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Mauricio Alvarez Endocrinology Program, Facultad de Medicina y Ciencias de la Salud, Universidad Militar Nueva Granada,Bogotá, Colombia
Endocrinology Department, Hospital Militar Central, Bogotá, Colombia

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Oswaldo Rincón Sierra Endocrinology Department, Hospital Militar Central, Bogotá

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Ginna Saavedra Investigation Department, Epidemiology, Hospital Militar Central, Bogotá, Colombia

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Sergio Moreno Investigation Department, Statistics, Hospital Militar Central, Bogotá, Colombia

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Introduction Vitamin B12 deficiency is a known adverse effect of chronic metformin use, which was first described by Berchtold et al. in 1969 ( 1 ) and has been demonstrated in several studies since then ( 2 , 3 , 4 ). The prevalence of

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Xiuzhen Zhang Department of Endocrinology and Metabolism, Shenzhen People’s hospital, The Second Clinical Medical College, Jinan University, Shenzhen, Guangdong, China

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Dan Xu Department of Endocrinology and Metabolism, Shenzhen People’s hospital, The Second Clinical Medical College, Jinan University, Shenzhen, Guangdong, China

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Ping Xu Department of Endocrinology and Metabolism, Shenzhen People’s hospital, The Second Clinical Medical College, Jinan University, Shenzhen, Guangdong, China

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Shufen Yang Department of Endocrinology and Metabolism, Shenzhen People’s hospital, The Second Clinical Medical College, Jinan University, Shenzhen, Guangdong, China

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Qingmei Zhang Department of Endocrinology and Metabolism, Shenzhen People’s hospital, The Second Clinical Medical College, Jinan University, Shenzhen, Guangdong, China

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Yan Wu Department of Endocrinology and Metabolism, Shenzhen People’s hospital, The Second Clinical Medical College, Jinan University, Shenzhen, Guangdong, China

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Fengyi Yuan Department of Endocrinology and Metabolism, Shenzhen People’s hospital, The Second Clinical Medical College, Jinan University, Shenzhen, Guangdong, China

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complications than constant hyperglycemia ( 12 ). For this reason, novel approaches to flattening glucose fluctuations that will reduce the risk of CVD in T1DM are in dire need. For over five decades, metformin is an oral antihyperglycemic drug that has been

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Jothydev Kesavadev Jothydev’s Diabetes Research Centre, Trivandrum, Kerala, India

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Pradeep Babu Sadasivan Pillai Jothydev’s Diabetes Research Centre, Trivandrum, Kerala, India

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Arun Shankar Jothydev’s Diabetes Research Centre, Trivandrum, Kerala, India

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Gopika Krishnan Jothydev’s Diabetes Research Centre, Trivandrum, Kerala, India

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Sunitha Jothydev Jothydev’s Diabetes Research Centre, Trivandrum, Kerala, India

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require insulin therapy due to inadequate glycemic control with oral agents ( 1 ). Metformin and sulfonylureas (SU) are the most commonly used oral antidiabetic agents. However, SU have a greater tendency to cause hypoglycemia and weight gain and hence

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Giovanni Tulipano Unit of Pharmacology, Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy

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cell function. As to drugs, the effects of the well-known hypoglycemic agent metformin on pituitary cell function will be discussed. Metformin is regarded as an indirect AMPK activator; however, its multiple effects on cell metabolism, cell signalling

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Vita Birzniece School of Medicine, Western Sydney University, New South Wales, Australia
Department of Diabetes and Endocrinology, Blacktown Hospital, New South Wales, Australia
Garvan Institute of Medical Research, New South Wales, Australia
School of Medical Sciences, University of New South Wales, New South Wales, Australia

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Teresa Lam School of Medicine, Western Sydney University, New South Wales, Australia
Department of Diabetes and Endocrinology, Blacktown Hospital, New South Wales, Australia
Department of Diabetes and Endocrinology, Westmead Hospital, New South Wales, Australia

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Mark McLean School of Medicine, Western Sydney University, New South Wales, Australia
Department of Diabetes and Endocrinology, Blacktown Hospital, New South Wales, Australia

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Navneeta Reddy Department of Diabetes and Endocrinology, Blacktown Hospital, New South Wales, Australia

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Haleh Shahidipour School of Medicine, Western Sydney University, New South Wales, Australia
Department of Diabetes and Endocrinology, Blacktown Hospital, New South Wales, Australia

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Amy Hayden School of Medicine, Western Sydney University, New South Wales, Australia
Faculty of Medicine, Health and Human Sciences, Macquarie University, New South Wales, Australia
Crown Princess Mary Cancer Centre, Westmead Hospital, New South Wales, Australia

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Howard Gurney Crown Princess Mary Cancer Centre, Westmead Hospital, New South Wales, Australia

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Glenn Stone School of Computing, Engineering and Mathematics, Western Sydney University, New South Wales, Australia

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Rikke Hjortebjerg Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
Endocrine Research Unit, Department of Endocrinology, Odense University Hospital & Department of Clinical Research, Faculty of Health, University of Southern Denmark, Odense, Denmark
Steno Diabetes Center Odense, Odense University Hospital & Department of Clinical Research, Faculty of Health, University of Southern Denmark, Odense, Denmark

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Jan Frystyk Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
Endocrine Research Unit, Department of Endocrinology, Odense University Hospital & Department of Clinical Research, Faculty of Health, University of Southern Denmark, Odense, Denmark

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-diabetic drug metformin may slow cancer progression and improve survival in prostate cancer patients ( 7 , 8 , 9 ). Diabetic patients treated with metformin have a significantly reduced risk of cancer, with meta-analysis reporting metformin to be associated

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Metin Guclu Health Sciences University, Bursa Yuksek Ihtisas Education and Training Hospital, Department of Endocrinology and Metabolism, Bursa, Turkey

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Sinem Kiyici Health Sciences University, Bursa Yuksek Ihtisas Education and Training Hospital, Department of Endocrinology and Metabolism, Bursa, Turkey

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Zulfiye Gul Department of Pharmacology, Uludag University Medical Faculty, Bursa, Turkey

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Sinan Cavun Department of Pharmacology, Uludag University Medical Faculty, Bursa, Turkey

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from pre-screened patients with type 2 diabetes mellitus from an Endocrinology outpatient clinic of a tertiary referral center. Thirty-eight diabetic patients, who were using metformin with and without the other antihyperglycemic drugs on a stable dose

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Thozhukat Sathyapalan Department of Academic Diabetes, Endocrinology and Metabolism, Hull York Medical School, University of Hull, Hull, UK

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Anne-Marie Coady Department of Obstetric Ultrasound, Hull and East Yorkshire Women’s and Children’s Hospital, Hull, UK

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Eric S Kilpatrick Department of Clinical Biochemistry, Sidra Medical and Research Center, Doha, Qatar

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Stephen L Atkin Department of Medicine, Weill Cornell Medical College, Doha, Qatar

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, 37 patients (19 patients from the atorvastatin group and 18 patients from the placebo group) who completed the study were given metformin 500 mg three times daily for 3 months ( 10 ). Clinical and biochemical assessments were performed at baseline, at

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Gunjan Garg Departments of Endocrinology, Obstetrics and Gynecology, Biostatics

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Garima Kachhawa Departments of Endocrinology, Obstetrics and Gynecology, Biostatics

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Rekha Ramot Departments of Endocrinology, Obstetrics and Gynecology, Biostatics

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Rajesh Khadgawat Departments of Endocrinology, Obstetrics and Gynecology, Biostatics

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Nikhil Tandon Departments of Endocrinology, Obstetrics and Gynecology, Biostatics

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V Sreenivas Departments of Endocrinology, Obstetrics and Gynecology, Biostatics

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Alka Kriplani Departments of Endocrinology, Obstetrics and Gynecology, Biostatics

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N Gupta Departments of Endocrinology, Obstetrics and Gynecology, Biostatics

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) . Exclusion criteria Subjects who were currently receiving or had received vitamin D supplementation or treatment for PCOS (metformin, spironolactone, oral contraceptives, or any other drugs) in the last 6 months were excluded from the study. Similarly

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Mohamed Asrih Service of Endocrinology, Diabetes, Nutrition and Patient Therapeutic Education, Geneva University Hospitals, Geneva, Switzerland

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Flore Sinturel Thoracic and Endocrine Surgery Division, Department of Surgery, Geneva University Hospitals (HUG), Geneva, Switzerland
Department of Cell Physiology and Metabolism, Faculty of Medicine, University of Geneva, Geneva, Switzerland
Diabetes Center, Faculty of Medicine, University of Geneva, Geneva, Switzerland

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Richard Dubos Department and Division of Primary Care Medicine, Geneva University Hospitals (HUG), Geneva, Switzerland

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Idris Guessous Department and Division of Primary Care Medicine, Geneva University Hospitals (HUG), Geneva, Switzerland

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Zoltan Pataky Service of Endocrinology, Diabetes, Nutrition and Patient Therapeutic Education, Geneva University Hospitals, Geneva, Switzerland
Diabetes Center, Faculty of Medicine, University of Geneva, Geneva, Switzerland

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Charna Dibner Thoracic and Endocrine Surgery Division, Department of Surgery, Geneva University Hospitals (HUG), Geneva, Switzerland
Department of Cell Physiology and Metabolism, Faculty of Medicine, University of Geneva, Geneva, Switzerland
Diabetes Center, Faculty of Medicine, University of Geneva, Geneva, Switzerland

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François R Jornayvaz Service of Endocrinology, Diabetes, Nutrition and Patient Therapeutic Education, Geneva University Hospitals, Geneva, Switzerland
Department of Cell Physiology and Metabolism, Faculty of Medicine, University of Geneva, Geneva, Switzerland
Diabetes Center, Faculty of Medicine, University of Geneva, Geneva, Switzerland

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Karim Gariani Service of Endocrinology, Diabetes, Nutrition and Patient Therapeutic Education, Geneva University Hospitals, Geneva, Switzerland
Diabetes Center, Faculty of Medicine, University of Geneva, Geneva, Switzerland

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), muscle weakness in an age-dependent manner, and inflammation ( 17 , 18 ). Conversely, GDF15 levels have also been reported to be elevated in patients subjected to approaches beneficial to health such as exercise and metformin treatment ( 8 , 19 ). This

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Mônica R Gadelha Endocrine Unit, Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil

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Feng Gu Department of Endocrinology, Key Laboratory of Endocrinology, Ministry of Health, Peking Union Medical College Hospital, Beijing, China

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Marcello D Bronstein Neuroendocrine Unit, Division of Endocrinology and Metabolism, University of São Paulo Medical School, São Paulo, Brazil

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Thierry C Brue Aix-Marseille Université, Institut National de la Santé et de la Recherche Médicale, Marseille Medical Genetics, and Assistance Publique Hôpitaux de Marseille, Department of Endocrinology, Hôpital de la Conception, Centre de Référence des Maladies Rares de l’Hypophyse, Marseille, France

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Maria Fleseriu Northwest Pituitary Center, Oregon Health & Science University, Portland, Oregon, USA

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Ilan Shimon Institute of Endocrinology and Metabolism, Rabin Medical Center, and Sackler School of Medicine, Tel-Aviv University, Petah-Tiqva, Israel

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Aart J van der Lely Erasmus University Medical Center, Rotterdam, The Netherlands

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Shoba Ravichandran Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, USA

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Albert Kandra Recordati AG, Basel, Switzerland

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Alberto M Pedroncelli Recordati AG, Basel, Switzerland

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Annamaria A L Colao Dipartimento di Medicina Clinica e Chirurgia, Sezione di Endocrinologia, Università Federico II di Napoli, Naples, Italy

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groups were defined: ‘Metformin alone’ included patients who took at least one dose of metformin alone with no other oral antidiabetic (OAD) or insulin throughout the core phase ‘Metformin ± OAD’ included patients who received either metformin

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