BlueCross and BlueShield of Montana Medical Policy/Codes
Insulin Potentiation Therapy
Chapter: Medicine: Treatments
Current Effective Date: July 18, 2013
Original Effective Date: October 20, 2010
Publish Date: July 18, 2013
Revised Dates: No longer scheduled for review: April 26, 2013

The observation that some cancer cells may express a greater number of insulin receptors has been the basis of the hypothesis for insulin potentiation therapy (IPT).  The physiologic effects of insulin in IPT are thought to increase the permeability of cell membranes and facilitate increased intracellular absorption of pharmacologic agents.  Theoretically, the increased absorption of a pharmacologic agent results in higher intracellular drug concentrations; lower dosage requirements could then reduce toxicity and adverse side effects.  IPT was developed in the 1930s by a physician in Mexico.  It is primarily used in the treatment of cancer, for which increasing the intracellular concentration and cytotoxic effects of chemotherapy agents while decreasing the adverse effects is thought to increase antitumoral activity and patient tolerance to treatment. There have been proponents of using IPT for other conditions as well, such as infectious diseases, chronic degenerative disorders, chronic fatigue syndrome and fibromyalgia.

For cancer patients, a hypoglycemic state is induced in the minutes prior to infusion with standard chemotherapy delivered at sub-therapeutic doses.  During this time, the patient may experience moderate to severe symptoms of hypoglycemia, including sweating, lightheadedness, and nausea.  The patient is infused with glucose solution after chemotherapy is initiated and hypoglycemia has been achieved.  A typical treatment regimen consists of biweekly sessions for up to nine weeks.


Each benefit plan, summary plan description or contract defines which services are covered, which services are excluded, and which services are subject to dollar caps or other limitations, conditions or exclusions.  Members and their providers have the responsibility for consulting the member's benefit plan, summary plan description or contract to determine if there are any exclusions or other benefit limitations applicable to this service or supply.  If there is a discrepancy between a Medical Policy and a member's benefit plan, summary plan description or contract, the benefit plan, summary plan description or contract will govern.


Blue Cross and Blue Shield of Montana (BCBSMT) considers insulin potentiation therapy (IPT) experimental, investigational and unproven.


Insulin potentiation therapy (IPT) has been explored in a minority of physician practices since the 1930s.  However, there is only one randomized controlled trial on the effects of insulin potentiation therapy in metastatic breast cancer.  No studies have demonstrated that IPT is safe or effective in improving long-term health outcomes over standard or conventional pharmacologic treatment for any disease state.  In addition, it appears this is not an area of active research.

The only randomized controlled clinical trial (RCT) on IPT was published in 2004 by Lasalvia-Prisco and colleagues, who reported on 30 patients (three groups of 10) randomized to receive two 21-day courses of insulin with methotrexate (IPT), methotrexate alone, or insulin alone.  Patients had metastatic breast cancer that was resistant to fluorouracil, adriamycin, and cyclophosphamide as well as hormone therapy (if they had a positive estrogen receptor status).  The primary outcome assessed at eight weeks after initiation of treatment was tumor response using the response evaluation criteria in solid tumors (RECIST) system.  The authors reported finding the RECIST status in the IPT group was nine stable diseases and one progressive disease versus three stable diseases and seven progressive in the methotrexate-only group, and two stable diseases and eight progressive in the insulin-only group (distribution of results = p<0.01, Chi-squared test).  In addition, the IPT group had significantly lower increases in tumor size than the methotrexate-only and the insulin-only treatment groups (p<0.001).  Toxicities were low in both the IPT group (only one World Health Organization [WHO] grade 1 mucositis) and the methotrexate-only group (WHO grade 1-2) as the individual methotrexate dosage of 2.5 mg/m² used in the study was lower than optimal.  The authors suggest that these findings support the theory that the antitumoral effects of methotrexate were potentiated by the use of insulin.  While this study may suggest insulin enhances some biochemical event with the administration of chemotherapy in the short term, it does not report on any long-term effects or health outcomes.  Therefore, further studies are needed to demonstrate any improvements in health outcomes with the use of insulin potentiation therapy.

2011 Update

Literature Review

A 2006 publication described preclinical safety and antitumor efficacy of insulin combined with irradiation.  Using the intestinal crypt regeneration assay, a delay in regrowth was noted when insulin therapy was combined with radiation.  The need for larger preclinical assays was noted by the authors as a next step, before studies of possible clinical utility are conducted.  Additional basic science research is currently being conducted on the role of insulin growth factors in cancer.

A search of the US Clinical Trials Registry revealed that no trials investigating the treatment of fibromyalgia, chronic fatigue syndrome, arthritis, or infections have been published or are currently recruiting subjects.

Practice Guidelines and Position Statements

In 2008, the American Cancer Society released the following statement:  “Despite supporters' claims that insulin potentiation therapy has been well researched, no scientific studies that show safety and effectiveness have been published in available peer-reviewed journals.  These claims cannot be verified.  There are also concerns about using lower doses of chemotherapy drugs.  When chemotherapy drugs are tested in clinical trials, their effects are carefully monitored to learn which dose will best balance the need to kill cancer cells with the goal of keeping side effects at a tolerable level.  There is no evidence that chemotherapy at a fraction of the recommended and tested dose can produce the same effect as the full dose if used with insulin.”


Much of the information about IPT comes from short-term anecdotal reports.  A single randomized controlled trial suggested that tumor progression can be affected by IPT at eight weeks.  No survival or longer term data are available.  Therefore, further studies are needed to demonstrate whether improvements in health outcomes occur with the use of insulin potentiation therapy; the coverage position remains unchanged.


Disclaimer for coding information on Medical Policies

Procedure and diagnosis codes on Medical Policy documents are included only as a general reference tool for each policy.  They may not be all-inclusive.

The presence or absence of procedure, service, supply, device or diagnosis codes in a Medical Policy document has no relevance for determination of benefit coverage for members or reimbursement for providers.  Only the written coverage position in a medical policy should be used for such determinations.

Benefit coverage determinations based on written Medical Policy coverage positions must include review of the member’s benefit contract or Summary Plan Description (SPD) for defined coverage vs. non-coverage, benefit exclusions, and benefit limitations such as dollar or duration caps. 

ICD-9 Codes

Experimental, investigational and unproven for all diagnoses.

ICD-10 Codes

Experimental, investigational and unproven for all diagnoses.

Procedural Codes: There are no specific codes for insulin potentiation therapy.
  1. Ayre SG, Perez Garcia y Bellon D, Perez Garcia D Jr.  Insulin potentiation therapy: a new concept in the management of chronic degenerative disease.  Med Hypotheses 1986; 20(2):199-210.
  2. Ayre SG, Perez Garcia y Bellon D, Perez Garcia D, Jr.  Neoadjuvant low-dose chemotherapy with insulin in breast carcinomas.  Eur J Cancer 1990; 26(11-12):1262-3.
  3. Ayre SG, Garcia y Bellon DP, Garcia DP Jr.  Insulin, chemotherapy, and the mechanisms of malignancy: the design and the demise of cancer.  Med Hypotheses 2000; 55(4):330-4.
  4. Lasalvia-Prisco E, Cucchi S, Vazquez J et al.  Insulin-induced enhancement of antitumoral response to methotrexate in breast cancer patients.  Cancer Chemother Pharmacol 2004; 53(3):220-4.
  5. Jordan BF, Beghein N, Crokart N et al.  Preclinical safety and antitumor efficacy of insulin combined with irradiation.  Radiother Oncol 2006; 81(1):112-7.
  6. Browne BC, Crown J, Venkatesan N et al.  Inhibition of IGF1R activity enhances response to trastuzumab in HER-2-positive breast cancer cells.  Ann Oncol 2010; 22(1):68-73.
  7. American Cancer Society.  Insulin Potentiation Therapy.  Available at (accessed 2011 October 20).
  8. US Clinical Trials Registry.  Available at (accessed 2011 October 20).
  9. Insulin Potentiation Therapy – Archived.  Chicago, Illinois: Blue Cross Blue Shield Association Medical Policy Reference Manual (2011 August) Surgery 2.01.72.

April 2010  Medical Policy Physician's Committee (PAC) meeting/approved. 
April 2013 Policy formatting and language revised.  Policy statement unchanged.  Removed codes 82948, 96365, 96366, 99070, 99211, J1817, J7030, J7040, J7050.

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CPT codes, descriptions and material only are copyrighted by the American Medical Association. All Rights Reserved. No fee schedules, basic units, relative values or related listings are included in CPT. The AMA assumes no liability for the data contained herein. Applicable FARS/DFARS Restrictions Apply to Government Use. CPT only © American Medical Association.
Insulin Potentiation Therapy