Clinical Efficacy and Safety of Metformin in Prediabetics
DOI:
https://doi.org/10.52206/jsmc.2025.15.2.1002Abstract
Background: Prediabetes is defined as a state of abnormal glucose homeostasis, HbA1c 5.7% to 6.4% and fasting blood glucose 100 mg/dl to 125mg/dl. Mainstay of treatment in prediabetes is lifestyle changes. However if not controlled pharmacotherapy is added. Metformin HCL is a biguanide drug.
Objectives: To evaluate clinical efficacy of metformin HCl with lifestyle modifications and to assess the adverse effects, safety profile and cost effectiveness of metformin in pre-diabetics.
Materials and Methods: This randomized controlled clinical trial (RCT) was conducted at diabetic clinics of National Medical Centre and Bay View Hospital Karachi. Individual study duration was 3 months. This randomized controlled clinical trial (RCT) is registered at clinicaltrials.gov, bearing NCT number. Males and females, 17-40 years of age, were included. Metformin HCl was given 500 mg orally BD for 12 weeks alongwith lifestyle modification. Anthropometric parameters were evaluated at baseline week 6 and week 12. Metabolic parameters and safety profile parameters were evaluated at baseline and week 12. Adverse effects were assessed at 6 and week 12 whereas cost effectiveness at the end of study.
Results: Majority of participants were in age group 32 to 40 years. Weight, HBA1c, FBS were highly significantly reduced, HDL was significantly increased. Metformin was found to be safe. No adverse effects were reported.
Conclusion: Metformin is clinically effectively reduced weight, improved FBG and HbA1c in prediabetics. Metformin was safe for the dose and duration used and devoid of adverse effects in prediabetics. Metformin is very cost effective.
Keywords: FBG, HbA1c, HCL, Lifestyle changes, Metformin HCL, Pre-diabetes, Weight.
References
Tcheugui E, Selvin E. Prediabetes and What It Means: The Epidemiological Evidence. Annu Rev Public Health. 2021; 42:59-77. https://doi.org/10.1146/annurev-publhealth-090419-102644
Classification and diagnosis of diabetes: standards of care in diabetes-2023. Diabetes care, 46, S19- S40. https://doi.org/10.2337/dc23-S002
Azeem S, Khan U , Liaquat, A. The increasing rate of diabetes in Pakistan: A silent killer. Annals of Medicine and Surgery. 2022; 79. https://doi.org/10.1016/j.amsu.2022.103901
Francois ME, Oetsch KM. Prediabetes: Challenges, Novel Solutions, and Future Directions. European Medical Journal. 2022. https://doi.org/10.33590/emj/21-00148
Zuniga RE, DeBoer MD. Prediabetes in Adolescents: Prevalence, Management and Diabetes Prevention Strategies. Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy. 2021; 14: 4609-461. https://doi.org/10.2147/DMSO.S284401
Jack SD, Umekwe N, Brewer AA, Owei I, Mupparaju V, Rosenthal R, et al. Outcome of lifestyle intervention in relation to duration of pre-diabetes: the Pathobiology and Reversibility of Prediabetes in a Biracial Cohort (PROP-ABC) study. BMJ Open Diabetes Res Care. 2022; 10(2):1-9. https://doi.org/10.1136/bmjdrc-2021-002748
Barrea L, Vetrani C, Verde L, Toral F E, Ceriani F, Cernea S, et al. Comprehensive Approach to Medical Nutrition Therapy in Patients with Type 2 Diabetes Mellitus: From Diet to Bioactive Compounds. Antioxidants. 2023;12(4):904. https://doi.org/10.3390/antiox12040904
Hostalek U, Campbell I. Metformin for diabetes prevention: update of the evidence base. Current Medical Research and Opinion, 2021;37(10):1705- 1717. https://doi.org/10.1080/03007995.2021.1955667
Espinoza SE, Musi N, Wang CP, Michalek J, Orsak B, Romo T. Rationale and Study Design of a Randomized Clinical Trial of Metformin to Prevent Frailty in Older Adults with Prediabetes. J Gerontol A Biol Sci Med Sci. 2020 ;75(1):102-109. https://doi.org/10.1093/gerona/glz078
Sinnappah, KA, Kuan IH, Thynne TR, Doogue MP, Wright DF. The pharmacokinetics of metformin in patients receiving intermittent haemodialysis. British Journal of Clinical Pharmacology. 2020; 86(7): 1430-1443. https://doi.org/10.1111/bcp.14244
Triggle CR, Mohammed I, Bshesh K, Marei I, Ding H. Metformin: is it a drug for all reasons and diseases? Metabolism. 2022; 133: 155223. https://doi.org/10.1016/j.metabol.2022.155223
?uczak K, Musialik M, Szuli?ska K, Swora- Cwynar EM, Kargulewicz A, Grzymis?awska, et al. The effect of orlistat versus metformin on body composition and insulin resistance in obese premenopausal women: 3-month randomized prospective open-label study. Archives of Medical Science. 2017; 13(4):725-731. https://doi.org/10.5114/aoms.2016.62014
Qudah SAA, Hamaideh KDA, Dmour IM, Samar Sameer Al Sbaihi SS. Overweight management: A cross-sectional study with special insight on metformin use in obesity control. Journal of Applied Pharmaceutical Science. 2022; 12(8): 179-186. https://doi.org/10.7324/JAPS.2022.120818
Farhadian M, Barati S, Mahmoodi M, Mosleh AB, Yavangui M. Comparison of green tea and metformin effects on anthropometric indicators in women with polycystic ovarian syndrome: a clinical trial study. Journal of Reports in Pharmaceutical Sciences. 2020; 9(1):97. https://doi.org/10.4103/jrptps.JRPTPS_14_19
Izadi I, Samani RR, Tehrani AM, Dehghani M, Jafari A. Glucoherb versus metformin on glycemic markers and glycosylated hemoglobin in prediabetes patients; a clinical trial study. Journal of Nephropharmacology. 2020; 10(1):e08-e08. https://doi.org/10.34172/npj.2021.08
Glechner A, Keuchel L, Affengruber L, Titscher V, Sommer I, Matyas N. Effects of lifestyle changes on adults with prediabetes: A systematic review and meta-analysis. Primary Care Diabetes. 2018;12: 399-408. PMid:30076075 https://doi.org/10.1016/j.pcd.2018.07.003
Ko KP, Ma SH, Yang JJ, Hwang Y, Ahn C, Cho YM. Metformin intervention in obese non-diabetic patients with breast cancer: phase II randomized, double-blind, placebo-controlled trial. Clinical trial. 2015; 153 :361-370. https://doi.org/10.1007/s10549-015-3519-8
Sauriasari R, Buri FSN, Azizahwati A. Effect of metformin and metformin-sulfonylurea on lipid profile of type 2 diabetes mellitus patients: A cross- sectional study. Istanbul J Pharm. 2022; 52 (2): 114- 120. https://doi.org/10.26650/IstanbulJPharm.2022.957738
Basit A, Fawwad A, Basit KA, Waris N, Tahir B, Siddiqui IA. Glycated hemoglobin (HbA1c) as diagnostic criteria for diabetes: the optimal cut-off points values for the Pakistani population; a study from second National Diabetes Survey of Pakistan (NDSP) 2016-2017. BMJ Open Diabetes. 2020. Research and Care, 8(1), e001058. https://doi.org/10.1136/bmjdrc-2019-001058
Gillani SW, Ghayedi N, Roosta P,Seddigh P,Nasiri O. Effect of Metformin on Lipid Profiles of Type 2 Diabetes Mellitus: A Meta-analysis of Randomized Controlled Trials. J Pharm Bioallied Sci. 2021; 13(1): 76-82. https://doi.org/10.4103/jpbs.JPBS_370_20
Luo F, Das A, Chen J, Wu P, Li X, Fang Z. Metformin in patients with and without diabetes: a paradigm shift in cardiovascular disease management. Cardiovascular diabetology. 2019; 18(1): 1-9. https://doi.org/10.1186/s12933-019-0860-y
Hu D, Guo Y, Wu R, Shao T, Long J, Yu B. New Insight Into Metformin-Induced Cholesterol- Lowering Effect Crosstalk Between Glucose and Cholesterol Homeostasis via ChREBP (Carbohydrate-Responsive Element-Binding Protein)-Mediated PCSK9 (Proprotein Convertase Subtilisin/Kexin Type 9) Regulation. Arteriosclerosis, Thrombosis, and Vascular Biology. 2021;41:e208-e223. https://doi.org/10.1161/ATVBAHA.120.315708
Koç Z. Evaluation of Low Dose Metformin Response and Dyslipidemia Levelsin Patients with Pre- diabetes South. Clin. Ist. Euras. 2022;33(4):399-405. https://doi.org/10.14744/scie.2022.72677
Alvarez CA, Halm EA, Pugh MJV. Lactic acidosis incidence with metformin in patients with type 2 diabetes and chronic kidney disease: a retrospective nested case-control study. Endocrinol Diabetes Metab. 2021; 4:e00170. https://doi.org/10.1002/edm2.170
Gabriel R, Abdelkader NB, Januszewska AG, Makrilakis K, Huelgas RG, Zdravko K, et al. Reduction in the Risk of Peripheral Neuropathy and Lower Decrease in Kidney Function with Metformin, Linagliptin or Their Fixed-Dose Combination Compared to Placebo in Prediabetes: A Randomized Controlled Trial. J. Clin. Med. 2023, 12(5), 2035. https://doi.org/10.3390/jcm12052035
Additional Files
Published
How to Cite
Issue
Section
License
Copyright (c) 2024 The authors retain the copyrights. Authors are permitted and encouraged to post their work online (e.g. in institutional repositories or on their website), as it can lead to productive exchanges, as well as greater citation of published work.
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
Readers may “Share-copy and redistribute the material in any medium or format” and “Adapt-remix, transform, and build upon the material”. The readers must give appropriate credit to the source of the material and indicate if changes were made to the material. Readers may not use the material for commercial purpose. The readers may not apply legal terms or technological measures that legally restrict others from doing anything the license permits.
