Regimen . | Timing and distribution . | Advantages . | Disadvantages . | Adjusting doses . |
---|---|---|---|---|
Regimens that more closely mimic normal insulin secretion | ||||
Insulin pump therapy (hybrid closed-loop, low-glucose suspend, CGM-augmented open-loop, BGM-augmented open-loop) | Basal delivery of URAA or RAA; generally 40–60% of TDD. Mealtime and correction: URAA or RAA by bolus based on ICR and/or ISF and target glucose, with pre-meal insulin ∼15 min before eating. | Can adjust basal rates for varying insulin sensitivity by time of day, for exercise and for sick days. Flexibility in meal timing and content. Pump can deliver insulin in increments of fractions of units. Potential for integration with CGM for low-glucose suspend or hybrid closed-loop. TIR % highest and TBR % lowest with: hybrid closed-loop > low-glucose suspend > CGM-augmented open-loop > BGM-augmented open-loop. | Most expensive regimen. Must continuously wear one or more devices. Risk of rapid development of ketosis or DKA with interruption of insulin delivery. Potential reactions to adhesives and site infections. Most technically complex approach (harder for people with lower numeracy or literacy skills). | Mealtime insulin: if carbohydrate counting is accurate, change ICR if glucose after meal consistently out of target. Correction insulin: adjust ISF and/or target glucose if correction does not consistently bring glucose into range. Basal rates: adjust based on overnight, fasting, or daytime glucose outside of activity of URAA/RAA bolus. |
MDI: LAA + flexible doses of URAA or RAA at meals | LAA once daily (insulin detemir or insulin glargine may require twice-daily dosing); generally 50% of TDD. Mealtime and correction: URAA or RAA based on ICR and/or ISF and target glucose. | Can use pens for all components. Flexibility in meal timing and content. Insulin analogs cause less hypoglycemia than human insulins. | At least four daily injections. Most costly insulins. Smallest increment of insulin is 1 unit (0.5 unit with some pens). LAAs may not cover strong dawn phenomenon (rise in glucose in early morning hours) as well as pump therapy. | Mealtime insulin: if carbohydrate counting is accurate, change ICR if glucose after meal consistently out of target. Correction insulin: adjust ISF and/or target glucose if correction does not consistently bring glucose into range. LAA: based on overnight or fasting glucose or daytime glucose outside of activity time course, or URAA or RAA injections. |
MDI regimens with less flexibility | ||||
Four injections daily with fixed doses of N and RAA | Pre-breakfast: RAA ∼20% of TDD. Pre-lunch: RAA ∼10% of TDD. Pre-dinner: RAA ∼10% of TDD. Bedtime: N ∼50% of TDD. | May be feasible if unable to carbohydrate count. All meals have RAA coverage. N less expensive than LAAs. | Shorter duration RAA may lead to basal deficit during day; may need twice-daily N. Greater risk of nocturnal hypoglycemia with N. Requires relatively consistent mealtimes and carbohydrate intake. | Pre-breakfast RAA: based on BGM after breakfast or before lunch. Pre-lunch RAA: based on BGM after lunch or before dinner. Pre-dinner RAA: based on BGM after dinner or at bedtime. Evening N: based on fasting or overnight BGM. |
Four injections daily with fixed doses of N and R | Pre-breakfast: R ∼20% of TDD. Pre-lunch: R ∼10% of TDD. Pre-dinner: R ∼10% of TDD. Bedtime: N ∼50% of TDD. | May be feasible if unable to carbohydrate count. R can be dosed based on ICR and correction. All meals have R coverage. Least expensive insulins. | Greater risk of nocturnal hypoglycemia with N. Greater risk of delayed post-meal hypoglycemia with R. Requires relatively consistent mealtimes and carbohydrate intake. R must be injected at least 30 min before meal for better effect. | Pre-breakfast R: based on BGM after breakfast or before lunch. Pre-lunch R: based on BGM after lunch or before dinner. Pre-dinner R: based on BGM after dinner or at bedtime. Evening N: based on fasting or overnight BGM. |
Regimens with fewer daily injections | ||||
Three injections daily: N+R or N+RAA | Pre-breakfast: ∼40% N + ∼15% R or RAA. Pre-dinner: ∼15% R or RAA. Bedtime: 30% N. | Morning insulins can be mixed in one syringe. May be appropriate for those who cannot take injections in middle of day. Morning N covers lunch to some extent. Same advantages of RAAs over R. Least (N + R) or less expensive insulins than MDI with analogs. | Greater risk of nocturnal hypoglycemia with N than LAAs. Greater risk of delayed post-meal hypoglycemia with R than RAAs. Requires relatively consistent mealtimes and carbohydrate intake. Coverage of post-lunch glucose often suboptimal. R must be injected at least 30 min before meal for better effect. | Morning N: based on pre-dinner BGM. Morning R: based on pre-lunch BGM. Morning RAA: based on post-breakfast or pre-lunch BGM. Pre-dinner R: based on bedtime BGM. Pre-dinner RAA: based on post-dinner or bedtime BGM. Evening N: based on fasting BGM. |
Twice-daily “split-mixed”: N+R or N+RAA | Pre-breakfast: ∼40% N + ∼15% R or RAA. Pre-dinner: ∼30% N + ∼15% R or RAA. | Least number of injections for people with strong preference for this. Insulins can be mixed in one syringe. Least (N+R) or less (N+RAA) expensive insulins vs analogs. Eliminates need for doses during the day. | Risk of hypoglycemia in afternoon or middle of night from N. Fixed mealtimes and meal content. Coverage of post-lunch glucose often suboptimal. Difficult to reach targets for blood glucose without hypoglycemia. | Morning N: based on pre-dinner BGM. Morning R: based on pre-lunch BGM. Morning RAA: based on post-breakfast or pre-lunch BGM. Evening R: based on bedtime BGM. Evening RAA: based on post-dinner or bedtime BGM. Evening N: based on fasting BGM. |
Regimen . | Timing and distribution . | Advantages . | Disadvantages . | Adjusting doses . |
---|---|---|---|---|
Regimens that more closely mimic normal insulin secretion | ||||
Insulin pump therapy (hybrid closed-loop, low-glucose suspend, CGM-augmented open-loop, BGM-augmented open-loop) | Basal delivery of URAA or RAA; generally 40–60% of TDD. Mealtime and correction: URAA or RAA by bolus based on ICR and/or ISF and target glucose, with pre-meal insulin ∼15 min before eating. | Can adjust basal rates for varying insulin sensitivity by time of day, for exercise and for sick days. Flexibility in meal timing and content. Pump can deliver insulin in increments of fractions of units. Potential for integration with CGM for low-glucose suspend or hybrid closed-loop. TIR % highest and TBR % lowest with: hybrid closed-loop > low-glucose suspend > CGM-augmented open-loop > BGM-augmented open-loop. | Most expensive regimen. Must continuously wear one or more devices. Risk of rapid development of ketosis or DKA with interruption of insulin delivery. Potential reactions to adhesives and site infections. Most technically complex approach (harder for people with lower numeracy or literacy skills). | Mealtime insulin: if carbohydrate counting is accurate, change ICR if glucose after meal consistently out of target. Correction insulin: adjust ISF and/or target glucose if correction does not consistently bring glucose into range. Basal rates: adjust based on overnight, fasting, or daytime glucose outside of activity of URAA/RAA bolus. |
MDI: LAA + flexible doses of URAA or RAA at meals | LAA once daily (insulin detemir or insulin glargine may require twice-daily dosing); generally 50% of TDD. Mealtime and correction: URAA or RAA based on ICR and/or ISF and target glucose. | Can use pens for all components. Flexibility in meal timing and content. Insulin analogs cause less hypoglycemia than human insulins. | At least four daily injections. Most costly insulins. Smallest increment of insulin is 1 unit (0.5 unit with some pens). LAAs may not cover strong dawn phenomenon (rise in glucose in early morning hours) as well as pump therapy. | Mealtime insulin: if carbohydrate counting is accurate, change ICR if glucose after meal consistently out of target. Correction insulin: adjust ISF and/or target glucose if correction does not consistently bring glucose into range. LAA: based on overnight or fasting glucose or daytime glucose outside of activity time course, or URAA or RAA injections. |
MDI regimens with less flexibility | ||||
Four injections daily with fixed doses of N and RAA | Pre-breakfast: RAA ∼20% of TDD. Pre-lunch: RAA ∼10% of TDD. Pre-dinner: RAA ∼10% of TDD. Bedtime: N ∼50% of TDD. | May be feasible if unable to carbohydrate count. All meals have RAA coverage. N less expensive than LAAs. | Shorter duration RAA may lead to basal deficit during day; may need twice-daily N. Greater risk of nocturnal hypoglycemia with N. Requires relatively consistent mealtimes and carbohydrate intake. | Pre-breakfast RAA: based on BGM after breakfast or before lunch. Pre-lunch RAA: based on BGM after lunch or before dinner. Pre-dinner RAA: based on BGM after dinner or at bedtime. Evening N: based on fasting or overnight BGM. |
Four injections daily with fixed doses of N and R | Pre-breakfast: R ∼20% of TDD. Pre-lunch: R ∼10% of TDD. Pre-dinner: R ∼10% of TDD. Bedtime: N ∼50% of TDD. | May be feasible if unable to carbohydrate count. R can be dosed based on ICR and correction. All meals have R coverage. Least expensive insulins. | Greater risk of nocturnal hypoglycemia with N. Greater risk of delayed post-meal hypoglycemia with R. Requires relatively consistent mealtimes and carbohydrate intake. R must be injected at least 30 min before meal for better effect. | Pre-breakfast R: based on BGM after breakfast or before lunch. Pre-lunch R: based on BGM after lunch or before dinner. Pre-dinner R: based on BGM after dinner or at bedtime. Evening N: based on fasting or overnight BGM. |
Regimens with fewer daily injections | ||||
Three injections daily: N+R or N+RAA | Pre-breakfast: ∼40% N + ∼15% R or RAA. Pre-dinner: ∼15% R or RAA. Bedtime: 30% N. | Morning insulins can be mixed in one syringe. May be appropriate for those who cannot take injections in middle of day. Morning N covers lunch to some extent. Same advantages of RAAs over R. Least (N + R) or less expensive insulins than MDI with analogs. | Greater risk of nocturnal hypoglycemia with N than LAAs. Greater risk of delayed post-meal hypoglycemia with R than RAAs. Requires relatively consistent mealtimes and carbohydrate intake. Coverage of post-lunch glucose often suboptimal. R must be injected at least 30 min before meal for better effect. | Morning N: based on pre-dinner BGM. Morning R: based on pre-lunch BGM. Morning RAA: based on post-breakfast or pre-lunch BGM. Pre-dinner R: based on bedtime BGM. Pre-dinner RAA: based on post-dinner or bedtime BGM. Evening N: based on fasting BGM. |
Twice-daily “split-mixed”: N+R or N+RAA | Pre-breakfast: ∼40% N + ∼15% R or RAA. Pre-dinner: ∼30% N + ∼15% R or RAA. | Least number of injections for people with strong preference for this. Insulins can be mixed in one syringe. Least (N+R) or less (N+RAA) expensive insulins vs analogs. Eliminates need for doses during the day. | Risk of hypoglycemia in afternoon or middle of night from N. Fixed mealtimes and meal content. Coverage of post-lunch glucose often suboptimal. Difficult to reach targets for blood glucose without hypoglycemia. | Morning N: based on pre-dinner BGM. Morning R: based on pre-lunch BGM. Morning RAA: based on post-breakfast or pre-lunch BGM. Evening R: based on bedtime BGM. Evening RAA: based on post-dinner or bedtime BGM. Evening N: based on fasting BGM. |
BGM, blood glucose monitoring; CGM, continuous glucose monitoring; ICR, insulin:carbohydrate ratio; ISF, insulin sensitivity factor; LAA, long-acting analog; MDI, multiple daily injections; N, NPH insulin; R, short-acting (regular) insulin; RAA, rapid-acting analog; TDD, total daily insulin dose; URAA, ultra-rapid-acting analog. Reprinted from Holt et al. (5).