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Diabetes FAQ

Updated September 7, 2013

Liraglutide (Victoza®) approved by FDA.

This new GLP-1 product has been approved by the FDA as an adjunct to diet and exercise for the treatment of type 2 diabetes.  Like its predecessor, exenatide (Byetta®) this product is associated with significant reductions in A1c and weight loss; the most common side effect is nausea.  There has been some concern by the FDA about a finding of thyroid cancers in rats with liraglutide. The question arises if this applies to the other GLP-1 product which has been on the market for quite some time (Byetta®).
What is a thyroid C-cell cancer? C cells in the thyroid gland are important in the production of calcitonin.  Calcitonin reduces serum calcium by opposing parathyroid hormone which tends to increase calcium levels.  Cancers of the C cells of the thyroid gland are called medullary carcinomas. Most medullary thyroid carcinomas (MTC) are sporadic. However, some are familial as part of the multiple endocrine neoplasia type 2 (MEN2) syndrome.1  The ten year survival rates for all patients with medullary thyroid cancer  (MTC) is estimated at 80-90%.

Click here to see more about GLP-1 and other incretin products.

The FDA Black Box warning for Victoza® is quoted as follows:
“Liraglutide causes thyroid C-cell tumors at clinically relevant exposures in rodents. It is unknown whether Victoza causes thyroid C cell tumors, including medullary thyroid carcinoma (MTC), in humans, as human relevance could not be determined by clinical or nonclinical studies.

Victoza is contraindicated in patients with a personal or family history of MTC or in patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2).”

Liraglutide studies

“A 104-week carcinogenicity study was conducted in male and female CD-1 mice at doses of 0.03, 0.2, 1.0, and 3.0 mg/kg/day liraglutide administered by bolus subcutaneous injection yielding systemic exposures 0.2-, 2-, 10- and 45-times the human exposure, respectively, at the MRHD †of 1.8 mg/day based on plasma AUC comparison. A dose-related increase in benign thyroid C-cell adenomas was seen in the 1.0 and the 3.0 mg/kg/day groups with incidences of 13% and 19% in males and 6% and 20% in females, respectively. C-cell adenomas did not occur in control groups or 0.03 and 0.2 mg/kg/day groups.”

“A 104-week carcinogenicity study was conducted in male and female Sprague Dawley rats at doses of 0.075, 0.25 and 0.75 mg/kg/day liraglutide administered by bolus subcutaneous injection with exposures 0.5-, 2- and 8-times the human exposure, respectively, resulting from the MRHD† based on plasma AUC comparison. A treatment-related increase in benign thyroid C-cell adenomas was seen in males in 0.25 and 0.75 mg/kg/day liraglutide groups with incidences of 12%, 16%, 42%, and 46% and in all female liraglutide-treated groups with incidences of 10%, 27%, 33%, and 56% in 0 (control), 0.075, 0.25, and 0.75 mg/kg/day groups, respectively. A treatment-related increase in malignant thyroid C-cell carcinomas was observed in all male liraglutide-treated groups with incidences of 2%, 8%, 6%, and 14% and in females at 0.25 and 0.75 mg/kg/day with incidences of 0%, 0%, 4%, and 6% in 0 (control), 0.075, 0.25, and 0.75 mg/kg/day groups, respectively. Thyroid C-cell carcinomas are rare findings during carcinogenicity testing in rats.”
† MRHD = Maximal Recommended Human Dose

Exenatide studies

“A 104-week carcinogenicity study was conducted in male and female rats at doses of 18, 70, or 250 mcg/kg/day administered by bolus SC injection. Benign thyroid C-cell adenomas were observed in female rats at all exenatide doses. The incidences in female rats were 8% and 5% in the two control groups and 14%, 11%, and 23% in the low-, medium-, and high-dose groups with systemic exposures of 5, 22, and 130 times, respectively, the human exposure resulting from the maximum recommended dose of 20 mcg/day, based on plasma area under the curve (AUC).”

“In a 104-week carcinogenicity study in mice at doses of 18, 70, or 250 mcg/kg/day administered by bolus SC injection, no evidence of tumors was observed at doses up to 250 mcg/kg/day, a systemic exposure up to 95 times the human exposure resulting from the maximum recommended dose of 20 mcg/day, based on AUC.”

A limited Product Comparison




Injection Frequency

Twice daily*

Once Daily

A1c Reduction (used alone)**

-0.7  to -0.9

-0.8 to -1.1


8% to 44%

7.5% to 36.4%

Thyroid tumors in rats***

Benign thyroid C-cell adenomas were observed in female rats at all exenatide doses.

A treatment-related increase in malignant thyroid C-cell carcinomas was observed in male and female liraglutide-treated rats.

*A once weekly Byetta is being examined by the FDA and may be available soon.
**A1c data based on use without other drugs for diabetes.  Reductions are much more striking when used in combination with other products. Byetta® is FDA approved for monotherapy.
***No human thyroid cancers have been reported associated with either product.

In summary, Byetta® and Victoza® are valuable treatments for type 2 diabetes.  The most common side effect of both is nausea. Both cause a delay in stomach emptying and may interfere with the absorption of medications taken by mouth.  Byetta® is given by injection twice daily. Victoza® is given by injection once daily. Both products have been associated with benign thyroid tumors in RATS. Victoza® has been associated with malignant tumors in RATS at doses equivalent to recommended human doses.  Both products are considered effective and safe; else they would have been removed from the marketplace by the FDA.  At the Diabetes Control Center, we would not use either product in a patient with a history of thyroid cancer or a family history of such. Charles H. Raine, III,M.D.


R Michael Tuttle, MD. Clinical manifestations and staging of medullary thyroid cancer. UpToDate

FDA Product Information Label. VICTOZA (liraglutide (rdna origin) injection) injection, solution

FDA Product Information Label BYETTA (exenatide) injection


Is there a cure for diabetes?

The short answer is NO! At least not yet. Type 2 diabetes is a disease of 2 defects:

  • Insulin resistance
  • Insulin lack.

  • At first, the major defect (in type 2 diabetes) may be insulin resistance. In this case insulin available may be normal or increased, but it isn’t working well. Since working insulin is required for glucose to enter the cells, the result is elevated blood glucose (sugar).  Weight loss, exercise and some medications increase the efficiency of insulin action (decreasing insulin resistance). Nothing currently available completely reverses this defect.

    Later in the course of type 2 diabetes, the cells that produce insulin fail to do so (insulin lack). When this occurs, more aggressive treatment (generally with insulin) is required.

    Charles H. Raine, III, M.D.

    Lap-Band® surgery.

    Marked weight loss from surgery in obese type 2 diabetic patients has resulted in remission of signs of diabetes.  Some call this a “cure”. We think “remission” is a more appropriate term.   An article published in Diabetes Care*, indicated “ Remission of diabetes occurred in 32 (of 50) patients (64%), and major improvement of glucose control occurred in 13 patients (26%); glucose metabolism was unchanged in 5 patients. Surgery is not to be taken lightly. The death rate has been reported (elsewhere) at 0 - 3.3% for Laparoscopic gastric bypass and 0. - 0.7% for Laparoscopic adjustable gastric ban."

    This surgery may increase bone fracture risk according to a report at the 2009 Endocrine Society Meeting in Washington DC June 11,2009. People who have undergone bariatric surgery have a 2-fold chance of experiencing broken bones, especially in their hands and feet when compared with the general population. Ninety percent of the patients had the older gastric bypass surgery. Banded gastroplasty (Lap Band) was performed in some of the remaining 10%. “The long term complications of weight loss surgery are not known” according to the presenting endocrinologist (Dr Elizabeth Haglind, M.D.) of the Mayo clinic. Click here to hear the presentation by Dr Haglind.

    *Health Outcomes of Severely Obese Type 2 Diabetic Subjects 1 Year After Laparoscopic Adjustable Gastric Banding;Diabetes Care 25:358-363, 2002

    Recommendations for the surgical treatment of diabetes are:
    BMI 40 kg/m2 or BMI 35 kg/m2 with significant obesity-related risk factors.
    BMI = Body Mass Index (click here for details)
    Age between 16 and 65 years
    Acceptable operative risks
    Documented failure at non surgical approaches to long-term weight loss
    A psychologically stable patient with realistic expectations
    A well-informed and motivated patient
    Commitment to prolonged lifestyle changes
    Supportive family/social environment
    Commitment to long-term follow-up
    Resolution of alcohol or substance abuse
    Absence of active schizophrenia and untreated severe depression

    Medicare coverage of bariatric surgery (such as lap band) for diabetes. The Centers for Medicare and Medicaid Services (CMS) indicated they would consider type 2 diabetes as one of the illnesses occurring with morbid obesity when determining if bariatric surgery is covered. An individual with a BMI ≥ 35 kg/m2 to be considered morbidly obese. A person 5’ 8” tall weighing 230 pounds would have a BMI of 35 kg/m2 . Click here to calculate your BMI. Medicare will only approve the surgery at designated centers. In South Carolina: Conway Medical Services; Hillcrest Hospital SC; Lexington Medical Center; Medical University of South Carolina; Palmetto Health Baptist; Spartanburg Regional Healthcare System. Click here to go the CMS site.

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    Cinnamon and diabetes.

    There is much ado about the effects of cinnamon on diabetes. I did a Google search and found 159,000 hits for “cinnamon and diabetes”. Is there a positive effect of cinnamon on diabetes? The answer is maybe and no. There are several articles in mainstream journals on the subject, some pro and some con.

    Pro. Patients with type 2 diabetes were given 1, 3 or 6 grams of cinnamon or placebo (sham pill) daily. “After 40 days, all three levels of cinnamon reduced the mean fasting serum glucose (18–29%), triglyceride (23–30%), LDL cholesterol (7–27%), and total cholesterol (12–26%) levels; no significant changes were noted in the placebo groups. Changes in HDL cholesterol were not significant.” Diabetes Care 26: 3215-3218
    My criticisms: 1) Only 10 patient in each group. 2) All patients taking diabetes medications (sulfonylurea indicated), other medication not mentioned. 3) Dietary instruction not mentioned. 4) After 40 days the 6 gm dose reduced fasting blood glucose 69 mg/dl (234 to 165). 5) Short duration, no mention of A1c.

    Con.  A study of  Type 1 diabetes. “Cinnamon is not effective for improving glycemic control in adolescents with type 1 diabetes.” Diabetes Care 30:813-816, 2007
    “A systematic literature search through July 2007 (was) conducted to identify randomized placebo-controlled trials of cinnamon that reported data on A1C, fasting blood glucose (FBG), or lipid parameters”. Results: “Cinnamon does not appear to improve A1C, FBG (fasting blood glucose), or lipid parameters in patients with type 1 or type 2 diabetes. Diabetes Care 31:41-43, 2008.

    Conclusion. Cinnamon is not likely help your diabetes. If so, the effect will be small. It will probably not hurt you.

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    Inhaled insulin.

    The initial inhaled insulin (Exubra®) was removed from the market because it did not sell well. The device needed to use it was also large and cumbersome. There were rare cases of lung cancer in people who had been smokers. Inhaled insulin must be used several times daily, generally at mealtime. A new insulin for inhalation is by Mannkind Corp. and is likely to be better. Studies are promising. The current name is expected to be Afresa®. It has a small, palm sized device and may be on the market in 2009 or 2010. Photo from New York Times. Click for New York Times article.

    Veterans Administration study

    VA study* suggests good control of type 2 diabetes no better than poor control in preventing complications. This study, published in the New England Journal of Medicine states:”Intensive glucose (sugar) control in patients with poorly controlled type 2 diabetes had no significant effect on the rates of major cardiovascular events, death, or microvascular complications.”

    The study involved 1791 military veterans (average age, 60.4 years) who did not have good control of diabetes. About 40% already had heart or blood vessel disease. Half were treated with numerous medications and insulin to get average blood sugar to recommended levels (the “Intensive” group) and the other half had “Standard treatment”. 
    Average blood sugar in the Intensive group was about 151 mg/dl (A1c 6.9%) and in the Standard group about 194 mg/dl (A1c 8.4%).

    *"Glucose Control and Vascular Complications in Veterans with Type 2 Diabetes" Published at www.nejm.org December 17, 2008 (10.1056/NEJMoa0808431)

    My comments:
    High blood sugar takes a long time to cause damage, the study was not long enough to show a difference.
    There are numerous long term studies showing that good control prevents complications (e.g. UKPDS, Steno-2 ,Kumamoto).
    The Intensive group had a lot more severe low blood sugar reactions than the Standard group. Severe low blood sugar can cause heart rhythm problems (and sudden death) in people with heart disease. The VA tends to use cheaper insulins (e.g. NPH, Human Regular and Human pre-mixed insulin) that are known to cause low blood sugar more often with intensive treatment than newer analog insulins (e.g. Lantus®, Levemir®, Apidra®, Novolog®, Humalog®).

    We believe that people with diabetes should strive for the best control possible. The American Diabetes Association and the American Association of Clinical Endocrinologists continue to recommend good control of diabetes.  Each person with diabetes is different, consult your Diabetes Team for your best approach.

    Charles H. Raine, III, M.D.

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    Diabetes increases Risk of Alzheimer's Disease

    People with diabetes have an increased risk of Alzheimer's dementia, but there may be a way of avoiding it. The ACCORD-MIND* study demonstrated increased mental function with a lower A1c.  A 1% higher A1C value was associated with a 1.75-point lower score on memory tests. By comparison, every 1-year increase in age was associated with a 0.7-point decrease in the test score. The study authors state… “This analysis of ~3,000 individuals with established type 2 diabetes demonstrates a clear age adjusted inverse relationship between cognitive function and the degree of chronic hyperglycemia as measured by the A1C level.” The take away is that good control of diabetes has benefits in a number of areas, including memory. We recommend maintaining the A1c as close to normal as SAFELY possible. Click here of explanation of A1c.
    *Memory in Diabetes extension of the Action to Control Cardiovascular Risk in Diabetes. Published in DIABETES CARE, VOLUME 32, NUMBER 2, FEBRUARY 2009.

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