When and How to Use Various Types of Insulins

Educational Objectives

The goal of this program is to improve prescription of insulin. After hearing and assimilating this program, the clinician will be better able to:

1. Adjust dosing of noninsulin medications to prevent hypoglycemia following initiation of insulin administration.
2. Prevent adverse effects from various types of insulin.

Summary

Insulin: all individuals with type 1 diabetes mellitus (T1DM) need insulin; ≈405 million people worldwide (29 million people in the United States) have type 2 diabetes mellitus (T2DM); insulin use varies by, eg, patient access, glycemic target; insulin is a relatively precise instrument and one of the safer treatments, even though hypoglycemia is a risk; however, insulin-related issues are among the most common reasons for people to visit emergency departments; insulin is associated with weight gain; insulin can be complicated to initiate and adjust without help from office personnel; very expensive; reassure and address fears that people have; participants taking insulin in the United Kingdom Prospective Diabetes Study (King et al, 1999) gained (≈9 lb in the first 3 yr; discuss ways to mitigate weight gain (through, eg, lifestyle changes); try to limit dosing as much as possible to avoid hypoglycemia; use insulin in conjunction with medications that aid in weight loss

When to start insulin: a patient-centered decision; consider risks for side effects, issues with cost and access, and social determinants of health; consider early introduction of insulin if patients continue to lose weight because of hyperglycemia, have symptoms of hyperglycemia, have glycated hemoglobin A_1C (HbA_1C) >10% or blood glucose consistently >300 mg/dL, or if patients do not maintain goals; most often, insurance influences the type of insulin which is chosen

Method of administration: insulin should be injected into the subcutaneous tissue, as intramuscular injection can lead to unpredictable absorption; some studies suggest that shorter needles are as effective as longer needles in adults with obesity; it is important to rotate the site of administration to avoid lipohypertrophy which can hinder absorption of insulin; demonstrate insulin administration to patients; patients should see a certified diabetes care and education specialist

Noninsulin medications: the primary goal when initiating insulin is to avoid hypoglycemia; eg, metformin, dipeptidyl peptidase-4 (DPP-4) inhibitors are unlikely to be associated with hypoglycemia, while patients taking, eg, sulfonylureas may require closer follow-up, especially patients with liver disease and chronic kidney disease; eg, GLP inhibitors, SGLT2 inhibitors, acarbose may not require dose adjustment though may limit total insulin dosing; thiazolidinediones (eg, pioglitazone) may cause fluid retention when used in combination with insulin, and the risk for edema is higher with 45 mg of pioglitazone vs 15 mg or 30 mg pioglitazone

Basal insulin: requires 1 injection per day; it limits hepatic glucose production, which limits hyperglycemia overnight and between meals; long-acting basal insulins (specifically analog insulins) are associated with less symptomatic and nocturnal hypoglycemia, compared with human insulin (eg, Neutral Protamine Hagedorn [NPH]); the starting dose can range from 0.1 to 0.2 U/kg/day; NPH activity peaks after ≈6 hr; NPH dosing at bedtime is preferable to dosing at dinnertime to reduce risk for hypoglycemia while sleeping; otherwise, morning vs evening dosing of basal insulin does not seem to matter; basal insulin can be titrated every few days with fasting glucose as a target, but beware of overbasalization; >0.5 U/kg insulin may produce hypoglycemia or a decrease of glucose level by >50 mg/dL overnight; failure of patients to check blood sugar or lack of access to continuous glucose monitoring (CGM) is a major challenge for insulin management; advise patients to check glucose at bedtime or several hours after dinner, or use CGM

Regular U-500 insulin (U-500R; Humulin): especially helpful for individuals taking >200 U insulin daily, who usually have obesity but may also have, eg, acromegaly, Cushing syndrome; to prevent pain from injecting large volumes of insulin, start dosing with 80% of the patient’s total dose of U-100R if HbA_1C is well-controlled; studies showed no differences with regard to HbA_1C outcomes or occurrence of hypoglycemia with U-500R dosing twice vs three times a day; U-500R is often dosed three times daily before meals; administer full U-500R dosing if HbA_1C >8%; U-500R is available through an insulin pen or a vial, and studies show that U-500R is more cost-effective compared with other forms of insulin; dose peaking is less pronounced with U-500R, compared with U-100R; U-500R remains in the body longer than U-100R; instruct patients to increase insulin dose by a few units every 2 to 3 days until improved glucose control is noted, though not all patients are comfortable with that; the key is to reach patients (through use of a diabetes educator or clinical pharmacist) between office visits to avoid prolonged periods without dose adjustment

Prandial insulin: many patients require prandial insulin but not necessarily with every meal; it can be helpful to initially limit prandial insulin to one dose with the largest meal; start with 10% of the basal dose (typically 4 to 6 units with the largest meal), and adjust dose every few days if needed; consider reducing the basal dose prior to initiating prandial insulin for patients with better glucose control, those nearing a dose of 0.5 units/kg, or with concern for overnight hypoglycemia; consider discontinuing sulfonylurea agents before initiating prandial insulin to reduce risk for hypoglycemia; it is preferable to consider adding a morning dose of NPH for patients already taking NPH once nightly, compared with initiating prandial insulin

Inhaled insulin: inhaled insulin peaks earlier and has a shorter half-life, compared with subcutaneous insulin; effective for management of postprandial hyperglycemia; long-term data are insufficient; some concern exists regarding effects of inhaled insulin particles on the lungs; patients cannot smoke or have any kind of significant baseline pulmonary disease (eg, asthma, chronic obstructive pulmonary disease) prior to drug initiation; measure baseline forced expiratory volume, which slightly declines after starting insulin and rebounds upon discontinuation; available in 4U, 8U, and 12U cartridges

Other insulins: people with T2DM benefit from insulin pump therapy or the use of smart, connected insulin pens; mixed insulins may be effective for some individuals and may be the most cost-efficient option; counsel patients regarding over-the-counter availability of human insulin, which may help prevent development of ketoacidosis (especially patients with T1D); ask patients about insulin rationing

Glucagon: newer forms are available; older preparations are insoluble and have complicated processes for administration; newer forms include liquid-soluble glucagon and nasal glucagon and are effective in treating hyperglycemia; offer glucagon to all patients taking insulin for emergency use

Readings

Berget C, Messer LH, Forlenza GP. A clinical overview of insulin pump therapy for the management of diabetes: Past, present, and future of intensive therapy. Diabetes Spectr. 2019;32(3):194-204. doi:10.2337/ds18-0091; Cowart K. Overbasalization: addressing hesitancy in treatment intensification beyond basal insulin. Clin Diabetes. 2020;38(3):304-310. doi:10.2337/cd19-0061a v; King P, Peacock I, Donnelly R. The UK prospective diabetes study (UKPDS): clinical and therapeutic implications for type 2 diabetes. Br J Clin Pharmacol. 1999;48(5):643-8. doi:10.1046/j.1365-2125.1999.00092.x; Mitchell SL, Leon DAC, Chaugai S, et al. Pharmacogenetics of hypoglycemia associated with sulfonylurea therapy in usual clinical care. Pharmacogenomics J. 2020;20(6):831-839. doi:10.1038/s41397-020-0171-4; Shaw KF, Valdez CA. Development and implementation of a U-500 regular insulin program in a federally qualified health center. Clin Diabetes. 2017;35(3):162-167. doi:10.2337/cd16-0057.

Disclosures

For this program, members of the faculty and planning committee reported nothing relevant to disclose.

Acknowledgements

Dr. Lieb was recorded at the 9th Turning the Tide on Diabetes Conference, held on May 13, 2023, in Norfolk, VA, presented by Eastern Virginia Medical School. For information about upcoming CME activities from this presenter, please visit https://www.evms.edu/education/cme. Audio Digest thanks the speakers and presenters for their cooperation in the production of this program.

CME/CE INFO

Accreditation:

The Audio- Digest Foundation is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

The Audio- Digest Foundation designates this enduring material for a maximum of 0.75 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Audio Digest Foundation is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center's (ANCC's) Commission on Accreditation. Audio Digest Foundation designates this activity for 0.75 CE contact hours.

Lecture ID:

IM710202

Expiration:

This CME course qualifies for AMA PRA Category 1 Credits™ for 3 years from the date of publication.

Instructions:

To earn CME/CE credit for this course, you must complete all the following components in the order recommended: (1) Review introductory course content, including Educational Objectives and Faculty/Planner Disclosures; (2) Listen to the audio program and review accompanying learning materials; (3) Complete posttest (only after completing Step 2) and earn a passing score of at least 80%. Taking the course Pretest and completing the Evaluation Survey are strongly recommended (but not mandatory) components of completing this CME/CE course.

Estimated time to complete this CME/CE course:

Approximately 2x the length of the recorded lecture to account for time spent studying accompanying learning materials and completing tests.