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Chronic Intermittent Intravenous Insulin Therapy

Policy Number: MP-603

Latest Review Date:  February 2020

Category:  Medical     

Policy Grade:  D


Chronic intermittent intravenous insulin therapy is considered not medically necessary and 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 a state of increased hepatic glucose production, decreased peripheral glucose update, and decreased insulin secretion (type 2 diabetes).

The different classes of diabetic drug therapy target different aspects of glucose metabolism. Various insulin secretagogues (e.g., sulfonylureas) function by increasing the pancreatic secretion of insulin; thiazolidinediones (e.g., pioglitazone [Actos®] and rosiglitazone [Avandia®]) function in part by increasing glucose uptake in the peripheral (principally skeletal) tissues; and biguanides (e.g., metformin) function by decreasing hepatic glucose production. While patients with type 2 diabetes may be treated with various combinations of all three of these classes of drugs, without or without additional insulin, patients with type 1 diabetes, who have no baseline insulin secretion, receive exogenous insulin therapy. Standard insulin management involves the use of subcutaneous injection to mimic a physiologic insulin profile. Intravenous insulin is used in the acute, inpatient setting for the management of hyperglycemic emergencies (i.e., diabetic ketoacidosis).


This policy was based on a search of the MEDLINE database through December 09, 2019.


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 the effects of the technology on health outcomes.


The American Diabetes Association (ADA) “Standards of Medical Care in Diabetes” 2019 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. The pharmacologic approaches to glycemic treatment are summarized in chapter 9.


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.  FEP does not consider investigational if FDA approved and will be reviewed for medical necessity.


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


 Glucose, blood by glucose monitoring device(s) cleared by the FDA specifically for home use


 Oxygen uptake, expired gas analysis; rest, indirect (separate procedure)


 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)


 Infusion, normal saline solution, 250 cc


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


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.



  1. American Diabetes Association. Clinical Practice Recommendations 2009. Diabetes Care 2009; 32(suppl 1). //
  2. American Diabetes Association (ADA). American Diabetes Association. Standards of Medical Care in Diabetes - 2017. Accessed January 23, 2017.
  3. Aoki TT, Benbarka MM, Okimura MC, et al. Long-term intermittent intravenous insulin therapy and type 1 diabetes mellitus. Lancet. Aug 28 1993;342(8870):515-518.
  4. Aoki TT, Grecu EO, Arcangeli MA. Chronic intermittent intravenous insulin therapy corrects orthostatic hypotension of diabetes. Am J Med. Dec 1995;99(6):683-684.
  5. Aoki TT, Grecu EO, Prendergast JJ, et al. Effect of chronic intermittent intravenous insulin therapy on antihypertensive medication requirements in IDDM subjects with hypertension and nephropathy. Diabetes Care. Sep 1995;18(9):1260-1265.
  6. Association AD. NA. Diabetes Care, 2019 Dec. 22; 43 (Suppl 1)
  7. Dailey GE, Boden GH, Creech RH, et al. Effects of pulsatile intravenous insulin therapy on the progression of diabetic nephropathy. Metabolism. Nov 2000;49(11):1491-1495.
  8. 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.
  9. 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.
  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. Pharmacologic Approaches to Glycemic Treatment: Standards of Medical Care in Diabetes-2019. Diabetes Care. Jan 2019;42(Suppl 1):S90-s102.
  12. 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.
  13. 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.
  14. Rodbard HW, Blonde L, Braithwaite SS, et al. American Association of Clinical Endocrinologists medical guidelines for clinical practice for the management of diabetes mellitus. Endocr Pract. May-Jun 2007; 13 Suppl 1:1-68.
  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.

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.