Insulin Therapy Review

Educational Objectives

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

1. Distinguish among different types of insulin based on onset of action, peak time, duration, and concentration.

2. Provide patients with effective options for insulin therapy.

3. Compare concentrated insulin with nonconcentrated insulin.

 

Summary

History of use and development of insulin: 1922 — clinical use of insulin began; 1950 — insulin isophane suspension (neutral protamine Hagedorn [NPH]) available; 1953 — insulin zinc suspension, extended (ultralente), available; 1982 — first biosynthetic human insulin available; 1994 — U-500 insulin available; 1996 — insulin lispro injection (Humalog) available; 2000 — long-acting insulin glargine injection (Lantus) available; 2013 — ultralong-acting insulin degludec injection (Tresiba) available; 2014 — biosimilar insulin glargine injection (Basaglar) available in Europe; 2015 — insulin inhalation powder (Afrezza) available; 2016 — concentrated insulin pens available; 2017 — ultrafast-acting insulin available

Categories of insulin: based on onset of action, peak time (time to maximum effect), duration, and concentration (eg, U-100 [100 U/mL])

Intermediate-acting insulin: insulin isophane suspension (NPH; eg, Novolin N, Humulin N) effective and inexpensive; shake before use; onset of action 1 to 2 hr; peak time 4 to 6 hr; duration 12 hr (given twice daily); peak time for small doses earlier; for higher doses, peak time longer

Premixed insulin: insulin isophane suspension premixed with regular insulin; insulin isophane suspension premixed with insulin lispro suspension (eg, Humalog 75/25, Humalog 50/50); insulin isophane suspension premixed with insulin aspart suspension (NovoLog)

Short-acting insulin: “regular” insulin; onset of action 30 to 60 min; peak time 2 to 4 hr; with larger doses, onset of action faster, but peak time and duration longer; U-500 — concentrated regular insulin with long duration of action; profile similar to that of insulin isophane; given 2 to 3 times daily

Rapid- or fast-acting insulin: insulin lispro; insulin aspart; insulin glulisine (Apidra); all insulin analogues; onset of action 5 to 10 min; peak time 60 to 120 min; duration of higher doses longer (5-6 hr); used in insulin pumps

Long-acting insulin: insulin glargine; insulin detemir (Levemir); absorbed slowly; peak effect minimal (risk for hypoglycemia low); onset of action 1 to 2 hr; action plateaus over 12 to 24 hr; insulin glargine stronger than insulin detemir (higher dose of insulin detemir than insulin glargine required for same coverage); twice-daily dosing may be required for insulin detemir (insulin glargine can be used once daily)

Ultralong-acting insulin (insulin degludec): steady state achieved after ≈2 days, so drug can be taken at any time (eg, day, night [helpful for forgetful patients or those with variations in schedule]); associated with lower risk for nocturnal hypoglycemia

Ultrafast-acting insulin (insulin aspart injection [Fiasp]: vitamin B3 and amino acid added to insulin for stability and faster absorption; enters bloodstream in 2.5 min

Inhaled insulin: blisters of insulin available as 4, 8, or 12 U; convenient; expensive; enters bloodstream in 1 min; effective; contraindicated in patients with asthma or chronic obstructive pulmonary disease; measure forced expiratory volume in first second of expiration before initiation, after 6 mo of use, and annually thereafter

Biosimilar insulin glargine: not same as generic insulin glargine; approved by US Food and Drug Administration as biologic agent; similar to insulin glargine, but structure may differ; clinical activity identical to that of insulin glargine; generic agent vs biosimilar agent — clinical trial not required for generic agent; ≥1 clinical trial required for biosimilar product; indications for biosimilar product similar to those of reference product; generic agent and biosimilar agent not interchangeable; generic agent significantly less expensive

Concentrated insulin (eg, U-500, U-300, U-200): allows for use of lower volume, better absorption, and longer duration

Guidelines of American Diabetes Association: discuss importance of diet and exercise with patients; A1c <9% — start with monotherapy (metformin); A1c ≥9% — consider dual therapy; A1c ≥10% or glucose level >300 mg/dL, and patient symptomatic — consider combination injectable therapy; initiation of basal insulin — start with 10 U/day (or dose based on weight and insulin resistance); increase dose by 10% to 15% (or by 2-4 U) once or twice weekly to reach goal for fasting blood glucose (FBG); after FBG level at goal and A1c level decreases, consider prescribing short-acting insulin taken with largest meal

Switching between types of insulin: least expensive insulins short-acting (regular) insulin and intermediate-acting insulins (insulin isophane); when switching from long-acting insulin (insulin glargine) to insulin isophane, use 50% of total daily dose in morning and 50% in evening; when switching from long-acting to premixed insulin, use ≈66% of total daily dose in morning and ≈33% in evening; if switching between biosimilar insulin glargine and insulin glargine, no adjustments needed; reasons for switching insulins include financial considerations and insurance coverage

Conclusion: give patients algorithm for self-titration of doses of insulin; cost-effectiveness of insulin important in decision making

Questions and answers: delivery of inhaled insulin — consistent when proper technique used; diabetes mellitus and elevated levels of insulin antibodies — not highly concerning when insulin analogues and synthetic insulin used; insulin resistance — significant problem; concentrated insulin appropriate because of lower volume and better absorption; diet and exercise important; associated with metabolic syndrome; starting insulin in elderly patient — check A1c level; determine whether insulin necessary; patient-centered approach important (consider comorbidities, life expectancy, dexterity, and risk for hypoglycemia); newer types of insulins — evidence that newer, more expensive insulin more effective than older, less expensive insulin lacking; insulin and weight gain — insulin causes weight gain (only insulin detemir weight-neutral); encourage diet and exercise; decrease dose of insulin; glucagon-like peptide-1 analogues can be given in conjunction with insulin to maintain stable weight; storage of insulin — avoid extreme temperatures and direct sunlight; room temperature appropriate; efficacy of insulin decreases after 30 days

 

Readings

Chamberlain JJ et al: Diagnosis and management of diabetes: synopsis of the 2016 American Diabetes Association Standards of Medical Care in Diabetes. Ann Intern Med. 2016 Apr 19;164(8):542-52; Chan J, Cheng-Lai A: Inhaled insulin: a clinical and historical review. Cardiol Rev. 2017 May/Jun;25(3):140-146; Frier BM et al: A comparison of insulin detemir and neutral protamine Hagedorn (isophane) insulin in the treatment of diabetes: a systematic review. Diabetes Obes Metab. 2013 Nov;15(11):978-86; Peters AL et al: Biosimilars and new insulin versions. Endocr Pract. 2015 Dec;21(12):1387-94; Schloot NC et al: Concentrated insulins in current clinical practice. Diabetes Res Clin Pract. 2018 Dec 21 [Epub ahead of print]; Tibaldi J, Rakel RE: Why, when and how to initiate insulin therapy in patients with type 2 diabetes. Int J Clin Pract. 2007 Apr;61(4):633-44.

Disclosures

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

Acknowledgements

Dr. Chu was recorded in San Diego, CA, at the Family Medicine Update 2018: 61st Annual Postgraduate Symposium, presented on June 22-24, 2018, by the San Diego Academy of Family Physicians. Please visit www.sandiegoafp.org/events for information about upcoming events from this sponsor. The Audio Digest Foundation thanks the speakers and sponsors 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 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 CE contact hours.

Lecture ID:

FP670801

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.

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