adjust units -2: Fasting Glucose 60-79 mg/dl (3.33-4.38 mmol/L)
    5. Adjust units -4: Fasting Glucose <60 mg/dl (<3.33 mmol/L)
      1. Even a single hypoglycemic episode should prompt Insulin adjustment
  7. Premixed Insulin (adjusted based on PRE-DINNER Blood Sugars from 3 consecutive days)
    1. Adjust units +4: Fasting Glucose >180 mg/dl (>9.99 mmol/L)
    2. Adjust units +2: Fasting Glucose 130-180 mg/dl (7.21 to 9.99 mmol/L)
    3. Adjust units 0: Fasting Glucose 80-129 mg/dl (4.44-7.16 mmol/L)
    4. Adjust units -2: Fasting Glucose 60-79 mg/dl (3.33-4.38 mmol/L)
    5. Adjust units -4: Fasting Glucose <60 mg/dl (<3.33 mmol/L)
      1. Even a single hypoglycemic episode should prompt Insulin adjustment

XIII. References

  1. Howard-Thompson (2018) Am Fam Physician 97(1):29-37 [PubMed]
  2. Inzucchi (2015) Diabetes Care 38(1): 140-9 [PubMed]
  3. Marrison (2026) Am Fam Physician 113(6): 542-50 [PubMed]

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