Introduction
Premixed Insulin: Formulations and Pharmacokinetics
Type of premixed insulin | Low-mix formulations | Mid-mix formulations | High-mix formulations |
---|---|---|---|
Premixed regular insulin-NPH | 30% insulin regular/70% insulin NPH | 50% insulin regular/50% insulin NPH | Biphasic human insulin 75 75% insulin regular/25% insulin NPH |
Premixed insulin analogs | 30% insulin aspart/70% insulin aspart protamine 25% insulin lispro/75% insulin lispro protamine | 50% insulin lispro/50% insulin lispro protamine 50% insulin aspart/50% insulin aspart protamine | Biphasic human lispro 75 Biphasic human lispro 70 Biphasic human aspart 70 |
Coformulation | 70% insulin degludec/30% insulin aspart |
Premixed Insulin: Initiation and Intensification
Factors Influencing Choice of Premixed Formulations
Patient-Centered/Subjective Factors
Parameters | Comments |
---|---|
Duration of diabetes Duration of uncontrolled hyperglycemia | Longer duration of diabetes and uncontrolled hyperglycemia requires both basal and prandial coverage with exogenous insulin |
Symptoms of hyperglycemia | Persons with symptomatic diabetes (polyuria, polydipsia, polyphagia, weight loss, frequent infection) require both basal and prandial coverage |
Associated acute comorbidity | Examples: non-healing ulcers, refractory or recurrent infections, slow-healing infections, e.g., tuberculosis or slow-healing trauma, e.g., fractures, preoperative uncontrolled hyperglycemia |
Lifestyle | Meal pattern (number of meals or snacks per day), relative quantity of meals, their composition (proportion of carbohydrates, glycemic index), and regularity |
Drug therapy | Inadequacy of multiple drugs that target postprandial glycemia, e.g., sulfonylureas and alpha glucosidase inhibitors, suggests the need for prandial insulin coverage. Inadequacy of drugs that target both fasting and postprandial glycemia, e.g., DPP4i GLP1RA and SGLT2i, also suggests the need for both basal and prandial insulin. Inadequacy of basal insulin must be managed by addition of prandial insulin, separately or as part of a dual-action insulin. Inadequacy of once-daily premixed insulin suggests the need for twice-daily or more frequent insulin administration |
Glycemic status | Patterns of glycemia, risk of hypoglycemia, and magnitude of glycemic variability Glucometric indices: postprandial glucose excursions (PPGE) and prandial fasting index (PFI) |
Patient preference | Willingness/ability to handle Number of injections Number of delivery devices Frequency of monitoring |
Dietary Factors
Lifestyle
Overall Health Status
Metabolic Health
Number of Injections/Day
Patient Preferences
Patient Satisfaction and Convenience
Insulin Distress
Laws of Parsimony
Gluco-Centric/Objective Parameters
Glycemic Status
Glycemic Variations
Glucometric Indices
Indices | Prefer premixa | Prefer basala |
---|---|---|
PPGE = PPG − FPG | 40–74 mg/dl | < 40 mg/dl |
2.2–4.1 mmol/l | < 2.2 mmol/l | |
\({\text{PFI}}\; = \;\frac{{{\text{PPG}}\; - \;{\text{FPG}}}}{\text{FPG}}\)
| 0.4–0.6 | < 0.4 |
FPG/HbA1cb | ≤ 20 | ≥ 20 |
Summary
Current therapy | Current medical status | Current glycemic status | Dietary pattern | Intervention |
---|---|---|---|---|
Monotherapy OAD | Symptoms of hyperglycemia/catabolism/asthenia Acute medical or surgical comorbidity requiring timely resolution of hyperglycemia | Inadequate fasting + postprandial control | Regular meals | Initiation with premixed insulin, preferably twice daily |
OAD, dual or triple combination | Symptoms of hyperglycemia/catabolism/asthenia Acute medical or surgical comorbidity requiring timely resolution of hyperglycemia Asymptomatic persons | Inadequate fasting + postprandial control | One heavy meal | Initiation with premixed insulin once daily |
Two heavy meals | Initiation with premixed insulin twice daily | |||
Basal insulin + OADs | Symptoms of hyperglycemia/catabolism/asthenia Acute medical or surgical comorbidity requiring timely resolution of hyperglycemia Asymptomatic persons | High HbA1c inspite of adequate FPG control High PPG, unacceptable nocturnal hypoglycemia | One heavy meal | Intensification to premixed insulin once daily |
Two heavy meals | Intensification to premixed insulin twice daily | |||
Premixed insulin once daily + OADs | Symptoms of hyperglycemia/catabolism/asthenia Acute medical or surgical comorbidity requiring timely resolution of hyperglycemia Asymptomatic persons | High HbA1c inspite of adequate FPG control High PPG, unacceptable nocturnal hypoglycemia | Heavy meals | Intensification to premixed insulin twice daily |
Premixed insulin twice daily + OADs | Symptoms of hyperglycemia/catabolism/asthenia Acute medical or surgical comorbidity requiring timely resolution of hyperglycemia Asymptomatic persons | High HbA1c despite adequate FPG control | Heavy meals | Intensification to high mix insulin |
High PPG, unacceptable nocturnal hypoglycemia | Heteromix insulina | |||
Post-lunch hyperglycemia | Three heavy meals | Intensification to premixed insulin thrice daily |