insulin for injection (Novolin, Humulin, Lente, Semilente, Ultralente, Iletin, NPH (isophane), PZI, INS)
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Introduction
Tradenames: Iletin, Novolin, Humilin.
Indications
Contraindications
Dosage
- maintenance 0.5-1 unit/kg/day (doses vary)
- no maximum dose[11]
- severe hyperkalemia: 5-10 units regular plus concurrent IV dextrose
- profound hyperglycemia/diabetic ketoacidosis (DKA):
- infusion 100 units regular in 500 mL of normal saline (0.2 units/mL), at 0.1 units/kg/hr [allow 100 mL to drain & prime tubing prior to hook-up] 70 kg: 7 units/hr (35 mL/hr)
- see insulin sliding scale
- conventional SQ dosing (simple):
- insulin 70/30 (70% NPH/30% regular) 2/3 in AM, 1/3 in PM
- convenient inexpensive
- may result in more frequent episodes of hypoglycemia & weight gain[4]
- intensified SQ therapy (better but more complex)
- NPH given QHS selectively reduces fasting hypoglycemia & minimizes weight gain[4]
- avoid injection of > 2.5 mL SQ at any one site[11]
Injection:
- 100 units/mL, 10 mL (U-100)
- insulin lispro 200 units/mL (U-200)[21]
- degludec 200 units/mL (U-200)
- glargine 300 units/mL (U-300)
- icodec (weekly, investigational)[23]
- regular insulin, 500 units/mL (U-500)[21]
Storage:
- manufacturers recommend refrigerating unopened insulin vials & storing them at room temperature <= 45 days once opened
- several types of insulin can be stored at 25 C for <= 6 months & at 37 C for <= 2 months[25]
Dosage adjustment in renal failure
Table
| creatinine clearance | dose |
|---|---|
| 10-50 mL/min | 75% |
| < 10 mL/min | 25-50% |
Pharmacokinetics
Table
| Preparation | Onset (hr) | Peak (hr) | Duration (hr) | Class |
|---|---|---|---|---|
| Lispro | 15-30 min | 0.5-2.5 | 3-6.5 | rapid |
| Aspart | 10-20 min | 1-3 | 3-5 | rapid |
| Glulisine | 10-15 min | 1-1.5 | 3-5 | rapid |
| Regular | 0.5-1 | 2.5-5 | 6-8 | short |
| Semilente | 1-1.5 | 5-10 | 12-16 | intermediate |
| NPH (isophane) | 1-1.5 | 4-12 | 24 | intermediate |
| Lente | 1-2.5 | 7-15 | 24 | intermediate |
| PZI | 4-8 | 14-24 | 36 | long |
| Ultralente | 4-8 | 10-20 | 24-28 | long |
| Glargine | 1.1 | none | 24 | long |
| Detemir | 3-4 | 6-8 | 12-24 | long |
| Degludec | 1 | 12 | > 40 | long |
| Icodec (weekly, investigational)[23] | ||||
| Novolin* 70/30 | 0.5-1.0 | 4-12 | 18-24 | mixture |
| Humulin* 50/50 | 0.5 | 2-5.5 | 18-24 | mixture |
| Novolog# 70/30 | <0.5-1.0 | 1-4 | 15-18 | mixture |
| Humalog% 75/25 | <0.5-1.0 | 1.6.5 | 10-16 | mixture |
| Afrezza | 15 min | 1 | 3-4 | inhalation |
* NPH/regular; Also Humulin 70/30
# Novolog 70/30 is Aspart 30%/Aspart protamine 70%
% Humalog 75/25 is Lispro 25%/Lispro protamine 75%
Adverse effects
- not common (1-10%)
- hypoglycemia*, perspiration, palpitations, tachycardia, tingling of fingers, tremors, confusion, fatigue, loss of consciousness, headache, urticaria, anaphylaxis, hypothermia, hunger, pallor, nausea, numbness of mouth, itching, redness, swelling, stinging, warmth at injection site, atrophy or hypertrophy of subcutaneous fat tissue, muscle weakness, transient presbyopia, blurred vision
- other
- transient edema[4]
- insulins associated with increased risk of pancreatic cancer (RR=2.41) & liver cancer (RR=1.74)[24]
- increased risk of frailty[26]
- not associated with increased risk of breast cancer (RR=0.90) or prostate cancer (RR= 0.74)[24]
* Caution: avoid exercise within 4 h of regular insulin
* 25% of insulin errors lead to patient harm[16]
* insulin is involved in ~ 1/3 of fatal medication errors[16]
Drug interactions
- agents that increase hypoglycemic effect
- agents that decrease hypoglycemic effect
Mechanism of action
- actions via insulin protein & insulin receptor
- decreases serum glucose
- improved pancreatic islet beta cell function
- decreased insulin resistance
Notes
- average annual costs for insulin:
More general terms
More specific terms
Additional terms
- anti-insulin antibody
- insulin device (device for administering insulin)
- insulin in serum
- insulin protein
- insulin receptor antagonist (insulin antagonist)
- insulin receptor; IR; (INSR)
- insulin resistance
- insulin sliding scale (ISS)
References
- ↑ The Pharmacological Basis of Therapeutics, 9th ed. Gilman et al, eds. Permagon Press/McGraw Hill, 1996
- ↑ Drug Information & Medication Formulary, Veterans Affairs, Central California Health Care System, 1st ed., Ravnan et al eds, 1998
- ↑ Kaiser Permanente Northern California Regional Drug Formulary, 1998
- ↑ 4.0 4.1 4.2 4.3 Medical Knowledge Self Assessment Program (MKSAP) 11, 16. 18. American College of Physicians, Philadelphia 1998, 2012, 2018
- ↑ 5.0 5.1 Journal Watch 21(5):44, 2001 Cefalu WT et al; Inhaled Insulin Study Group. Inhaled human insulin treatment in patients with type 2 diabetes mellitus. Ann Intern Med. 2001 Feb 6;134(3):203-7. PMID: https://www.ncbi.nlm.nih.gov/pubmed/11177333
Nathan DM. Inhaled insulin for type 2 diabetes: solution or distraction?. Ann Intern Med. 2001 Feb 6;134(3):242-4. No abstract available. PMID: https://www.ncbi.nlm.nih.gov/pubmed/11177338 - ↑ Locus Link http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=3630
- ↑ Insulins Prescriber's Letter 10(8):41 2004 Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=190806&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ 8.0 8.1 Prescriber's Letter 12(9): 2005 Diabetes Drugs on the Horizon Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=210905&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ Prescriber's Letter 13(3): 2006 Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=220309&pb=PRL Comparison of Insulins (subscription needed) http://www.prescribersletter.com
- ↑ Prescriber's Letter 15(11): 2008 Insulin Use in Patients With Type 2 Diabetes Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=241120&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ 11.0 11.1 11.2 Prescriber's Letter 16(1): 2009 COMMENTARY: How Much Insulin Is Too Much? CHART: Comparison of Insulins Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=250107&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ Prescriber's Letter 16(8): 2009 COMMENTARY: Is Lantus Associated With An Increased Risk of Cancer? CHART: Comparison of Insulins Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=250802&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ Prescriber's Letter 16(10): 2009 CHART: How to Switch Between Insulin Products CHART: Initiation and Adjustment of Insulin Regimens for Type 2 Diabetes CHART: Comparison of Insulins Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=251005&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ Testa MA et al. Comparative effectiveness of basal-bolus versus premix analog insulin on glycemic variability and patient-centered outcomes during insulin intensification in type 1 and type 2 diabetes: A randomized, controlled, crossover trial. J Clin Endocrinol Metab 2012 Oct; 97:3504. PMID: https://www.ncbi.nlm.nih.gov/pubmed/22851487
- ↑ Zinman B et al. Insulin degludec versus insulin glargine in insulin-naive patients with type 2 diabetes: A 1-year, randomized, treat-to-target trial (BEGIN Once Long). Diabetes Care 2012 Dec; 35:2464 PMID: https://www.ncbi.nlm.nih.gov/pubmed/23043166
- ↑ 16.0 16.1 16.2 Prescriber's Letter 21(7): 2014 Tips to Improve Insulin Safety Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=300713&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ Prescriber's Letter 22(8): 2015 (subscription needed) CHART: Comparison of Insulins and Injectable Diabetes Meds CHART: Tips to Improve Insulin Safety Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=310825&pb=PRL http://www.prescribersletter.com
- ↑ DeWitt DE, Hirsch IB. Outpatient insulin therapy in type 1 and type 2 diabetes mellitus: scientific review. JAMA. 2003 May 7;289(17):2254-64. Review. PMID: https://www.ncbi.nlm.nih.gov/pubmed/12734137
- ↑ 19.0 19.1 Hua X, Carvalho N, Tew M, Huang ES, Herman WH, Clarke P. Expenditures and Prices of Antihyperglycemic Medications in the United States: 2002-2013. JAMA. 2016 Apr 5;315(13):1400-1402. PMID: https://www.ncbi.nlm.nih.gov/pubmed/27046369
- ↑ 20.0 20.1 Herkert D, Vijayakumar P, Luo J et al. Cost-related insulin underuse among patients with diabetes. JAMA Intern Med 2018 Dec 3 PMID: https://www.ncbi.nlm.nih.gov/pubmed/30508012 https://jamanetwork.com/journals/jamainternalmedicine/article-abstract/2717499
- ↑ 21.0 21.1 21.2 Schloot NC, Hood RC, Corrigan SM, Panek RL, Heise T. Concentrated insulins in current clinical practice. Diabetes Res Clin Pract. 2019 Feb;148:93-101. PMID: https://www.ncbi.nlm.nih.gov/pubmed/30583034 Free article. Review.
- ↑ NEJM Knowledge+ Endocrinology
- ↑ 23.0 23.1 23.2 Rosenstock J, Bain SC, Gowda A et al Weekly Icodec versus Daily Glargine U100 in Type 2 Diabetes without Previous Insulin. N Engl J Med. 2023. June 24 PMID: https://www.ncbi.nlm.nih.gov/pubmed/37356066 https://www.nejm.org/doi/full/10.1056/NEJMoa2303208
Lingvay I, Asong M, Desouza C et al Once-Weekly Insulin Icodec vs Once-Daily Insulin Degludec in Adults With Insulin-Naive Type 2 Diabetes. The ONWARDS 3 Randomized Clinical Trial. N Engl J Med. 2023. June 24 PMID: https://www.ncbi.nlm.nih.gov/pubmed/37354562 https://jamanetwork.com/journals/jama/fullarticle/2806635 - ↑ 24.0 24.1 24.2 Chen Y et al Diabetes medications and cancer risk associations: a systematic review and meta-analysis of evidence over the past 10 years. Sci Rep. 2023 13(1):11844. July 22. PMID: https://www.ncbi.nlm.nih.gov/pubmed/37481610 PMCID: PMC10363143 Free PMC article https://rdcu.be/dh4Er
- ↑ 25.0 25.1 Harris E Insulin Maintains Activity While Stored Unrefrigerated. JAMA. Published online November 15, 2023 PMID: https://www.ncbi.nlm.nih.gov/pubmed/37966849 https://jamanetwork.com/journals/jama/fullarticle/2812200
- ↑ 26.0 26.1 Nishimura A et al Older Adults with Type 2 Diabetes: A Cross-Sectional Study. Drugs Aging. 2024. May 24 Not indexed in PubMed https://link.springer.com/article/10.1007/s40266-024-01119-8