Meet the editors

Dr Pantea Stoian is a diabetes, nutrition and metabolic diseases specialist, a senior specialist in health food hygiene, a resident in nephrology, and is competent in medical aesthetics and general ultrasonography. She has held an Associate Professor in the Diabetes, Nutrition, and Metabolic Diseases Department since 2019 at "Carol Davila" University of Medicine, Bucharest, Romania. Her field of activity is closely related to the micro- and

macro-vascular complications in diabetes as well as their new therapies. Its main directions of activity are nutritional intervention in chronic pathology, as well as cardio-renal-metabolic risk assessment, and diabetes in cancer. In diabetes, she is currently engaged in new therapy and technology tools that screen and prevent diabetes and educate patients. She is a member of the European Association for the Study of Diabetes, Cardiometabolic Academy, Romanian Society of Diabetes, Nutrition and Metabolic Diseases, Romanian Diabetes Federation and Association for Renal Metabolic and Nutrition Studies. She has authored or co-authored 110 papers in national and international peer-reviewed journals.

Prof. Manfredi Rizzo, MD, PhD. Prof. Rizzo studied medicine and received training in Internal Medicine in Italy. He spent several years in the United States, working at the University of California. There he was able to gain clinical and research experience on patients with different metabolic disorders, including dyslipidemia, diabetes, obesity, and metabolic syndrome. He is also the Head of the Cardiometabolic Research Laboratory

of the Department of Internal Medicine at the University of Palermo. Prof. Rizzo maintains a faculty position in the USA, where he is Adjunct Associate Professor of Internal Medicine at the School of Medicine, University of South Carolina, with a research position in the Division of Endocrinology, Diabetes, and Metabolism. Currently, Prof. Rizzo is on sabbatical leave since he joined Novo Nordisk in 2019 as a Director of the Clinical, Medical & Regulatory Department, Novo Nordisk Europe East and South. Prof. Rizzo sits on the editorial board of 10 international journals. The research work of Prof. Rizzo combines translational and primary research, with 250+ scientific publications in international journals. Finally, Prof. Rizzo has been the Coordinator, Vice-Chairman or Co-Chairman of international expert panel documents in the field of dyslipidemia, diabetes, and metabolic syndrome. He is currently a National Board Member of the Italian Society of Nutraceuticals (SINUT) and Executive Board Member of the Mediterranean Group for the Study of Diabetes (MGSD).

Contents

**Section 1**

Application

**Section 2**

*by Elham Pourmatroud*

in Diabetes Patients

*and Adrian-Paul Suceveanu*

in Patients with Type 2 Diabetes

and Contraindications

*and Anca Pantea-Stoian*

**Preface III**

Metformin and Diabetes Mellitus **1**

**Chapter 1 3**

**Chapter 2 21**

**Chapter 3 45**

**Chapter 4 61**

**Chapter 5 75**

Metformin and Reproductive System **97**

**Chapter 6 99**

Metformin Indications, Dosage, Adverse Reactions,

*by Yun Yan, Karen L. Kover and Wayne V. Moore*

*by Roxana Adriana Stoica, Diana Simona Ștefan, Manfredi Rizzo, Andra Iulia Suceveanu, Adrian Paul Suceveanu, Cristian Serafinceanu* 

New Insight into Metformin Mechanism of Action and Clinical

*by Andra Iulia-Suceveanu, Sergiu Ioan Micu, Claudia Voinea, Madalina Elena Manea, Doina Catrinoiu, Laura Mazilu, Anca Pantea Stoian, Irinel Parepa, Roxana Adriana Stoica* 

*by Jasna Kusturica, Aida Kulo, Maida Rakanović-Todić,* 

Metformin in Health Issues and Reproductive System

*Lejla Burnazović-Ristić and Sanita Maleškić*

Metformin and Its Benefits in Improving Gut Microbiota Disturbances

Potential Protective Effects of Metformin on Ocular Complications

*Galega officinalis* L. and Immunological Status in Diabetes Mellitus *by Mariia Nagalievska, Halyna Hachkova and Nataliia Sybirna*

## Contents



Preface

Metformin has been in clinical practice since 1957, having a sinuous route to date. There have been many books, articles, and studies related to metformin, thus discovering many therapeutic values. The book brings to light both the standard therapeutic recommendations, namely, the first-intention therapy in patients with type 2 diabetes and current trends in use. Metformin can now be regarded as a panacea, the valences of its therapeutics being increasingly appreciated, both in the background treatmen t of diabetes, prediabetes, but also in reproductive pathology, cancer, cardiovascular disease, and antiaging. In this respect, the mechanisms of action and the pharmacodynamics of metformin seem to be incompletely known; several current studies have revealed new action valences. The function of these pharmacogenetic mechanisms, as well as the mode of action of metformin, needs to be known because they also predict the recom-

Its significant role in the treatment of type 2 diabetes is recognized by all international guidelines in the field, placing it in the first line of treatment along with lifestyle optimization. New evidence also appears in the use of metformin in patients with type 1 diabetes, especially in those who develop insulin resistance. Some chapters explain adverse effects, indications, and contraindications of metformin and also its implication in gut microbiota. Immunological status in diabetes and the role of metformin was described very extensively by Prof. Mariia Nagalievska et al. in their chapter, and Prof. Yun Yan et al.

The international specialty literature brings new evidence in initiating metformin therapy in prediabetes, but also the prevention of cancer or reproductive system diseases, and cardiovascular or gastrointestinal disorders. In this way, several chapters have been dedicated to the reproductive system and to the role of metformin in cancer

An important role of metformin is immune system modulation as well as antiaging therapy. A chapter was dedicated to the mechanism of ageing and the part of metformin

Division of Endocrinology, Diabetes and Metabolism, Department of Medicine,

**Anca Mihaela Pantea Stoian**

University of South Carolina,

Bucharest, Romania **Manfredi Rizzo**

Columbia, SC, USA

University of Palermo,

Italy

Carol Davila University of Medicine,

Internal Medicine and Medical Specialties,

Diabetes, Nutrition and Metabolic Diseases Department,

Department of Health Promotion, Mother and Child Care,

therapy, especially in cervical cancer, ovarian cancer, and breast cancer.

I hope this book is a key for every reader to open new insights to metformin.

mendations of future therapeutics.

in preventing ageing.

elaborated several new insights in metformin action.
