THE COMPREHENSIVE COMPARISON OF THE EFFICACY OF FIRST-LINE DRUGS IN THE TREATMENT OF TYPE II DIABETES: METFORMIN, GLP-1 AGONISTS, AND SGLT2 INHIBITORS

Keywords: Type II Diabetes, Metformin, GLP-1 Receptor Agonist, MALA, SGLT2 Inhibitors

Abstract

Introduction: Type II diabetes is a chronic metabolic disease characterized by hyperglycemia. The goal of diabetes treatment is to achieve normal blood glucose levels and prevent complications arising from diabetes. Currently, there are many groups of antidiabetic drugs available, differing in their main indications for use, mechanism of action, and side effects, which allow the selection of the most effective and best tolerated treatment method for a specific patient.

Objective: The objective of this review was to compare the efficacy of drugs used as first-line treatments for type II diabetes, namely metformin, glucagon-like peptide-1 (GLP-1) receptor agonists, and sodium-glucose cotransporter 2 (SGLT2) inhibitors, also known as flozins, taking into account their limitations and adverse effects.

Method: In order to compare the effectiveness of metformin, GLP-1 agonists, and SGLT2 inhibitors in the treatment of type II diabetes, a systematic review was conducted between 2020 and 2025, covering the PubMed  database. Key words such as type II diabetes, metformin, GLP-1 receptor agonist, MALA, SGLT2 inhibitors were used.

Conclusions: The comparison shows that metformin, GLP-1 agonists, and SGLT2 inhibitors are effective drugs used in the treatment of type II diabetes, and the choice of the appropriate drug depends on the patient's condition, comorbidities, and the desired effects. SGLT2 inhibitors are the best choice for patients with heart failure and renal failure, while GLP-1 agonists are the most suitable for patients with high cardiovascular risk, as they reduce the risk of heart attack or stroke. Metformin, by increasing the sensitivity of peripheral tissues to insulin, is used in the treatment of both diabetes and insulin resistance. In addition, it is the cheapest of the compared groups of drugs, which may be an important aspect in the selection of therapy for individual patients coming from poor environments. All three groups lower blood glucose without the risk of hypoglycemia. Side effects mainly include gastrointestinal disorders (metformin, GLP-1) and urinary tract infections (SGLT2). Summing up the above conclusions, it can be stated that the choice of drug in diabetes therapy should mainly depend on the patient's comorbidities.

References

LIPKA, Marta, KOŃCZALSKA, Karolina and KĘDZIORA-KORNATOWSKA, Kornelia, (2020) Diabetes - diagnosis, treatment, complications and rehabilitation, Journal of Education, Health and Sport, Vol. 10, no. 8, pp. 322-331. https://doi.org/10.12775/JEHS.2020.10.08.038

Sevgican Demir, Peter P Nawroth, Stephan Herzig, Bilgen Ekim Üstünel, (2021) Emerging Targets in Type 2 Diabetes and Diabetic Complications, Advanced Science, 8(18):e2100275. https://doi.org/10.1002/advs.202100275

M A Darenskaya, L I Kolesnikova, S I Kolesnikov, (2021) Oxidative Stress: Pathogenetic Role in Diabetes Mellitus and Its Complications and Therapeutic Approaches to Correction, Bulletin of experimental biology and medicine, 171(2):179-189. https://doi.org/10.1007/s10517-021-05191-7

American Diabetes Association Professional Practice Committee, (2024) Diagnosis and Classification of Diabetes: Standards of Care in Diabetes-2024, Diabetes Care, 1;47(Suppl 1):S20-S42, https://doi.org/10.2337/dc24-S002

Traci E LaMoia, Gerald I Shulman, (2021), Cellular and Molecular Mechanisms of Metformin Action, Endocrine reviews ,42(1):77-96. https://doi.org/10.1210/endrev/bnaa023

Marc Foretz, Bruno Guigas, Benoit Viollet, (2023) Metformin: update on mechanisms of action and repurposing potential, Nature reviews. Endocrinology,19(8):460-476. https://doi.org/10.1038/s41574-023-00833-4

Stefania Di Mauro, Agnese Filippello, Alessandra Scamporrino, Francesco Purrello, Salvatore Piro, Roberta Malaguarnera, (2022), Metformin: When Should We Fear Lactic Acidosis?, International journal of molecular sciences, 23(15):8320. https://doi.org/10.3390/ijms23158320

Ziquan Lv, Yajie Guo, (2020), Metformin and Its Benefits for Various Diseases, Front Endocrinol (Lausanne), 16:11:191. https://doi.org/10.3389/fendo.2020.00191

Kay Choong See, (2024), Metformin-associated lactic acidosis: A mini review of pathophysiology, diagnosis and management in critically ill patients, World journal of diabetes, 15(6):1178-1186. https://dx.doi.org/10.4239/wjd.v15.i6.1178

Xin Zhao, Minghe Wang, Zhitong Wen, Zhihong Lu, Lijuan Cui, Chao Fu, Huan Xue, Yunfeng Liu, Yi Zhang, (2021), GLP-1 Receptor Agonists: Beyond Their Pancreatic Effects, Front Endocrinol (Lausanne), 23:12:721135. https://doi.org/10.3389/fendo.2021.721135

Michael A Nauck, Daniel R Quast, Jakob Wefers, Juris J Meier, (2020), GLP-1 receptor agonists in the treatment of type 2 diabetes - state-of-the-art, Molecular metabolism, 46:101102. https://doi.org/10.1016/j.molmet.2020.101102

Xiaoxuan Ma, Zhenghong Liu, Iqra Ilyas, Peter J Little, Danielle Kamato, Amirhossein Sahebka, Zhengfang Chen, Sihui Luo, Xueying Zheng, Jianping Weng, Suowen Xu, (2021), GLP-1 receptor agonists (GLP-1RAs): cardiovascular actions and therapeutic potential, International journal of biological sciences, 17(8):2050-2068, https://doi.org/10.7150/ijbs.59965

Steven P Marso, Gilbert H Daniels, Kirstine Brown-Frandsen, Peter Kristensen, Johannes F E Mann, Michael A Nauck, Steven E Nissen, Stuart Pocock, Neil R Poulter, Lasse S Ravn, William M Steinberg, Mette Stockner, Bernard Zinman, Richard M Bergenstal, John B Buse; LEADER Steering Committee; LEADER Trial Investigators, (2016), Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes, The New England journal of medicine, 375(4):311-22. https://www.nejm.org/doi/full/10.1056/NEJMoa1603827

Xiaoxuan Ma, Zhenghong Liu, Iqra Ilyas, Peter J Little, Danielle Kamato, Amirhossein Sahebka, Zhengfang Chen, Sihui Luo, Xueying Zheng, Jianping Weng, Suowen Xu, (2021), GLP-1 receptor agonists (GLP-1RAs): cardiovascular actions and therapeutic potential, International journal of biological sciences, 17(8):2050-2068, https://doi.org/10.7150/ijbs.59965

Manoj K Mahapatra, Muthukumar Karuppasamy, Biswa M Sahoo (2022) Therapeutic Potential of Semaglutide, a Newer GLP-1 Receptor Agonist, in Abating Obesity, Non-Alcoholic Steatohepatitis and Neurodegenerative diseases: A Narrative Review, Pharmaceutical research, 39(6):1233-1248, https://doi.org/10.1007/s11095-022-03302-1

Dion R P Muller 1 2, Dirk J Stenvers 1 2, Arjan Malekzadeh 3, Frederik Holleman 4, Rebecca C Painter 5 6, Sarah E Siegelaar (2023), Effects of GLP-1 agonists and SGLT2 inhibitors during pregnancy and lactation on offspring outcomes: a systematic review of the evidence, Front Endocrinol (Lausanne), 14:1215356, https://doi.org/10.3389/fendo.2023.1215356

Ferrannini, G., Savarese, G., & Cosentino, F. (2022). SGLT2 Inhibitors in Type 2 Diabetes Mellitus. Heart failure clinics, 18(4), 551–559. https://doi.org/10.1016/j.hfc.2022.03.009

Rizzo, M. R., Di Meo, I., Polito, R., Auriemma, M. C., Gambardella, A., di Mauro, G., Capuano, A., & Paolisso, G. (2022). Cognitive impairment and type 2 diabetes mellitus: Focus of SGLT2 inhibitors treatment. Pharmacological research, 176, 106062. https://doi.org/10.1016/j.phrs.2022.106062

Wright E. M. (2021). SGLT2 Inhibitors: Physiology and Pharmacology. Kidney360, 2(12), 2027–2037. https://doi.org/10.34067/KID.0002772021

Dharia, A., Khan, A., Sridhar, V. S., & Cherney, D. Z. I. (2023). SGLT2 Inhibitors: The Sweet Success for Kidneys. Annual review of medicine, 74, 369–384. https://doi.org/10.1146/annurev-med-042921-102135

Vaduganathan, M., Docherty, K. F., Claggett, B. L., Jhund, P. S., de Boer, R. A., Hernandez, A. F., Inzucchi, S. E., Kosiborod, M. N., Lam, C. S. P., Martinez, F., Shah, S. J., Desai, A. S., McMurray, J. J. V., & Solomon, S. D. (2022). SGLT-2 inhibitors in patients with heart failure: a comprehensive meta-analysis of five randomised controlled trials. Lancet (London, England), 400(10354), 757–767. https://doi.org/10.1016/S0140-6736(22)01429-5

Nuffield Department of Population Health Renal Studies Group, & SGLT2 inhibitor Meta-Analysis Cardio-Renal Trialists' Consortium (2022). Impact of diabetes on the effects of sodium glucose co-transporter-2 inhibitors on kidney outcomes: collaborative meta-analysis of large placebo-controlled trials. Lancet (London, England), 400(10365), 1788–1801. https://doi.org/10.1016/S0140-6736(22)02074-8

Kittipibul, V., Cox, Z. L., Chesdachai, S., Fiuzat, M., Lindenfeld, J., & Mentz, R. J. (2024). Genitourinary Tract Infections in Patients Taking SGLT2 Inhibitors: JACC Review Topic of the Week. Journal of the American College of Cardiology, 83(16), 1568–1578. https://doi.org/10.1016/j.jacc.2024.01.040

Morace, C., Lorello, G., Bellone, F., Quartarone, C., Ruggeri, D., Giandalia, A., Mandraffino, G., Minutoli, L., Squadrito, G., Russo, G. T., & Marini, H. R. (2024). Ketoacidosis and SGLT2 Inhibitors: A Narrative Review. Metabolites, 14(5), 264. https://doi.org/10.3390/metabo14050264

Kuoni, S., Steiner, R., Saleh, L., Lehmann, R., Ochsenbein-Kölble, N., & Simões-Wüst, A. P. (2024). Safety assessment of the SGLT2 inhibitors empagliflozin, dapagliflozin and canagliflozin during pregnancy: An ex vivo human placenta perfusion and in vitro study. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 171, 116177. https://doi.org/10.1016/j.biopha.2024.116177

Muller, D. R. P., Stenvers, D. J., Malekzadeh, A., Holleman, F., Painter, R. C., & Siegelaar, S. E. (2023). Effects of GLP-1 agonists and SGLT2 inhibitors during pregnancy and lactation on offspring outcomes: a systematic review of the evidence. Frontiers in endocrinology, 14, 1215356. https://doi.org/10.3389/fendo.2023.1215356

Młynarska, E., Czarnik, W., Dzieża, N., Jędraszak, W., Majchrowicz, G., Prusinowski, F., Stabrawa, M., Rysz, J., & Franczyk, B. (2025). Type 2 Diabetes Mellitus: New Pathogenetic Mechanisms, Treatment and the Most Important Complications. International journal of molecular sciences, 26(3), 1094. https://doi.org/10.3390/ijms26031094

Drake, T., Landsteiner, A., Langsetmo, L., MacDonald, R., Anthony, M., Kalinowski, C., Ullman, K., Billington, C. J., Kaka, A., Sultan, S., & Wilt, T. J. (2024). Newer Pharmacologic Treatments in Adults With Type 2 Diabetes: A Systematic Review and Network Meta-analysis for the American College of Physicians. Annals of internal medicine, 177(5), 618–632. https://doi.org/10.7326/M23-1490

Forzano, I., Varzideh, F., Avvisato, R., Jankauskas, S. S., Mone, P., & Santulli, G. (2022). Tirzepatide: A Systematic Update. International journal of molecular sciences, 23(23), 14631. https://doi.org/10.3390/ijms232314631

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Published
2025-09-30
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How to Cite
Anna Kamieniak, & Dominika Gieroba. (2025). THE COMPREHENSIVE COMPARISON OF THE EFFICACY OF FIRST-LINE DRUGS IN THE TREATMENT OF TYPE II DIABETES: METFORMIN, GLP-1 AGONISTS, AND SGLT2 INHIBITORS. International Journal of Innovative Technologies in Social Science, 6(3(47). https://doi.org/10.31435/ijitss.3(47).2025.3884

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