What to do after basal insulin: 3 Tx strategies for type 2 diabetes

GLP-1RAs can be considered as an add-on therapy for patients whose HbA1c exceeds 7% and whose fasting blood glucose ranges from 80 to 130 mg/dL, or for patients with a basal insulin dose >0.5 unit/kg/d. The 5 currently available GLP-1RAs (exenatide, exenatide extended-release, liraglutide, albiglutide, and dulaglutide) are compared in TABLE 2.^11-15

Dosing varies with each agent and includes twice daily before meals for exenatide, once daily (independent of meals) for liraglutide, and once weekly for exenatide extended-release, albiglutide, and dulaglutide. These agents should not be used for patients with a history of pancreatitis or a personal or family history of medullary thyroid cancer or multiple endocrine neoplasia type 2. Because exenatide is cleared through the kidneys, its use is contraindicated in patients with a creatinine clearance <30 mL/min or end-stage renal disease. Caution is advised for its use in patients with a creatinine clearance of 30 to 50 mL/min.¹¹

Basal plus one strategy

To best utilize prandial insulin, it is important to know what the patient’s glucose readings are before and after meals as assessed by the 7-point or staggered blood glucose monitoring techniques described earlier. Once you have clarified which meal(s) are raising the patient’s glucose levels, selecting appropriate treatment becomes easier. To reduce the glucose-monitoring burden for the patient, it may be acceptable to allow the patient to omit the fasting glucose measurement (if stable).

The first major decision is whether to treat one meal per day (basal plus one) or all meals (basal-bolus). Adding a rapid-acting insulin prior to one meal a day (usually the largest meal) is a reasonable starting point.¹⁶

The meal that produces the highest postprandial glucose readings can be considered the meal of greatest glycemic impact. The “delta” value—the difference between pre-meal glucose and 2-hour postprandial glucose readings—also helps to determine the largest meal of the day.¹⁷ The average physiologic delta is ≤50 mg/dL.¹⁷ If the delta for a meal is >75 mg/dL, consider initiating prandial insulin prior to that meal and titrating the dose to achieve a target glucose level of <130 mg/dL before the next meal.

A GLP-1RA can be considered for patients with an HbA1c >7% and a fasting glucose ranging from 80 to 130 mg/dL.

Using 4 to 6 units of a rapid-acting insulin per meal is a good initial regimen for a basal plus one (as well as for a basal-bolus) approach.¹⁶ If the patient experiences significantly increased insulin demands as indicated by glucose patterns where the post-meal glucose is still consistently above 180 mg/dL, the initial regimen may be modified to 0.1 unit per kg per meal,^17-19 and then titrated up to a maximum of 50% of the total daily insulin dose (TDD) for basal plus one¹⁶ (or 10%-20% of TDD per meal for basal-bolus).

Consider the timing of administration. Rapid-acting insulin analogs exhibit peak pharmacodynamic activity 60 minutes after injection (TABLE 3).²⁰

Peak carbohydrate absorption following a meal occurs approximately 75 to 90 minutes after eating begins.^17,21 Thus, to synchronize the action of insulin with carbohydrate digestion, the analog should be injected 15 minutes before meals. This can be increased by titrating prandial insulin by 1 unit/d to a goal of either a 90-minute to 2-hour postprandial glucose of <140 to 180 mg/dL or the next preprandial glucose of <130 mg/dL.¹⁶ The goal is to obtain a near-normal physiologic delta of <50 mg/dL. The drop in delta noted with every unit of insulin added to the current dose can provide a rough approximation of how many additional insulin titrations will be needed to achieve a delta of <50 mg/dL.

Basal-bolus combination

A gradual increase from one injection before a single meal each day to as-needed multiple daily injections (MDIs) is the next step in hyperglycemia management. Starting slow and building up to insulin therapy prior to each meal offers structure, simplicity, and physician-patient confidence in diabetes management. The slow progression from basal plus one to basal-bolus combination allows the patient ease into a complex, labor-intensive regimen of MDIs. Additionally, the stepwise reduction of postprandial hyperglycemia with this slow approach often reduces the incidence of hypoglycemia (more on this in a moment).⁸

Advanced insulin users can calculate an “insulin-to-carbohydrate ratio” (ICR) to estimate the amount of insulin they need to accommodate the amount of carbohydrates they ingest per meal. An ICR of 1:10 implies that the patient administers 1 unit of insulin for every 10 grams of carbohydrates ingested. For example, if a patient with an ICR of 1:10 concludes that his meal contains a total of 60 grams of carbohydrates, then he would administer 6 units of insulin prior to this meal to address the anticipated post-meal hyperglycemia.