Review Article BIOEQUIVALENCE OF METFORMIN AS AN ORAL ANTIDIABETIC: A SYSTEMATIC REVIEW FITRIANTI DARUSMAN 1,2* , TAOFIK RUSDIANA 2 , IYAN SOPYAN 2 , NIKEN FITRIA YULIAR 1 , RATIH ARYANI 1 1 Department of Pharmacy, Faculty of Mathematics and Natural Sciences, Universitas Islam Bandung, Bandung, West Java, Indonesia. 2 Department of Pharmaceutical and Technology of Pharmacy, Faculty of Pharmacy, Universitas Padjadjaran, Sumedang, West Java, Indonesia * Corresponding author: Fitrianti Darusman; * Email: efit.bien@gmail.com Received: 02 Aug 2023, Revised and Accepted: 09 Oct 2023 ABSTRACT Metformin is the first line in type 2 Diabetes Mellitus (DM). Metformin is available as an innovator drug and copy drug. The high price of innovator drugs makes it difficult for patients to obtain the required drugs. Therefore, many pharmaceutical industries have developed a copy of the innovator drug. To obtain .a distribution license, the pharmaceutical industry must conduct a bioequivalence test on metformin copy tablets to ensure that the copy drug has the same efficacy, safety, and quality as the innovator drug. However, several surveys show that most patients believe that the effectiveness of copy drugs is not equivalent to the innovator drug. This study aims to determine the bioavailability profile and bioequivalence profile of Metformin copy tablets to Glucophage ® (Merck) innovator tablets so that it can provide an overview of the effectiveness of copy drugs with innovator drugs and the public no longer hesitate to use copy drugs. Metformin copy tablets are declared bioequivalent to the innovator drug if they provide a Confidence Interval (CI) value of 90% in the 80-125% range. All 500 mg, 850 mg, and 1000 mg doses of metformin copy tablets, both fasting and eating conditions, gave bioequivalent results to the innovator Glucophage ® based on 90% CI. Keywords: Bioequivalence, Bioavailability, Pharmacokinetics, Glucophage ® , Metformin © 2023 The Authors. Published by Innovare Academic Sciences Pvt Ltd. This is an open access article under the CC BY license (https://creativecommons.org/licenses/by/4.0/) DOI: https://dx.doi.org/10.22159/ijap.2023v15i6.49142. Journal homepage: https://innovareacademics.in/journals/index.php/ijap INTRODUCTION Diabetes mellitus (DM) is a metabolic disorder characterized by elevated blood glucose levels due to impaired insulin secretion and/or impaired insulin sensitivity. According to the International Diabetes Federation (IDF), approximately 10.5% of the world's population lives with diabetes at the age of 20-79 y old [1]. The first line of pharmacologic therapy used in type 2 DM is metformin. Metformin is mainly used because it has a low risk of side effects of hypoglycemia and has no impact on body weight. To achieve maximum blood glucose-lowering effect, metformin is commonly combined with other blood glucose-lowering agents, such as thiazolidinediones [2]. Metformin is a medicine used to treat type 2 DM. Metformin is a derivative of Galegin, a compound from the Galega officinalis plant that was used for herbal medicine in Europe. In the 1920s, Galegine was tested as a glucose-lowering agent in humans, but the results were found as toxic to humans. At the same time, synthetic derivatives of Galegine were synthesized, namely Metformin and Phenformin. However, phenformin is no longer widely used due to side effects such as lactic acidosis [3]. Metformin is widely used as an antidiabetic, followed by sulfonylureas and insulin [4]. Metformin is available in the form of an innovator drug and copy drug. The high price of the innovator drug makes it difficult for patients to obtain the drug they need, so the pharmaceutical industry develops a copy of the innovator drug. To be approved for distribution, a copy drug must be bioequivalent to the comparator drug as proven through a bioequivalence study [5]. A bioequivalence study is a test that compares the bioavailability profile between a test drug and a comparator drug [1]. Even though they have passed bioequivalence tests, some surveys show that most patients believe a copy drug’s effectiveness is not equivalent to the innovator drug [6]. The main objective of this review was to determine the bioequivalence profile of Metformin copy tablets to Glucophage ® (Merck) as innovator tablets so it can provide an overview of the effectiveness of copy drugs with innovator drugs and the public no longer hesitate to use copy drug. Methods Research article search on reputable databases, which are PubMed, ScienceDirect (Elsevier), John Wiley and Sons, and Springer Verlag collected in December 2022-January 2023. The inclusion criteria for articles are research articles on the bioequivalence study of metformin copy tablets, research articles with metformin copy tablets with doses of 500 mg, 850 mg, and 1000 mg, research articles published in the last 10 y (2013-2023), and articles written in Indonesian or English. Articles excluded have criteria that do not discuss the bioequivalence study of metformin. The extracted data are the main author’s name, year of publication, study design, number of participants, doses, test and innovator drug data, Area Under Curve (AUC0-∞ and AUC0-t), time taken to reach the highest concentration (Tmaks), highest concentration (Cmaks), T1/2, and 90% Confidence Interval (CI). Fig. 1 shows the PRISMA flow diagram of the article selection process. Fig. 1: PRISMA flow diagram of article research International Journal of Applied Pharmaceutics ISSN- 0975-7058 Vol 15, Issue 6, 2023