Chronic Intermittent Intravenous Insulin Therapy Form

500 EXCHANGE STREET, PROVIDENCE, RI 02903-2699 MEDICAL COVERAGE POLICY | 1 (401) 274-4848 WWW.BCBSRI.COM EFFECTIVE DATE: 05|01|2017 POLICY LAST REVIEWED: 04|02|2025 OVERVIEW Chronic intermittent intravenous insulin therapy (CIIIT) is a technique for delivering variable-dose insulin to diabetic patients with the goal of improved long-term glycemic control. Through an unknown mechanism, CIIIT is postulated to induce insulin-dependent hepatic enzymes to suppress glucose production. MEDICAL CRITERIA Not applicable PRIOR AUTHORIZATION Not applicable POLICY STATEMENT Medicare Advantage Plans Chronic intermittent intravenous insulin therapy is considered not covered as the evidence is insufficient to determine the effects of the technology on health outcomes. Commercial Products Chronic intermittent intravenous insulin therapy is considered not medically necessary as the evidence is insufficient to determine the effects of the technology on health outcomes. COVERAGE Benefits may vary between groups and contracts. Please refer to the appropriate Benefit Booklet, Evidence of Coverage, or Subscriber Agreement for applicable not medically necessary/not covered benefits/coverage. BACKGROUND Glucose Homeostasis Insulin-mediated glucose homeostasis involves 3 primary functions, which 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 into cells is noninsulin-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, marked hyperglycemia may result. Medications 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 mealtime 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 (eg, diabetic ketoacidosis). Chronic Intermittent Insulin Therapy Several forms of chronic intermittent insulin therapy, in which insulin is delivered intravenously or into the peritoneal space, have been evaluated. Medical Coverage Policy | Chronic Intermittent Intravenous Insulin Therapy

500 EXCHANGE STREET, PROVIDENCE, RI 02903-2699 MEDICAL COVERAGE POLICY | 2 (401) 274-4848 WWW.BCBSRI.COM

Chronic intermittent intravenous insulin therapy, also referred to as outpatient intravenous insulin therapy, pulsatile intravenous insulin therapy, hepatic activation therapy, or metabolic activation therapy involves delivering insulin intravenously once weekly over several hours in a pulsatile fashion using a specialized pump controlled by a computerized program that adjusts the doses based on frequent blood glucose monitoring. CIIIT is principally designed to normalize the hepatic metabolism of glucose. In 1993, Aoki et al proposed that, in patients with type 1 diabetes, lower levels of insulin in the portal vein are associated with a decreased concentration of the liver enzymes required for hepatic metabolism of glucose. They stated: “We reasoned that if the liver of an IDDM [insulin-dependent diabetes mellitus; i.e., type 1 diabetes] patient could be perfused with near-normal concentrations of insulin during meals, the organ could be reactivated,” and proposed that intermittent intravenous pulsatile infusions of insulin administered once weekly while the patient ingests a carbohydrate meal would increase the portal vein concentrations of insulin, ultimately stimulating the synthesis of glucokinase and other insulin-dependent enzymes. The pulses are designed to deliver a higher, more physiologic concentration of insulin to the liver than is delivered by traditional subcutaneous injections. This higher level of insulin is thought to more closely mimic the body’s natural levels of insulin because it is delivered to the liver. The goal of this outpatient therapy is improved glucose control through improved hepatic activation.

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

Medicare Advantage Plans The Centers for Medicare and Medicaid Services (CMS) determines that the evidence is adequate to conclude that outpatient intravenous (IV) insulin therapy (OIVIT) does not improve health outcomes in Medicare beneficiaries. Therefore, CMS determines that OIVIT is not reasonable and necessary for any indication under section 1862(a)(1)(A) of the Social Security Act. Services comprising an Outpatient Intravenous Insulin Therapy regimen are nationally non-covered under Medicare when furnished pursuant to an OIVIT regimen.

CODING Medicare Advantage Plans and Commercial Products The following HCPCS code(s) is not covered for Medicare Advantage Plans and not medically necessary for Commercial Products: G9147 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.

RELATED POLICIES Not applicable

PUBLISHED Provider Update, June 2025 Provider Update, May 2024 Provider Update, May 2023 Provider Update, June 2022 Provider Update, June 2021

REFERENCES

500 EXCHANGE STREET, PROVIDENCE, RI 02903-2699 MEDICAL COVERAGE POLICY | 3 (401) 274-4848 WWW.BCBSRI.COM

1. Centers for Medicaid & Medicare Services. National Coverage Determination (NCD) for Outpatient Intravenous Insulin Treatment (40.7). 2009; https://www.cms.gov/medicare-coverage- database/details/ncd-details.aspx?NCDId=334. Accessed December 13, 2024.
2. ElSayed NA, McCoy RG, Aleppo G, et al. 9. Pharmacologic Approaches to Glycemic Treatment: Standards of Care in Diabetes-2025. Diabetes Care. Jan 01 2025; 48(Supplement_1): S181-S206. PMID 39651989
3. 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. PMID 19446964
4. 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): 515-8. PMID 8102666
5. Aoki TT, Grecu EO, Arcangeli MA. Chronic intermittent intravenous insulin therapy corrects orthostatic hypotension of diabetes. Am J Med. Dec 1995; 99(6): 683-4. PMID 7503093
6. 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): 1260-5.PMID 8612440
7. 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. Oct 2010; 59(10): 1429-34. PMID 20189608
8. 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): 1491-5. PMID 11092517

9. 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.PMID 35963508

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   This medical policy is made available to you for informational purposes only. It is not a guarantee of payment or a substitute for your medical judgment in the treatment of your patients. Benefits and eligibility are determined by the member's subscriber agreement or member certificate and/or the employer agreement, and those documents will supersede the provisions of this medical policy. For information on member-specific benefits, call the provider call center. If you provide services to a member which are determined to not be medically necessary (or in some cases medically necessary services which are non-covered benefits), you may not charge the member for the services unless you have informed the member and they have agreed in writing in advance to continue with the treatment at their own expense. Please refer to your participation agreement(s) for the applicable provisions. This policy is current at the time of publication; however, medical practices, technology, and knowledge are constantly changing. BCBSRI reserves the right to review and revise this policy for any reason and at any time, with or without notice. Blue Cross & Blue Shield of Rhode Island is an independent licensee of the Blue Cross and Blue Shield Association. CLICK THE ENVELOPE ICON BELOW TO SUBMIT COMMENTS