What is the recommended approach for initiating insulin therapy?

How to Start Insulin Therapy

Begin basal insulin at 10 units once daily or 0.1-0.2 units/kg/day for insulin-naïve patients with type 2 diabetes, administered subcutaneously at the same time each day, and titrate by 2-4 units every 3-7 days until fasting glucose reaches 80-130 mg/dL. 1, 2

Initial Insulin Selection and Dosing

Choose Basal Insulin as First-Line

• Basal insulin (glargine, detemir, degludec, or NPH) is the most practical initial regimen for patients starting insulin therapy 1
• Long-acting basal analogs provide greater stability and flexibility than older preparations, with lower nocturnal hypoglycemia risk compared to NPH insulin 3, 4
• Administer subcutaneously into the abdominal area, thigh, or deltoid once daily at any time of day, but at the same time every day 2

Starting Dose Calculation

• For type 2 diabetes patients not currently on insulin: 0.2 units/kg/day or up to 10 units once daily 2
• For a 70 kg patient, this translates to 7-14 units per day 1
• For elderly patients or those with renal insufficiency: use the lower end (0.1 units/kg/day) to minimize hypoglycemia risk 1
• For type 1 diabetes: approximately one-third of total daily insulin requirements, with short-acting insulin covering the remainder 2

Maintain Concurrent Medications

• Continue metformin when initiating basal insulin, as it provides complementary glucose-lowering and reduces total insulin requirements 3
• Consider maintaining SGLT2 inhibitors for their cardiovascular benefits and insulin-sparing effects 3, 1
• Typically wean or discontinue sulfonylureas and DPP-4 inhibitors when starting insulin 3

Titration Protocol

Standard Titration Approach

• Increase basal insulin by 2-4 units every 3-7 days until fasting blood glucose consistently reaches target of 80-130 mg/dL 1, 4
• Base adjustments on the mean of 3 consecutive fasting glucose measurements 5
• A simpler alternative: increase by 1 unit per day for NPH, detemir, and glargine 100 units/mL 4

Patient Self-Titration Algorithm

• Equip patients with a self-titration algorithm based on self-monitoring of blood glucose, which improves glycemic control 3, 1
• Example patient-managed protocol: increase insulin dose by 2 units every 3 days in the absence of blood glucose <72 mg/dL 5
• Patient-managed titration achieves greater HbA1c reductions (-1.22% vs -1.08%) compared to clinic-managed approaches 5

Hypoglycemia Management During Titration

• If hypoglycemia occurs, determine the cause; if no clear reason is found, reduce the dose by 10-20% 1
• Hold titration if fasting glucose <72 mg/dL (<4.0 mmol/L) 5
• Increase frequency of blood glucose monitoring during insulin initiation and dose changes 2

When to Intensify Beyond Basal Insulin

Indications for Combination Injectable Therapy

• If basal insulin has been titrated to acceptable fasting glucose (or dose >0.5 units/kg/day) and A1C remains above goal, advance to combination injectable therapy 3
• Consider adding a GLP-1 receptor agonist to basal insulin, which provides potent glucose-lowering with less weight gain and hypoglycemia compared to intensified insulin regimens 3
• Two fixed-ratio combination products are available: insulin glargine plus lixisenatide (iGlarLixi) and insulin degludec plus liraglutide (IDegLira) 3

Adding Prandial Insulin

• Start with a single prandial dose of rapid-acting insulin (4 units or 10% of basal dose) with the largest meal 1, 6
• Advance to multiple prandial doses if necessary 3
• When adding prandial insulin, consider reducing basal insulin by 4 units or 10% if A1C <8% 6
• Increase prandial insulin by 1-2 units or 10-15% twice weekly based on 2-hour postprandial glucose readings 1, 6

Alternative: Premixed Insulin

• Converting to two doses of premixed insulin is a simple, convenient alternative for patients who cannot manage multiple daily injections 3
• Premixed insulin offers less flexibility but may improve adherence in select patients 6

Critical Safety Considerations

Injection Site Management

• Rotate injection sites within the same region to reduce risk of lipodystrophy and localized cutaneous amyloidosis 2
• Do not inject into areas of lipodystrophy or localized cutaneous amyloidosis, as this causes hyperglycemia 2
• Patients who have repeatedly injected into affected areas should change to unaffected areas and closely monitor for hypoglycemia 2

Administration Precautions

• Never share insulin pens, syringes, or needles between patients due to blood-borne pathogen transmission risk 2
• Do not administer intravenously or via an insulin pump 2
• Do not dilute or mix basal insulin with any other insulin or solution 2
• Visually inspect for particulate matter and discoloration; only use if clear and colorless 2

Avoiding Overbasalization

• Do not continue escalating basal insulin dose beyond approximately 0.5-1.0 units/kg/day without meaningful fasting glucose reduction 1, 4
• Signs of overbasalization include: elevated glucose differential between bedtime and morning, hypoglycemia, or high glucose variability 1
• When overbasalization occurs, re-evaluate therapy and consider adding prandial insulin or GLP-1 receptor agonist rather than further increasing basal insulin 1, 4

Special Clinical Situations

Switching from Other Insulins

• From once-daily NPH to glargine: use the same dose 2
• From twice-daily NPH to once-daily glargine: use 80% of total NPH dose 2
• From TOUJEO (insulin glargine 300 units/mL) to glargine 100 units/mL: use 80% of TOUJEO dose 2
• Closely monitor glucose when switching and during initial weeks thereafter 2

Corticosteroid-Induced Hyperglycemia

• Consider administering NPH insulin in the morning to counteract steroid-induced daytime hyperglycemia 1
• Patients on glucocorticoids may require higher insulin doses due to steroid-induced insulin resistance 6

Acute Hyperglycemia (DKA/HHS)

• For mild DKA, subcutaneous regular insulin every 4 hours is effective 3
• Unless DKA is mild, regular insulin by continuous intravenous infusion is preferred 3
• Criteria for DKA resolution: glucose <200 mg/dL, bicarbonate ≥18 mEq/L, venous pH >7.3 3
• When transitioning from IV to subcutaneous insulin, continue IV insulin for 1-2 hours after subcutaneous dose to ensure adequate plasma insulin levels 3

Patient Education Essentials

Comprehensive Self-Management Training

• Provide instruction on self-monitoring of blood glucose, insulin injection technique, and hypoglycemia recognition and treatment 3, 1, 6
• Supply patients with written instructions for insulin dose adjustments based on glucose patterns 6
• Ensure patients have hypoglycemia treatment supplies 6
• Educate patients that insulin initiation reflects disease progression, not personal failure 3

Monitoring Requirements

• Self-monitoring of blood glucose at least four times daily is essential for meticulous control 7
• Increase monitoring frequency during insulin initiation, dose changes, illness, or changes in physical activity 2
• Reassess glycemic control every 2-3 months with monitoring for hypoglycemia and weight changes 6