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Rich66 · 06-05-2009, 12:08 PM


REFERENCE: Toleration of Metformin in non-diabetic patients.


1: Arch Physiol Biochem. 2009 May;115(2):86-96.: Obesity related hyperinsulinaemia and hyperglycaemia and cancer development.

Becker S, Dossus L, Kaaks R.
Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Excess body weight in combination with physical inactivity is a major determinant for the development of insulin resistance with associated hyperglycaemia and hyperinsulinaemia and further leads to tumour development. Several prospective epidemiological studies have shown a direct association between excess weight and common malignancies, such as colon, breast (post-menopausal), endometrial, gallbladder, pancreatic, kidney and oesophageal cancers, but also less frequent malignancies, such as leukaemia, multiple myeloma and non-Hodgkin lymphoma. Insulin resistance and hyperinsulinaemia are certainly key biological mechanisms underlying the relationship between adiposity and tumour development. The anti-diabetic drug, metformin, in addition to reduction of insulin resistance has also shown anti-tumour properties, and is increasingly being considered as a drug to prevent and treat obesity-related cancers. Several biological pathways have been involved in the association between excess body weight, insulin resistance and cancer, such as chronic low-grade inflammation, glucose toxicity, AGE product metabolism and the adenosine monophosphate kinase pathway.
PMID: 19485704 [PubMed - in process

Arch Pediatr Adolesc Med. 2010 Feb;164(2):116-23.
Metformin Extended Release Treatment of Adolescent Obesity: A 48-Week Randomized, Double-Blind, Placebo-Controlled Trial With 48-Week Follow-up.

Glaser Pediatric Research Network Obesity Study Group.
Division of Pediatric Endocrinology and Diabetes, Stanford University and the Lucile Packard Children's Hospital at Stanford, G-313 Medical Center, Stanford, CA 94305-5208. dwilson@stanford.edu.
BACKGROUND: Metformin has been proffered as a therapy for adolescent obesity, although long-term controlled studies have not been reported. OBJECTIVE: To test the hypothesis that 48 weeks of daily metformin hydrochloride extended release (XR) therapy will reduce body mass index (BMI) in obese adolescents, as compared with placebo. DESIGN: Multicenter, randomized, double-blind, placebo-controlled clinical trial. SETTING: The 6 centers of the Glaser Pediatric Research Network from October 2003 to August 2007. PARTICIPANTS: Obese (BMI>/=95th percentile) adolescents (aged 13-18 years) were randomly assigned to the intervention (n = 39) or placebo groups. Intervention Following a 1-month run-in period, subjects following a lifestyle intervention program were randomized 1:1 to 48 weeks' treatment with metformin hydrochloride XR, 2000 mg once daily, or an identical placebo. Subjects were monitored for an additional 48 weeks. Main Outcome Measure Change in BMI, adjusted for site, sex, race, ethnicity, and age and metformin vs placebo. RESULTS: After 48 weeks, mean (SE) adjusted BMI increased 0.2 (0.5) in the placebo group and decreased 0.9 (0.5) in the metformin XR group (P = .03). This difference persisted for 12 to 24 weeks after cessation of treatment. No significant effects of metformin on body composition, abdominal fat, or insulin indices were observed. CONCLUSION: Metformin XR caused a small but statistically significant decrease in BMI when added to a lifestyle intervention program. Trial Registration clinicaltrials.gov Identifiers: NCT00209482 and NCT00120146.

PMID: 20124139 [PubMed - in process]

06-05-2009, 12:08 PM	#6
Rich66 Senior Member Join Date: Feb 2008 Location: South East Wisconsin Posts: 3,431	REFERENCE: Toleration of Metformin in non-diabetic patients. 1: Arch Physiol Biochem. 2009 May;115(2):86-96. Obesity related hyperinsulinaemia and hyperglycaemia and cancer development. Becker S, Dossus L, Kaaks R. Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany. Excess body weight in combination with physical inactivity is a major determinant for the development of insulin resistance with associated hyperglycaemia and hyperinsulinaemia and further leads to tumour development. Several prospective epidemiological studies have shown a direct association between excess weight and common malignancies, such as colon, breast (post-menopausal), endometrial, gallbladder, pancreatic, kidney and oesophageal cancers, but also less frequent malignancies, such as leukaemia, multiple myeloma and non-Hodgkin lymphoma. Insulin resistance and hyperinsulinaemia are certainly key biological mechanisms underlying the relationship between adiposity and tumour development. The anti-diabetic drug, metformin, in addition to reduction of insulin resistance has also shown anti-tumour properties, and is increasingly being considered as a drug to prevent and treat obesity-related cancers. Several biological pathways have been involved in the association between excess body weight, insulin resistance and cancer, such as chronic low-grade inflammation, glucose toxicity, AGE product metabolism and the adenosine monophosphate kinase pathway. PMID: 19485704 [PubMed - in process Arch Pediatr Adolesc Med. 2010 Feb;164(2):116-23. Metformin Extended Release Treatment of Adolescent Obesity: A 48-Week Randomized, Double-Blind, Placebo-Controlled Trial With 48-Week Follow-up. Glaser Pediatric Research Network Obesity Study Group. Division of Pediatric Endocrinology and Diabetes, Stanford University and the Lucile Packard Children's Hospital at Stanford, G-313 Medical Center, Stanford, CA 94305-5208. dwilson@stanford.edu. BACKGROUND: Metformin has been proffered as a therapy for adolescent obesity, although long-term controlled studies have not been reported. OBJECTIVE: To test the hypothesis that 48 weeks of daily metformin hydrochloride extended release (XR) therapy will reduce body mass index (BMI) in obese adolescents, as compared with placebo. DESIGN: Multicenter, randomized, double-blind, placebo-controlled clinical trial. SETTING: The 6 centers of the Glaser Pediatric Research Network from October 2003 to August 2007. PARTICIPANTS: Obese (BMI>/=95th percentile) adolescents (aged 13-18 years) were randomly assigned to the intervention (n = 39) or placebo groups. Intervention Following a 1-month run-in period, subjects following a lifestyle intervention program were randomized 1:1 to 48 weeks' treatment with metformin hydrochloride XR, 2000 mg once daily, or an identical placebo. Subjects were monitored for an additional 48 weeks. Main Outcome Measure Change in BMI, adjusted for site, sex, race, ethnicity, and age and metformin vs placebo. RESULTS: After 48 weeks, mean (SE) adjusted BMI increased 0.2 (0.5) in the placebo group and decreased 0.9 (0.5) in the metformin XR group (P = .03). This difference persisted for 12 to 24 weeks after cessation of treatment. No significant effects of metformin on body composition, abdominal fat, or insulin indices were observed. CONCLUSION: Metformin XR caused a small but statistically significant decrease in BMI when added to a lifestyle intervention program. Trial Registration clinicaltrials.gov Identifiers: NCT00209482 and NCT00120146. PMID: 20124139 [PubMed - in process]