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Rich66 · 12-04-2009, 04:02 PM

http://www.oncologystat.com/news-and..._Study_US.html

Metformin Use Protective Against Cancer Mortality in Prospective Study Elsevier Global Medical News.
2009 Nov 25, D Napoli

Metformin may be protective against cancer-related mortality in type 2 diabetes, according to data from a prospective study of over 1,300 patients in the Netherlands. The finding - the first to come from a prospective study - could "further strengthen the position of metformin as preferred initial treatment in patients with type 2 diabetes mellitus," wrote the study authors in an article published online on Nov. 16 ahead of print in Diabetes Care (doi:10.2337/dc09-1380). The authors, led by Dr. Gijs W. Landman of the Isala Clinics in Zwolle, the Netherlands, looked at 1,353 patients who were enrolled in the Zwolle Outpatient Diabetes Project Integrating Available Care (ZODIAC) study. That study, begun in 1998, aimed to assess patients under the care of diabetes specialist nurses in addition to general practitioners. A total of 289 patients in the ZODIAC study used metformin at baseline; 1,064 did not. The average age of all patients was about 68 years, and slightly more than half were women. Among metformin users, the average duration of disease was 4.9 years, compared with 7.1 years in the nonuser group, a non-significant difference. The nonuser group did have significantly lower HbA1c levels, lower body mass index levels, and lower estimated glomerular filtration rates (eGFR), as well as significantly higher rates of use of insulin and sulfonylurea. After a mean follow-up of 9.6 years, there were a total of 122 cancer deaths in the entire cohort. According to the authors, the standardized mortality rate for cancer mortality among all patients was 1.47 (95% CI 1.22-1.76). However, adjusted for 13 variables including smoking, age, sex, diabetes duration and pertinent lab values, metformin patients' hazard ratio fell to 0.43, compared with nonusers (95% CI 0.23-0.80). Furthermore, "The hazard [ratio] for cancer mortality decreased by 42% for every one gram increase in the metformin dosage," wrote the authors. The research study had some limitations. According to the authors, "patients with a very short life expectancy (including patients with active cancer) or insufficient cognitive abilities were excluded" from the original ZODIAC study. In addition, there are no data about nonfatal cancer incidence, nor about cancer history. The authors also pointed out that metformin was a relatively new drug at the ZODIAC study's baseline. "Patients who were taking metformin at the beginning of this study (in 1998) might also be different from patients taking metformin at this moment," they wrote. "If there is an association between cancer mortality and metformin use, a long-term follow-up is needed, because cancer takes a long time to develop and it takes time before patients die from cancer," they added. According to Dr. Landman, the study authors - all from the Netherlands - had no personal disclosures to report, nor did the study receive any outside funding or support.

Metformin and Letrozole seem compatible at some level in non-cancer setting:

Hum Reprod. 2006 Jun;21(6):1432-5. Epub 2006 Feb 14.
Efficacy of combined metformin-letrozole in comparison with metformin-clomiphene citrate in clomiphene-resistant infertile women with polycystic ovarian disease.

Sohrabvand F, Ansari Sh, Bagheri M.
Department of Infertility & IVF, Vali-e-Asr Hospital, Tehran University of Medical Sciences, Tehran, Iran. fsohrabvand@yahoo.com
BACKGROUND: Adding metformin to clomiphene citrate in clomiphene-resistant polycystic ovary syndrome (PCOS) patients increases ovulatory response. However, because of anti-estrogenic effects of clomiphene it may be associated with lower pregnancy rate, offsetting the ovulation rate benefit. Letrozole is an aromatase inhibitor which induces ovulation without anti-estrogenic effects. METHODS: Infertile women with PCOS were randomly divided into metformin-letrozole (29 patients) and metformin-clomiphene groups (30 patients). After an initial 6-8 weeks of metformin, they received either letrozole (2.5 mg) or clomiphene (100 mg) from day 3-7 of their menstrual cycle. Estradiol (E2) levels, number of follicles, pregnancy rates and endometrial thickness were measured on the day of HCG administration. RESULTS: Mean total E2 and E2 per mature follicle were significantly higher in clomiphene group without a difference in mean number of mature follicles >18 mm and ovulation rate. Endometrial thickness was significantly higher in letrozole group. The pregnancy rate in letrozole group (10 patients, 34.50%) as compared with clomiphene group (5 patients, 16.67%) did not show significant difference, whereas full-term pregnancies were higher in letrozole group [10 patients (34.50%) versus 3 patients (10%)]. CONCLUSION: In clomiphene-resistant PCOS patients, the combination of letrozole and metformin leads to higher full-term pregnancies.

PMID: 16478764 [PubMed - indexed for MEDLINE]

12-04-2009, 04:02 PM	#24
Rich66 Senior Member Join Date: Feb 2008 Location: South East Wisconsin Posts: 3,431	Re: Common Diabetes Drug May 'Revolutionize' Cancer Therapies: Unexpected T-cell Brea http://www.oncologystat.com/news-and..._Study_US.html Metformin Use Protective Against Cancer Mortality in Prospective Study Elsevier Global Medical News. 2009 Nov 25, D Napoli Metformin may be protective against cancer-related mortality in type 2 diabetes, according to data from a prospective study of over 1,300 patients in the Netherlands. The finding - the first to come from a prospective study - could "further strengthen the position of metformin as preferred initial treatment in patients with type 2 diabetes mellitus," wrote the study authors in an article published online on Nov. 16 ahead of print in Diabetes Care (doi:10.2337/dc09-1380). The authors, led by Dr. Gijs W. Landman of the Isala Clinics in Zwolle, the Netherlands, looked at 1,353 patients who were enrolled in the Zwolle Outpatient Diabetes Project Integrating Available Care (ZODIAC) study. That study, begun in 1998, aimed to assess patients under the care of diabetes specialist nurses in addition to general practitioners. A total of 289 patients in the ZODIAC study used metformin at baseline; 1,064 did not. The average age of all patients was about 68 years, and slightly more than half were women. Among metformin users, the average duration of disease was 4.9 years, compared with 7.1 years in the nonuser group, a non-significant difference. The nonuser group did have significantly lower HbA1c levels, lower body mass index levels, and lower estimated glomerular filtration rates (eGFR), as well as significantly higher rates of use of insulin and sulfonylurea. After a mean follow-up of 9.6 years, there were a total of 122 cancer deaths in the entire cohort. According to the authors, the standardized mortality rate for cancer mortality among all patients was 1.47 (95% CI 1.22-1.76). However, adjusted for 13 variables including smoking, age, sex, diabetes duration and pertinent lab values, metformin patients' hazard ratio fell to 0.43, compared with nonusers (95% CI 0.23-0.80). Furthermore, "The hazard [ratio] for cancer mortality decreased by 42% for every one gram increase in the metformin dosage," wrote the authors. The research study had some limitations. According to the authors, "patients with a very short life expectancy (including patients with active cancer) or insufficient cognitive abilities were excluded" from the original ZODIAC study. In addition, there are no data about nonfatal cancer incidence, nor about cancer history. The authors also pointed out that metformin was a relatively new drug at the ZODIAC study's baseline. "Patients who were taking metformin at the beginning of this study (in 1998) might also be different from patients taking metformin at this moment," they wrote. "If there is an association between cancer mortality and metformin use, a long-term follow-up is needed, because cancer takes a long time to develop and it takes time before patients die from cancer," they added. According to Dr. Landman, the study authors - all from the Netherlands - had no personal disclosures to report, nor did the study receive any outside funding or support. Metformin and Letrozole seem compatible at some level in non-cancer setting: Hum Reprod. 2006 Jun;21(6):1432-5. Epub 2006 Feb 14. Efficacy of combined metformin-letrozole in comparison with metformin-clomiphene citrate in clomiphene-resistant infertile women with polycystic ovarian disease. Sohrabvand F, Ansari Sh, Bagheri M. Department of Infertility & IVF, Vali-e-Asr Hospital, Tehran University of Medical Sciences, Tehran, Iran. fsohrabvand@yahoo.com BACKGROUND: Adding metformin to clomiphene citrate in clomiphene-resistant polycystic ovary syndrome (PCOS) patients increases ovulatory response. However, because of anti-estrogenic effects of clomiphene it may be associated with lower pregnancy rate, offsetting the ovulation rate benefit. Letrozole is an aromatase inhibitor which induces ovulation without anti-estrogenic effects. METHODS: Infertile women with PCOS were randomly divided into metformin-letrozole (29 patients) and metformin-clomiphene groups (30 patients). After an initial 6-8 weeks of metformin, they received either letrozole (2.5 mg) or clomiphene (100 mg) from day 3-7 of their menstrual cycle. Estradiol (E2) levels, number of follicles, pregnancy rates and endometrial thickness were measured on the day of HCG administration. RESULTS: Mean total E2 and E2 per mature follicle were significantly higher in clomiphene group without a difference in mean number of mature follicles >18 mm and ovulation rate. Endometrial thickness was significantly higher in letrozole group. The pregnancy rate in letrozole group (10 patients, 34.50%) as compared with clomiphene group (5 patients, 16.67%) did not show significant difference, whereas full-term pregnancies were higher in letrozole group [10 patients (34.50%) versus 3 patients (10%)]. CONCLUSION: In clomiphene-resistant PCOS patients, the combination of letrozole and metformin leads to higher full-term pregnancies. PMID: 16478764 [PubMed - indexed for MEDLINE] __________________ Mom's treatment history (link)