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 recommendations of future therapeutics.

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. elaborated several new insights in metformin action.

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

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

**II**

**Section 3**

on Cancer

**Section 4**

*and Andra-Iulia Suceveanu*

Metformin and Cancer **111**

**Chapter 7 113**

**Chapter 8 127**

**Chapter 9 149**

**Chapter 10 163**

**Chapter 11 181**

Metformin and Ageing **209**

**Chapter 12 211**

*by Adriana Florinela Cӑtoi, Andra Diana Andreicuț, Dan Cristian Vodnar, Katalin Szabo, Andreea Corina, Andreea Arsene, Simona Diana Stefan,* 

*Adrian-Paul Suceveanu, Irinel Parepa, Felix Voinea, Doina Catrinoiu* 

Preventive and (Neo)Adjuvant Therapeutic Effects of Metformin

Metformin Activity against Breast Cancer: Mechanistic Differences

Metformin in Cervical Cancer: Metabolic Reprogramming

*by Malgorzata Tyszka-Czochara and Marcin Majka*

by Molecular Subtype and Metabolic Conditions *by Reema S. Wahdan-Alaswad and Ann D. Thor*

Metformin Modulates the Mechanisms of Ageing

*Roxana Adriana Stoica and Manfredi Rizzo*

Antitumoral Effects of Metformin in Ovarian Cancer *by Maritza P. Garrido, Margarita Vega and Carmen Romero*

Metformin and Its Implication in Cancer Therapy *by Laura Mazilu, Dana Stanculeanu, Andreea Gheorghe,* 

*by Yile Jiao, Xiaochen Wang and Zhijun Luo*

### **Anca Mihaela Pantea Stoian**

Diabetes, Nutrition and Metabolic Diseases Department, Carol Davila University of Medicine, Bucharest, Romania

**Manfredi Rizzo** Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of South Carolina, Columbia, SC, USA

> Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, University of Palermo, Italy

**1**

Section 1

Metformin and Diabetes

Mellitus

### Section 1
