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Chronic Intermittent Intravenous Insulin Therapy

Policy Number: MP-603

Latest Review Date:  February 2024

Category:  Medical     


Chronic intermittent intravenous insulin therapy is investigational.

This policy does not apply to the use of intravenous insulin infusions in the inpatient setting (i.e., for the treatment of diabetic ketoacidosis or diabetic hyperosmolar coma).


Chronic intermittent intravenous insulin therapy (CIIIT) is a technique for delivering variable-dosage insulin to diabetic patients with the goal of improved long-term glycemic control. Through an unknown mechanism, it is postulated to induce insulin-dependent hepatic enzymes to suppress glucose production.

Glucose Homeostasis

Insulin-mediated glucose homeostasis involves 3 primary functions that occur at 3 locations:(1) insulin secretion by the pancreas; (2) glucose uptake, primarily in the muscle, liver, gut, and fat; and (3) hepatic glucose production. In the fasting state, when insulin levels are low, most glucose uptake is non-insulin-mediated. Glucose uptake is then balanced by liver production of glucose. However, after a glucose challenge, insulin binds to specific receptors on the hepatocyte to suppress glucose production. Without this inhibition, as can be seen in diabetic patients, marked hyperglycemia may result.

Medications Used for Glucose Homeostasis in Diabetes

Diabetes is characterized by elevated blood glucose levels due to inadequate or absent insulin production (type 1 diabetes) or due to increased hepatic glucose production, decreased peripheral glucose uptake, and decreased insulin secretion (type 2 diabetes).

Patients with type 1 diabetes require insulin therapy. Insulin therapy for patients with type 1 diabetes usually consists of multiple daily subcutaneous injections with both basal and meal time insulin or continuous subcutaneous insulin infusions given through an insulin pump. Insulin therapy has improved over the last several decades with newer insulin products providing improved pharmacokinetic parameters to closer mimic physiologic insulin. Intravenous insulin is used in the acute inpatient setting to manage hyperglycemic emergencies (e.g., diabetic ketoacidosis).


This evidence review has been updated regularly with searches of the PubMed database. The most recent literature update was performed through December 19, 2023.


For individuals who have type 1 diabetes who receive CIIT, the evidence includes 2 randomized controlled trials and several uncontrolled studies. Relevant outcomes are symptoms, change in disease status, and treatment-related morbidity. A limited number of uncontrolled studies suggest that CIIIT may improve glycemic control. The 2 RCTs report that CIIIT may moderate the progression of nephropathy or retinopathy. However, the published studies are small and report benefits on intermediate outcomes only (i.e., changes in laboratory values). The clinical significance of the differences reported in the studies is uncertain. Additionally, most published evidence appeared between 1993 and 2010 and as a result, does not account for more recent improvements in diabetes care. The evidence is insufficient to determine that the technology results in an improvement in net health outcomes.


American Diabetes Association

The 2024 American Diabetes Association (ADA) “Standards of Care in Diabetes” includes ADA’s current clinical practice recommendations and is intended to provide the components of diabetes care, general treatment goals and guidelines, and tools to evaluate quality of care. There is no mention of chronic intermittent intravenous insulin therapy (CIIIT).

American Association of Clinical Endocrinology

In 2022, the American Association of Clinical Endocrinology updated its 2015 clinical practice guideline for developing a diabetes mellitus comprehensive care plan. The guideline includes evidence-based recommendations for the comprehensive care of people with both type 1 and type 2 diabetes; recommendations are divided up into 4 sections: screening, diagnosis, targets, and monitoring; comorbidities and complications; management; education and new topics regarding diabetes. There is no mention of CIIIT.


Not applicable.


CIIIT, variable dosage insulin, hepatic activation, Outpatient Intravenous Insulin Therapy, OIVIT, metabolic activation therapy, MAT®, pulsatile intravenous insulin therapy (PIVIT), pulsatile insulin therapy (PIT), Artificial Pancreas Treatment®, APT®


Any insulin infusion pump can be used for the purposes of chronic intermittent intravenous therapy.  Infusion pumps have been cleared for marketing by the U.S. Food and Drug Administration (FDA) through the 510(k) process.  FDA determined that this device was substantially equivalent to existing devices for the delivery of intravenous medications.


Coverage is subject to member’s specific benefits. Group-specific policy will supersede this policy when applicable.

ITS: Home Policy provisions apply.

FEP: Special benefit consideration may apply. Refer to member’s benefit plan.  


There is no specific CPT code describing CIIIT.

The following series of CPT codes and HCPCS J codes may be used to describe the various components of CIIIT. Some codes, such as the code for glucose testing, may be used more than once during a single session of CIIIT.


 Glucose; blood reagent strip


 Intravenous infusion, for therapy, prophylaxis, or diagnosis (specify substance or drug); initial, up to one hour


  ; each additional hour (List separately in addition to code for primary procedure)


There is a HCPCS code was created specific to this therapy:


 Outpatient intravenous insulin treatment (OIVIT) either pulsatile or continuous, by any means, guided by the results of measurements for: respiratory   quotient,   and/or, urine urea nitrogen (UUN), and/or, arterial, venous or capillary glucose, and/or potassium concentration.


 Infusion, normal saline solution, 250 cc


 Insulin for administration through DME (i.e., insulin pump) per 50 units


  1. American Diabetes Association (ADA). American Diabetes Association. Standards of Medical Care in Diabetes - 2017.
  2. American Diabetes Association. 9. Pharmacologic Approaches to Glycemic Treatment: Standards of Medical Care in Diabetes-2021. Diabetes Care. Jan 2021; 44(Suppl 1): S111-S124.
  3. American Diabetes Association. 2. Classification and Diagnosis of Diabetes: Standards of Medical Care in Diabetes-2019. Diabetes Care. 2019 Jan;42(Suppl 1):S13-S28. doi: 10.2337/dc19-S002.
  4. Blonde L, Umpierrez GE, Reddy SS, et al. American Association of Clinical Endocrinology Clinical Practice Guideline:Developing a Diabetes Mellitus Comprehensive Care Plan-2022 Update. Endocr Pract. Oct 2022; 28(10): 923-1049.
  5. Draznin B, Aroda VR, Bakris G, et al. 9. Pharmacologic Approaches to Glycemic Treatment: Standards of Medical Care inDiabetes-2022. Diabetes Care. Jan 01 2022; 45(Supplement_1): S125-S143.
  6. ElSayed NA, Aleppo G, Bannuru RR, et al. Pharmacologic Approaches to Glycemic Treatment: Standards of Care in Diabetes-2024.Diabetes Care. Jan 01 2024; 47(Suppl 1): S158-S178.
  7. Handelsman Y, Mechanick JI, Blonde L, et al. American Association of Clinical Endocrinologists Medical Guidelines for Clinical Practice for developing a diabetes mellitus comprehensive care plan. Endocr Pract. Mar-Apr 2011;17 Suppl 2:1-53.
  8. Handelsman Y, Bloomgarden ZT, Grunberger G, et al. American Association of Clinical Endocrinologists and American College of Endocrinology - clinical practice guidelines for developing a diabetes mellitus comprehensive care plan - 2015. Endocr Pract. Apr 2015; 21 Suppl 1:1-87.
  9. IOM (Institute of Medicine). 2011. Clinical Practice Guidelines We Can Trust. Washington, DC: The National Academies Press.
  10. Kansagara D, Fu R, Freeman M, et al. Intensive insulin therapy in hospitalized patients: a systematic review. Ann Intern Med. Feb 15 2011;154(4):268-282.
  11. Mirbolooki MR, Taylor GE, Knutzen VK, et al. Pulsatile intravenous insulin therapy: the best practice to reverse diabetes complications?. Med Hypotheses. Sep 2009; 73(3): 363-9.
  12. Pharmacologic Approaches to Glycemic Treatment: Standards of Medical Care in Diabetes-2019. Diabetes Care. Jan 2019;42(Suppl 1):S90-s102.
  13. Qaseem A, Chou R, Humphrey LL, et al. Inpatient glycemic control: best practice advice from the Clinical Guidelines Committee of the American College of Physicians. Am J Med Qual. Mar-Apr 2014; 29(2):95-98.
  14. Qaseem A, Humphrey LL, Chou R, et al. Use of intensive insulin therapy for the management of glycemic control in hospitalized patients: a clinical practice guideline from the American College of Physicians. Ann Intern Med. Feb 15 2011; 154(4):260-267.
  15. Weinrauch LA, Sun J, Gleason RE, et al. Pulsatile intermittent intravenous insulin therapy for attenuation of retinopathy and nephropathy in type 1 diabetes mellitus. Metabolism. Mar 1 2010; 59(10):1429-1434.


Medical Policy Panel, July 2015

Medical Policy Group, July 2015 (6):  New policy, previously on Investigational Listing; remains investigational.

Medical Policy Administration Committee, July 2015

Available for comment July 21 through September 4, 2015

Medical Policy Group, October 2015 (6):  Updates to Key Words and Coding; no change to policy statement

Medical Policy Panel, February 2016

Medical Policy Group, February 2016 (6):  Updates to Key Points and Key Words; no change in policy statement.

Medical Policy Panel, February 2017

Medical Policy Group, February 2017 (6): Updates to Description, Key Points, Practice Guidelines and References. No change to policy statement.

Medical Policy Panel, February 2018

Medical Policy Group, February 2018 (6): Updates to Description, Key Points, Removed Coding 94681, 99070 & 99211, and References.

Medical Policy Panel February 2019

Medical Policy Group, February 2019 (6): Updates Description, Key Points, Practice Guidelines and References.

Medical Policy Panel, February 2020

Medical Policy Group, February 2020 (6): Updates to Key Points and References.

Medical Policy Panel, February 2021

Medical Policy Group, February 2021 (6): Updates to Description, Key Points, Practice Guidelines and References.

Medical Policy Panel, February 2022

Medical Policy Group, February 2022 (6): Updates to Key Points, Practice Guidelines, Current Coding (removed 82962/94690) and References.

Medical Policy Panel, February 2023

Medical Policy Group, February 2023 (6): Updates to Key Points, Practice Guidelines, Benefit Application and References.

Medical Policy Group, February 2024

Medical Policy Panel, February 2024 (6): Updates to Key Points, Practice Guidelines and References.

This medical policy is not an authorization, certification, explanation of benefits, or a contract. Eligibility and benefits are determined on a case-by-case basis according to the terms of the member’s plan in effect as of the date services are rendered. All medical policies are based on (i) research of current medical literature and (ii) review of common medical practices in the treatment and diagnosis of disease as of the date hereof. Physicians and other providers are solely responsible for all aspects of medical care and treatment, including the type, quality, and levels of care and treatment.

This policy is intended to be used for adjudication of claims (including pre-admission certification, pre-determinations, and pre-procedure review) in Blue Cross and Blue Shield’s administration of plan contracts.

The plan does not approve or deny procedures, services, testing, or equipment for our members. Our decisions concern coverage only. The decision of whether or not to have a certain test, treatment or procedure is one made between the physician and his/her patient. The plan administers benefits based on the member’s contract and corporate medical policies. Physicians should always exercise their best medical judgment in providing the care they feel is most appropriate for their patients. Needed care should not be delayed or refused because of a coverage determination.

As a general rule, benefits are payable under health plans only in cases of medical necessity and only if services or supplies are not investigational, provided the customer group contracts have such coverage.

The following Association Technology Evaluation Criteria must be met for a service/supply to be considered for coverage:

1. The technology must have final approval from the appropriate government regulatory bodies;

2. The scientific evidence must permit conclusions concerning the effect of the technology on health outcomes;

3. The technology must improve the net health outcome;

4. The technology must be as beneficial as any established alternatives;

5. The improvement must be attainable outside the investigational setting.

Medical Necessity means that health care services (e.g., procedures, treatments, supplies, devices, equipment, facilities or drugs) that a physician, exercising prudent clinical judgment, would provide to a patient for the purpose of preventing, evaluating, diagnosing or treating an illness, injury or disease or its symptoms, and that are:

1. In accordance with generally accepted standards of medical practice; and

2. Clinically appropriate in terms of type, frequency, extent, site and duration and considered effective for the patient’s illness, injury or disease; and

3. Not primarily for the convenience of the patient, physician or other health care provider; and

4. Not more costly than an alternative service or sequence of services at least as likely to produce equivalent therapeutic or diagnostic results as to the diagnosis or treatment of that patient’s illness, injury or disease.