Insulin Potentiation Therapy - CAM 20172

Insulin potentiation therapy (IPT) uses insulin as an adjunctive agent to potentiate the effects of pharmacologic therapy in the treatment of cancer, infectious diseases, chronic degenerative disorders, and many other conditions.

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 in Mexico by Donato Perez Garcia, Sr., MD. 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 9 weeks.1

Related Policy
20143 Chronic Intermittent Intravenous Insulin Therapy

Insulin potentiation therapy (IPT) is considered INVESTIGATIONAL.     

Policy Guidelines
There is no specific CPT code describing insulin potentiation therapy (IPT). The following series of CPT codes and HCPCS J codes are used to describe the various components of IPT. Some codes, such as the code for glucose testing, may be used more than once during a single session of IPT:

CPT codes
82948: Glucose; blood, reagent strip
96365: Intravenous infusion, for therapy, prophylaxis, or diagnosis (specify substance or drug); initial, up to 1 hour
96366: each additional hour (List separately in addition to code for primary procedure.)
99070: Supplies and materials provided by the physician
99211: Office or other outpatient visit (established patient)

J codes
J1817: Insulin for administration through DME (i.e., insulin pump) per 50 units
J7030: Infusion, normal saline solution, 1000 cc
J7040: Infusion, normal saline solution, sterile (500 cc)
J7050: Infusion, normal saline solution, 250 cc

Benefit Application
BlueCard/National Account Issues
State or federal mandates (e.g., FEP) may dictate that all U.S. Food and Drug Administration (FDA)-approved devices, drugs, or biologics may not be considered investigational, and thus, these devises may be assessed only on the basis of their medical necessity.

Insulin potentiation therapy is typically offered in specialized clinics. Many locations throughout the United States offer insulin potentiation therapy.

Literature Review
Insulin potentiation therapy (IPT) has been explored in a minority of physician practices since the 1930s.2,3 However, there is only one randomized controlled trial (RCT) on the effects of IPT 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. Also, it appears that this is not an area of active research.

The only RCT on IPT was published by Lasalvia-Prisco and colleagues, in 2004, who reported on 30 patients (3 groups of 10) randomly assigned to receive two 21-day courses of insulin with methotrexate (IPT), methotrexate alone, or insulin alone.5 Patients had metastatic breast cancer that was resistant to fluorouracil, doxorubicin, and cyclophosphamide, as well as hormone therapy (if they had a positive estrogen receptor status). The primary outcome assessed at 8 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 9 stable diseases and 1 progressive disease versus 3 stable and 7 progressive diseases in the methotrexate-only group and 2 stable and 8 progressive diseases in the insulin-only group (distribution of results: p < 0.01, Chi-squared test). In addition, the increase in tumor size was significantly lower for the IPT group compared to the methotrexate-only and the insulin-only treatment groups (p < 0.001). Toxicities were low in both the IPT group (only 1 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 insulin. While this study may suggest that 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.

A 2006 publication described preclinical safety and antitumor efficacy of insulin combined with irradiation.6 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.7

No trials investigating the treatment of fibromyalgia, chronic fatigue syndrome, arthritis, or infections have been published or are currently recruiting subjects.8

Much of the information about insulin potentiation therapy (IPT) comes from short-term anecdotal reports. A single randomized controlled trial suggested that tumor progression can be affected by IPT at 8 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; IPT remains investigational.

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."1


  1. American Cancer Society. Insulin Potentiation Therapy. 

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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

Coding Section






See Policy Guidelines

ICD-9 Procedure



ICD-9 Diagnosis


Investigational for all relevant diagnoses



See Policy Guidelines

ICD-10-CM (effective 10/01/15)


Investigational for all relevant diagnoses

ICD-10-PCS (effective 10/01/15)


ICD-10-PCS codes are only used for inpatient services.


3E030VG, 3E033VG,
3E040VG,  3E043VG,
3E050VG, 3E053VG,
3E060VG, 3E063VG

Administration, physiological systems and anatomical regions, introduction, hormone, insulin, codes for peripheral and central vein or artery and open or percutaneous approach 

Type of Service



Place of Service

Physician's office or clinic


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.

This medical policy was developed through consideration of peer-reviewed medical literature generally recognized by the relevant medical community, U.S. FDA approval status, nationally accepted standards of medical practice and accepted standards of medical practice in this community, Blue Cross Blue Shield Association technology assessment program (TEC) and other non-affiliated technology evaluation centers, reference to federal regulations, other plan medical policies, and accredited national guidelines.

"Current Procedural Terminology © American Medical Association. All Rights Reserved" 

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