Metformin is widely used drugs in the treatment of type 2 diabetes mellitus. However, the mechanisms of action are complex and are still not fully understood yet. Metformin has a dose-dependent blood sugar-lowering effect. The most common adverse reactions of metformin are gastrointestinal symptoms, and women tend to be more experienced than men. A positive correlation between the administration of duration and the daily dose of metformin and the risk of vitamin B12 deficiency is confirmed. Novel glucose-lowering mechanism through the activation of AMP-activated protein kinase and alteration of gut microbiota composition is identified. In addition, metformin has immunomodulatory properties in various mechanisms, including anti-inflammatory actions, and so forth. Metformin improves insulin sensitivity, which may reduce the risk of tumor growth in certain cancers. The antiviral effects of metformin may occur through several mechanisms, including blocking angiotensin converting enzyme 2 receptor, and so forth. These potential mechanisms of metformin are promising in various clinical settings, such as inflammatory diseases, autoimmune diseases, cancer, and coronavirus disease 2019.

Citations

• USING BIOPELLETS WITH METFORMIN IN THE EXPERIMENTAL METABOLIC SYNDROME
  N. I. Voloshchuk, V. G. Zolotareva, A. V. Hara, O. S. Pashynska, I. V. Taran, A. V. Melnyk, V. O. Denysiuk
  World of Medicine and Biology.2024; 20(89): 220.     CrossRef
• Metformin in Antiviral Therapy: Evidence and Perspectives
  Iryna Halabitska, Pavlo Petakh, Oleh Lushchak, Iryna Kamyshna, Valentyn Oksenych, Oleksandr Kamyshnyi
  Viruses.2024; 16(12): 1938.     CrossRef

Metformin is the most widely used antihyperglycemic drug in patients with type 2 diabetes (T2D). Over the past 2 decades, several studies have highlighted a substantial increase in the risk of vitamin B12 deficiency in patients with T2D on metformin therapy. This can lead to several complications and induce or exacerbate peripheral neuropathy. Despite these data, there are no definite guidelines for screening, diagnosing, and treating vitamin B12 deficiency in patients with T2D on metformin therapy. Therefore, in this narrative review, we aimed to suggest a practical diagnostic and therapeutic strategy to address vitamin B12 deficiency in patients with T2D receiving metformin treatment. Clinical evidence supporting an increased risk of vitamin B12 deficiency in patients with T2D on metformin therapy and its risk factors and potential complications are also discussed.

Citations

• Correlation between vitamin B12 deficiency and hemoglobin A1c in patients with diabetes mellitus
  Yahya Madkhali, Sami G. Almalki
  Journal of King Saud University – Science.2025; 37: 3542024.     CrossRef
• Rethinking about Metformin: Promising Potentials
  Kyunam Kim
  Korean Journal of Family Medicine.2024; 45(5): 258.     CrossRef
• Prevalence of Vitamin B12 Deficiency in Patients With Type 2 Diabetes Mellitus on Metformin Therapy: A Cross-Sectional Study
  Shoaib Asghar, Haider Tanvir, Asad Riaz, Muhammad Hamza Ejaz, Mamuna Akram, Al Muktadir Chowdhury Evan, Salman Shahid
  Cureus.2024;[Epub]     CrossRef

Background
In addition to its antidiabetic effects, metformin has pleiotropic effects, such as the inhibition of carcinogenesis. This study aimed to investigate the association between metformin use and pancreatic cancer risk in the Korean National Health Insurance Service (NHIS)-National Health Screening Cohort (HEALS).
Methods
Of the individuals in the Korean NHIS-HEALS, 29,271 men and 19,091 women were included in the final analysis after propensity score matching based on age, body mass index, and smoking status. The study population was categorized into three groups: metformin non-users with diabetes mellitus (DM), metformin users with DM, and non-diabetic users. A Cox proportional hazards regression model was used to examine the association between metformin use and pancreatic cancer.
Results
The median follow-up period was 12.9 years. The estimated pancreatic cancer incidence was highest in metformin users with DM, regardless of sex (P<0.001), and lowest in non-diabetic men and female metformin non-users (P=0.053). The hazard ratios (95% confidence interval) for pancreatic cancer incidence in metformin users and non-diabetic individuals were 1.116 (0.648–1.923) and 0.447 (0.259–0.771) in men and 2.769 (1.003–7.642) and 1.451 (0.529–3.984) in women, respectively, after full adjustment.
Conclusion
Women with diabetes using metformin are at a higher risk of pancreatic cancer than women with diabetes not using metformin. Meanwhile, men with DM using metformin have a similar risk of pancreatic cancer as men with DM not using metformin.

Citations

• Metformin: A Dual-Role Player in Cancer Treatment and Prevention: A Comprehensive Systematic Review and Meta-Analysis
  Imran Rangraze, Adil Farooq Wali, Mohamed El-Tanani, Mohamed Anas Patni, Syed Arman Rabbani, Rasha Babiker, Shakta Mani Satyam, Yahia El-Tanani, Manfredi Rizzo
  Medicina.2025; 61(6): 1021.     CrossRef
• Metformin adverse event profile: a pharmacovigilance study based on the FDA Adverse Event Reporting System (FAERS) from 2004 to 2022
  Yikuan Du, Jinfeng Zhu, Zhuoming Guo, Zhenjie Wang, Yuni Wang, Mianda Hu, Lingzhi Zhang, Yurong Yang, Jinjin Wang, Yixing Huang, Peiying Huang, Mianhai Chen, Bo Chen, Chun Yang
  Expert Review of Clinical Pharmacology.2024; 17(2): 189.     CrossRef
• Metformin: A Dual-Role Player in Cancer Treatment and Prevention
  Mariam Ahmed Galal, Mohammed Al-Rimawi, Abdurrahman Hajeer, Huda Dahman, Samhar Alouch, Ahmad Aljada
  International Journal of Molecular Sciences.2024; 25(7): 4083.     CrossRef
• Anti-Diabetic Therapies and Cancer: From Bench to Bedside
  Dimitris Kounatidis, Natalia G. Vallianou, Irene Karampela, Eleni Rebelos, Marina Kouveletsou, Vasileios Dalopoulos, Petros Koufopoulos, Evanthia Diakoumopoulou, Nikolaos Tentolouris, Maria Dalamaga
  Biomolecules.2024; 14(11): 1479.     CrossRef
• Exploring the Basic Molecular Pathways: Metformin as a Potential Treatment Option for Pancreatic Cancer
  Sepehr Ramezani, Dariush Moslemi, Faezeh Firuzpour, Hamidreza Didar, Seyedamirmohammad Mazloumi, Narjes rezaeiroushan
  Iranian Journal of Blood and Cancer.2024; 16(4): 56.     CrossRef
• Diabetes Mellitus in Pancreatic Cancer: A Distinct Approach to Older Subjects with New-Onset Diabetes Mellitus
  Jan Bures, Darina Kohoutova, Jan Skrha, Bohus Bunganic, Ondrej Ngo, Stepan Suchanek, Pavel Skrha, Miroslav Zavoral
  Cancers.2023; 15(14): 3669.     CrossRef

Background
We assessed the frequency and severity of hypoglycemia in type 2 diabetes mellitus patients treated with sulfonylurea monotherapy or sulfonylurea+metformin.
Methods
We conducted a retrospective, observational, cross-sectional study in 2011 and 2012 including patients with type 2 diabetes mellitus aged ≥30 years who were treated with ≥6 months of sulfonylurea monotherapy or sulfonylurea+metformin at 20 university-affiliated hospitals in Korea. At enrollment, glycated hemoglobin (HbA1c) was assessed; participants completed self-reported questionnaires describing hypoglycemia incidents over the past 6 months. A review of medical records up to 12 months before enrollment provided data on demographics, disease history, comorbidities, laboratory results, and drug usage.
Results
Of 726 enrolled patients, 719 were included (55.6% male); 31.7% and 68.3% were on sulfonylurea monotherapy and sulfonylurea+metformin, respectively. Mean±standard deviation age was 65.9±10.0 years; mean HbA1c level was 7.0%±1.0%; 77.8% of patients had hypertension (89.4% used antihypertensive medication); 60.5% had lipid disorders (72.5% used lipid-lowering medication); and 52.0% had one or more micro- or macrovascular diseases. Among patients with A1c measurement (n=717), 56.4% achieved therapeutic goals (HbA1c <7.0%); 42.4% (305/719) experienced hypoglycemia within 6 months of enrollment; and 38.8%, 12.9%, 12.7%, and 3.9% of patients experienced mild, moderate, severe, and very severe hypoglycemia symptoms, respectively. Several reported hypoglycemia frequency as 1–2 times over the last 6 months. The mean number of very severe hypoglycemia episodes was 3.5±5.5.
Conclusion
Among type 2 diabetes mellitus patients treated with sulfonylurea-based regimens, glycemic levels were relatively well controlled but hypoglycemia remained a prevalent side effect.

Citations

• Increasing Individual Target Glucose Levels to Prevent Hypoglycemia in Patients with Diabetes
  Juyoung Shin, Hyunah Kim, Hun-Sung Kim, Churlmin Kim, Whan-Seok Choi
  Korean Journal of Family Medicine.2021; 42(4): 269.     CrossRef
• Professional Continuous Glucose Monitoring Reveals Nocturnal Hypoglycemia in Patients with Type 2 Diabetes Mellitus and Cardiovascular Disease Treated with Oral Antidiabetics
  Maja Baretić, Valerija Bralić Lang
  Korean Journal of Family Medicine.2021; 42(2): 185.     CrossRef
• Exercise Strategies to Prevent Hypoglycemia in Patients with Diabetes
  Ah Reum Jung, Hyunah Kim, Hun-Sung Kim, Churlmin Kim, Whan-Seok Choi
  Korean Journal of Family Medicine.2021; 42(2): 91.     CrossRef