Insulin Regimens

Basic Insulin Regimens

For patients with type 2 diabetes starting insulin, basal insulin alone is usually recommended first, along with continuing 1-2 oral agents (see figure above). If the A1C is >9%, or patients are motivated to do more than one injection per day, a patient could be initiated from the start on twice daily pre-mixed insulin, or basal + mealtime short-acting insulin with the largest meal of the day. If basal insulin is titrated to the maximum dose possible without causing hypoglycemia, but the A1C remains above goal, patients can consider using rapid-acting mealtime insulin, initially for the largest meal, and then for more meals later as needed (“advanced insulin therapy,” see below).  Once a patient is using bolus insulin, sulfonylureas are generally withdrawn to avoid hypoglycemia.

Once an insulin strategy is initiated, titration of the insulin dose is important, with dose adjustments made based on the prevailing glucose levels as reported by the patient.  Comprehensive education regarding self-monitoring of blood glucose, diet, exercise, and the avoidance of, and response to, hypoglycemia are critical in any patient on insulin therapy.

Basic Insulin Regimens
CANDIDATES – Use for patients with 2 or more of the following: Consistent schedule Regular mealtimes <10 hours between breakfast and dinner For those unable to mix or measure insulin, see premix
Regimen	Comments	AM	PM	Bedtime
GLARGINE OR DETEMIR WITH ORAL AGENTS	Use for type 2 DM with high fasting glucoseUse AM fasting glucose to titrate insulin	ORAL AGENTS	ORAL AGENTS	GLARGINE DETEMIR
NPH WITH ORAL AGENTS	Use for type 2 DM with high fasting glucoseUse AM fasting glucose to titrate insulin	ORAL AGENTS	ORAL AGENTS	NPH
RAPID ACTING + NPH	Use for pts who choose NOT to snack; consider when post-meal hyperglycemia is present; when fasting glucose is at goal on basal insulin but A1C is above goal	RANPH	RA	NPH
GLARGINE OR DETEMIR + RAPID ACTING	Use for patients who choose NOT to snack; consider when post-meal hyperglycemia is present after largest meal; when fasting glucose is at goal on basal insulin but A1C is above goal		RA timing depends on patient’s need (often lunch or dinner)	GLARGINE DETEMIR
RAPID ACTING + NPH PREMIX PEN	Use premixed pen as easier way to start insulin or if unable to measure / mix; Use for patients who choose NOT to snack; consider when post-meal hyperglycemia is present	RA             RA NPH           NPH (Pen)         (Pen)		–
NPH + REGULAR PREMIX PEN	Use premixed pen as easier way to start insulin or if unable to measure / mix; Use for patients who choose TO snack;consider when post-meal hyperglycemia is present	Regular      Regular NPH            NPH (Pen)          (Pen)
Adapted from AAFP and ADA recommendations

Dosing and Adjustments:

For single night-time dose of glargine, the initial dose is 0.1 – 0.2 U / kg / day (although larger starting doses may be reasonable for severely hyperglycemic patients). The manufacturer recommends an initial dose of 10 U. When working with basal insulin, the fasting glucose is the target to work with. A reasonable initial target for many patients is a morning fasting glucose of <140 mg/dL. The dose can be increased by 1–2 units (or by 5-10% increments for those already on higher doses) every 4 – 7 days until the morning fasting glucose has reached target. Ideally, patients can be taught to adjust their dose according to their readings.

Insulin dosage should always be adjusted for hypoglycemia first. Downward titration of insulin dosing should be performed if the patient has any low glucose values.

Premixed insulin with NPH and a rapid acting component is more expensive but provides better post-meal glucose control. The usual starting dose is 0.3 – 0.5 U / kg / day, generally increasing to 0.7 – 1.2 U / kg / day.

Once a patient is using basal insulin in the 0.5 to 1 U/Kg/day range, it is likely that prandial insulin will also be required to achieve adequate A1C control.

Advanced Insulin Therapy

The patient may become comfortable with a basic insulin regimen and using familiar daily doses. Unfortunately, most individuals require more aggressive therapy over time. Basic regimens are inflexible and can increase the risk of hypoglycemia. Advanced regimens are more flexible for a patient’s life demands (e.g. exercise regimen changes, work schedule demands, meal intake variability). Advanced regimens require both an increased frequency of insulin administration and self-monitored glucose levels. Patient education is critical and they must understand the effects of insulin, carbohydrate intake, insulin injection administration, and exercise. Most advanced regimens use rapid acting insulin and long acting insulin. The following recommendation is also based on the ADA and AAFP:

Advanced Insulin Regimens
Regimen	AM	Noon	PM	Bedtime
RAPID ACTING + NPH	RA NPH	RA only	RA NPH
RAPID ACTING + GLARGINE or DETEMIR	RA	RA	RA	GLARGINE or DETEMIR
Regular insulin can be substituted for patients who snack without bolus coverage or if there is a cost issue for patients.

The initial total insulin dosage for advanced insulin therapy is on the order of 0.4 to 0.5 U / kg / day for a patient naïve to insulin. Many patients will require more over time on the order of 1 – 2 U / kg / day. Typically half of the total will go to the bolus dose and half to the basal dose.

Alternate Insulin Administration and Glucose Monitoring Methods

Insulin pumps may be useful for some patients as they deliver rapid acting insulin on a continuous basis as a basal dose. The patient then pushes a button to deliver bolus doses with meals. These patients are still required to use fingersticks to monitor their glucose.

Continuous glucose monitoring (CGM) is available for some patients, although the method of data reporting and analysis has not yet been thoroughly standardized. It also is expensive, out of reach for many patients financially, and is associated with a modest drop in A1C.  The ASPIRE trial showed that an insulin pump combined with CGM was successful for 247 patients over 16 years old. However, a true ‘artificial pancreas’ remains an experimental hope at this time; CMG requires additional standardization and adaptation (Bergenstal, 2013).

Side Effects of Injected Insulin

Lipodystrophy can happen at sites of injection, with lipohypertrophy occurring more often in men and lipoatrophy occurring more commonly in women. Changing injection sites can prevent this side effect.

Local skin reactions such as itching, redness, and discomfort may occur. Most reactions resolve with desensitization over 6 weeks. Antihistamines can be used in the interim.

Systemic reactions are rare but allergies can develop. They can vary from urticaria to anaphylaxis. It is more common in patients with penicillin allergies or atopic dermatitis. It also occurs more frequently in those patients using insulin intermittently. Desensitization therapy is now available.

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