Friday, April 27, 2012

Diabetes Cancer risk and " Drugs of Interest "

Diabetes medications that may be associated with cancer risk features 2 medications groups as "drugs of interest " , sulfonylureas and Insulin.

I have attached a few abstracts , copied from Medscape articles,  and high lighted statements of interest to our discussion today. Most of the articles I have reviewed seem to agree that there is some slight increase in cancer risk for people with Type 2 Diabetes.
 Metformin ( glucophage ) is generally associated with lower risk of cancer but attaching the higher risk of cancer label to other diabetes medications such as Insulin and Sulfonylureas remains in the category of  "drugs of interest ".  There seem to be a lot of " may be associated " in the discussions.
 Research into this area is  an ongoing process and we may have a definite answer in the future.

What should we do while waiting for a definite answer?  
Some of the newer medications , GLP-1 agonist and DPP-4 inhibitors ,  have given us tools that will allow full retirement of sulfonylurea medications and delay or even prevent the need for insulin in many people with Type 2 Diabetes.  This does not mean that we should delay moving to insulin quickly when other medications have failed to control blood glucose levels.  The benefits of insulin are much greater than the unproven risk of insulin.

 Please review my Feb 9 and 10 Blogs for more on GLP-1 agonist and DPP-4 inhibitors.

Have fun , be Smart , Ask your doctor specific questions and you will be amazed at the amount of wisdom and knowledge available to you today in your doctors office .

David Calder,MD

Mortality After Incident Cancer in People With and Without Type 2 Diabetes
Impact of metformin on survival
Author Affiliations
  • 1Department of Primary Care and Public Health, School of Medicine, Cardiff University, Cardiff, U.K.
  • 2Global Epidemiology, Pharmatelligence, Cardiff, U.K.
  • 3Diabetes and Metabolism, School of Clinical Sciences, University of Bristol, Bristol, U.K.
  • 4School of Public Health, University of Alberta, Edmonton, Alberta, Canada
OBJECTIVE Type 2 diabetes is associated with an increased risk of several types of cancer and with reduced survival after cancer diagnosis. We examined the hypotheses that survival after a diagnosis of solid-tumor cancer is reduced in those with diabetes when compared with those without diabetes, and that treatment with metformin influences survival after cancer diagnosis.
RESEARCH DESIGN AND METHODS Data were obtained from >350 U.K. primary care practices in a retrospective cohort study. All individuals with or without diabetes who developed a first tumor after January 1990 were identified and records were followed to December 2009. Diabetes was further stratified by treatment regimen. Cox proportional hazards models were used to compare all-cause mortality from all cancers and from specific cancers.
RESULTS Of 112,408 eligible individuals, 8,392 (7.5%) had type 2 diabetes. Cancer mortality was increased in those with diabetes, compared with those without (hazard ratio 1.09 [95% CI 1.06–1.13]). Mortality was increased in those with breast (1.32 [1.17–1.49]) and prostate cancer (1.19 [1.08–1.31]) but decreased in lung cancer (0.84 [0.77–0.92]). When analyzed by diabetes therapy, mortality was increased relative to nondiabetes in those on monotherapy with sulfonylureas (1.13 [1.05–1.21]) or insulin (1.13 [1.01–1.27]) but reduced in those on metformin monotherapy (0.85 [0.78–0.93]).
CONCLUSIONS This study confirmed that type 2 diabetes was associated with poorer prognosis after incident cancer, but that the association varied according to diabetes therapy and cancer site. Metformin was associated with survival benefit both in comparison with other treatments for diabetes and in comparison with a nondiabetic population.
Metformin Associated With Lower Cancer Risk
Allan S. Brett, MD
Posted: 03/26/2012; Journal Watch © 2012 Massachusetts Medical Society

  • Abstract and Introduction
  • Comment
Abstract and Introduction
Compared with sulfonylurea users, metformin users had a 10% lower incidence of cancer.
During the past decade, observational studies have suggested associations between cancer and type 2 diabetes (or insulin therapy). Although several plausible mechanisms exist (e.g., cancer cells express insulin receptors that when activated could promote cell proliferation in type 2 diabetic patients with hyperinsulinemia), the association remains controversial (CA Cancer J Clin 2010; 60:207). In some studies, metformin has been associated with decreased cancer risk.
In a population-based retrospective study, Dutch researchers recorded the incidence of cancer in 85,000 type 2 diabetic patients who initiated metformin or sulfonylurea monotherapy. During up to 10 years of follow-up, metformin users were less likely to receive cancer diagnoses than sulfonylurea users (hazard ratio, 0.9; 95% confidence interval, 0.88–0.91) after adjustment for age, sex, and several other variables. This 10% reduction was modest in relative terms but highly statistically significant. Metformin-associated lower risks were noted for cancers of the esophagus, stomach, colon, liver, pancreas, lung, breast, and prostate.

Section 1 of 2

Insulin Analogues and Cancer Risk: Cause for Concern or Cause Célèbre?

M. Pollak; D. Russell-Jones
Posted: 03/31/2010; Int J Clin Pract. 2010;65(5):628-636. © 2010 Blackwell Publishing

Abstract and Introduction


People with diabetes, particularly those with type 2 diabetes, may be at an increased risk of cancer. Furthermore, their cancer risk may be modified by treatment choices. In this respect, metformin may be protective, whereas insulin and insulin analogues can function as growth factors and therefore have theoretical potential to promote tumour proliferation. Analogues causing inappropriate prolonged stimulation of the insulin receptor, or excess stimulation of the IGF-1 receptor, are the most likely to show mitogenic properties in laboratory studies. Some recent epidemiological studies appear to be consistent with these experimental findings, suggesting that there could be different relative risks for cancer associated with different insulins, although these studies have attracted some methodological criticism. However, it is biologically plausible that hormonal factors that influence neoplasia could begin to manifest their effects in surprisingly short timescales (within 2 years) and hence these epidemiological studies justify further research. Even if future research were to document an increase in cancer risk among insulin users, this would be unlikely to significantly diminish the favourable benefit-risk ratio for patients requiring insulin therapy. There is a need for further population studies and for the development of new laboratory models that are more sophisticated than previous experimental methods employed to assess potential tumour growth-promoting properties of insulins.

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Your comments and questions are appreciated. David Calder,MD