Can a patient with type 2 diabetes (T2D) taking metformin, vildagliptin (galvus), and regular insulin, who requires 40 units of glargine, receive it in divided doses twice daily?

Can Glargine 40 Units Be Given Twice Daily in Divided Doses?

Yes, insulin glargine can be given twice daily in divided doses when once-daily administration fails to provide adequate 24-hour coverage, though this is not the standard initial approach. 1

When to Consider Twice-Daily Glargine Dosing

The 2022 ADA Standards explicitly recognize that insulin glargine may require twice-daily dosing when once-daily administration fails to provide 24-hour coverage, particularly in specific clinical situations 1:

• Inadequate 24-hour coverage with once-daily dosing (persistent hyperglycemia before the next dose)
• Persistent nocturnal hypoglycemia with morning hyperglycemia (suggesting insulin wearing off)
• Type 1 diabetes with high glycemic variability despite optimal once-daily titration 1

A case report demonstrated successful resolution of morning hypoglycemia by switching from once-daily to twice-daily glargine when dose titration and timing changes failed 2. This approach has precedent from prior studies using multiple daily injections with NPH and Ultralente insulins 2.

Critical Threshold Consideration First

Before splitting glargine to twice daily, verify that the total daily dose exceeds 0.5 units/kg/day. If the 40-unit dose approaches or exceeds this threshold (0.5 units/kg/day), adding prandial insulin or a GLP-1 receptor agonist is more appropriate than manipulating the basal insulin regimen 1, 3. For a patient requiring 40 units, this threshold is reached at approximately 80 kg (176 lbs) body weight.

Clinical signals indicating you should add prandial coverage rather than split basal insulin include 1:

• Basal dose >0.5 units/kg/day
• Bedtime-to-morning glucose differential ≥50 mg/dL
• Episodes of hypoglycemia
• High glucose variability throughout the day

Practical Approach to Splitting the Dose

If twice-daily dosing is warranted based on inadequate 24-hour coverage (not overbasalization), divide the total daily dose approximately 50:50 between morning and evening injections 1. For 40 units total:

• Morning dose: 20 units
• Evening dose: 20 units

Alternatively, you can adjust the split based on glucose patterns—if morning hyperglycemia predominates, weight the evening dose slightly higher; if afternoon/evening hyperglycemia is the issue, weight the morning dose higher 1.

Important Caveats and Monitoring

Once-daily dosing remains the standard initial approach for glargine, with twice-daily dosing reserved for patients who fail to achieve targets or experience problematic hypoglycemia with optimized once-daily regimens 1. Before implementing twice-daily glargine:

1. Ensure proper once-daily dose titration has been attempted at different times of day (morning vs. evening) 1
2. Consider whether switching to newer ultra-long-acting insulins (degludec U-100 or U-200, or glargine U-300) might provide more stable 24-hour coverage 1
3. For type 2 diabetes patients requiring intensification beyond basal insulin, adding GLP-1 receptor agonists or prandial insulin may be more appropriate than splitting basal insulin 1, 4

Monitor fasting glucose daily and pre-dinner glucose to independently titrate morning and evening doses 1. This allows addressing specific patterns of hyperglycemia or hypoglycemia that differ between the two time periods 1.

Context for This Patient

Given this patient is on metformin, vildagliptin (DPP-4 inhibitor), and regular insulin, the regimen suggests type 2 diabetes with some prandial coverage already in place. Before splitting the glargine:

• Verify the patient's weight to determine if 40 units exceeds 0.5 units/kg/day
• Assess glucose patterns throughout the day—if postprandial hyperglycemia is the primary issue, intensifying prandial coverage is more appropriate than splitting basal insulin 1, 4
• Consider discontinuing vildagliptin if advancing to more intensive insulin therapy, as DPP-4 inhibitors provide modest benefit when multiple insulin doses are used 5
• Continue metformin unless contraindicated, as it reduces insulin requirements and provides complementary glucose-lowering effects 1, 5

The combination of basal insulin plus GLP-1 receptor agonist provides superior outcomes compared to basal-bolus insulin regimens with less hypoglycemia and weight gain 1, 5. If the patient is not already on a GLP-1 RA, this should be strongly considered before splitting glargine doses 1.