Comparative Study of Efficacy and Adverse Effects of Metformin Plus Empagliflozin Versus Metformin Plus Sitagliptin in Diabetes Mellitus Type II Patients
DOI:
https://doi.org/10.70749/ijbr.v3i7.1254Keywords:
Type 2 Diabetes Mellitus, Empagliflozin, Metformin, SitagliptinAbstract
Introduction: This study aims to compare the efficacy and adverse effects of metformin combined with empagliflozin versus metformin combined with sitagliptin in Type II DM patients in Pakistan. Given the rising prevalence of diabetes in Pakistan, evaluating these widely used combination therapies in a local population is essential for optimizing treatment strategies. This research will provide valuable insights into glycemic control and safety profiles in a population with unique genetic, dietary, and lifestyle factors, which are often underrepresented in global studies. Materials and Procedures: This single-blinded RCT enrolled 112 patients aged 35–65 with HbA1c 7–9%, diabetes >1 year. Patients were randomized into two groups: Group A received Metformin plus Empagliflozin, and Group B received Metformin plus Sitagliptin. Exclusions included irregular medication, prior hypoglycemic use, high creatinine, or glucose-altering drugs. HbA1c was measured monthly; compliance and side effects were monitored. Results: In my research, patients treated with metformin + empagliflozin had a higher likelihood of being in the metformin + empagliflozin group than those treated with metformin + sitagliptin (48.21% vs. 26.79%, respectively) if their HbA1c was under 7%. Side effects with empagliflozin are less than sitagliptin i.e. diarrhea (3.57% vs 8.93%), rash (0.0% vs 5.36%), hypoglycemia (12.50% vs 16.07%), UTI (0.0% vs 7.14%) and increased urination (19.64% vs 10.71%) respectively. Conclusion: When used in conjunction with metformin, SGLT-2 inhibitors are just as safe, effective, and well-tolerated in individuals with Type 2 diabetes mellitus as DPP4 inhibitors.
Downloads
References
Tarhini, Z., Manceur, K., Magne, J., Mathonnet, M., Jost, J., & Christou, N. (2022). The effect of metformin on the survival of colorectal cancer patients with type 2 diabetes mellitus. Scientific Reports, 12(1).
https://doi.org/10.1038/s41598-022-16677-3
LIN, Z. W. (2019). Pioglitazone-metformin and basal insulin for type 2 diabetes mellitus patients with overweight or obesity and poor blood glucose control: A comparison of efficacy and metabolic effects. Academic Journal of Second Military Medical University, 1089-1096.
Grammatiki, M., Sagar, R., & Ajjan, R. A. (2021). Metformin: Is it still the first line in type 2 diabetes management algorithm? Current Pharmaceutical Design, 27(8), 1061-1067.
https://doi.org/10.2174/1381612826666201222154616
Vilsbøll, T., Ekholm, E., Johnsson, E., Dronamraju, N., Jabbour, S., & Lind, M. (2019). Dapagliflozin plus Saxagliptin add-on therapy compared with insulin in patients with type 2 diabetes poorly controlled by metformin with or without Sulfonylurea therapy: A randomized clinical trial. Diabetes Care, 42(8), 1464-1472.
https://doi.org/10.2337/dc18-1988
El Shaer, O., Issaa, H., El Falah, A., Abd El Aziz, S., & Salah, R. (2020). Role of dipeptidyl peptidase 4 in type 2 diabe tes mellitus. Benha Journal of Applied Sciences, 5(1), 1-9.
https://doi.org/10.21608/bjas.2020.135406
Shima, K. R., Ota, T., Kato, K., Takeshita, Y., Misu, H., Kaneko, S., & Takamura, T. (2018). Ursodeoxycholic acid potentiates dipeptidyl peptidase-4 inhibitor sitagliptin by enhancing glucagon-like peptide-1 secretion in patients with type 2 diabetes and chronic liver disease: A pilot randomized controlled and add-on study. BMJ Open Diabetes Research & Care, 6(1), e000469.
https://doi.org/10.1136/bmjdrc-2017-000469
Jia, W., Ma, J., Miao, H., Wang, C., Wang, X., Li, Q., ... & Ji, L. (2021). Chiglitazar monotherapy with sitagliptin as an active comparator in patients with type 2 diabetes: a randomized, double-blind, phase 3 trial (CMAS). Science bulletin, 66(15), 1581-1590.
https://doi.org/10.1016/j.scib.2021.02.027
Scheen, A. (2020). Reduction in HbA1c with SGLT2 inhibitors vs. DPP-4 inhibitors as add-ons to metformin monotherapy according to baseline HbA1c: A systematic review of randomized controlled trials. Diabetes & Metabolism, 46(3), 186-196.
https://doi.org/10.1016/j.diabet.2020.01.002
Trueck, C., Hsin, C., Scherf‐Clavel, O., Schaeffeler, E., Lenssen, R., Gazzaz, M., Gersie, M., Taubert, M., Quasdorff, M., Schwab, M., Kinzig, M., Sörgel, F., Stoffel, M. S., & Fuhr, U. (2019). A clinical drug‐drug interaction study assessing a novel drug transporter Phenotyping cocktail with Adefovir, Sitagliptin, metformin, Pitavastatin, and digoxin. Clinical Pharmacology & Therapeutics, 106(6), 1398-1407.
https://doi.org/10.1002/cpt.1564
Zakaraia, H. G., Salem, H. F., Mostafa, M. A., Ali, A. M., & Rabea, H. M. (2023). Empagliflozin versus Sitagliptin as add-on dual therapy in Egyptian patients with type 2 diabetes inadequately controlled with metformin: A 12-week randomized, open-label, parallel-group trial. Beni-Suef University Journal of Basic and Applied Sciences, 12(1).
https://doi.org/10.1186/s43088-023-00442-0
Ahmed, I., Raja, U. Y., Wahab, M. U., Rehman, T., Ishtiaq, O., Aamir, A. H., Ghaffar, T., Raza, A., Kumar, S., Sherin, A., Masood, F., Randhawa, F. A., Asghar, A., & Khan, S. (2022). Efficacy and safety of combination of empagliflozin and metformin with combination of sitagliptin and metformin during Ramadan: An observational study. BMC Endocrine Disorders, 22(1).
https://doi.org/10.1186/s12902-022-01168-3
Raja, R., Kumar, V., Khan, M. A., Sayeed, K. A., Hussain, S. Z., & Rizwan, A. (2019). Knowledge, attitude, and practices of complementary and alternative medication usage in patients of type II diabetes mellitus. Cureus.
https://doi.org/10.7759/cureus.5357
Sujata, & Thakur, R. (2021). Unequal burden of equal risk factors of diabetes between different gender in India: A cross-sectional analysis. Scientific Reports, 11(1).
https://doi.org/10.1038/s41598-021-02012-9
Maiti, S., Akhtar, S., Upadhyay, A. K., & Mohanty, S. K. (2023). Socioeconomic inequality in awareness, treatment and control of diabetes among adults in India: Evidence from national family health survey of India (NFHS), 2019–2021. Scientific Reports, 13(1).
https://doi.org/10.1038/s41598-023-29978-y
Chaudhary, G. M., Chaudhary, F. M., Tanveer, A., Tameez Ud Din, A., Chaudhary, S. M., Tameez Ud Din, A., & Shafi, A. (2019). Demographic and clinical characteristics of 4556 type 2 diabetes mellitus patients at a tertiary care hospital in southern Punjab. Cureus.
https://doi.org/10.7759/cureus.4592
Khan, P., Qayyum, N., Malik, F., Khan, T., Khan, M., & Tahir, A. (2019). Incidence of anxiety and depression among patients with type 2 diabetes and the predicting factors. Cureus.
https://doi.org/10.7759/cureus.4254
Jatoi, N., Elamin, Y. A., Said, A. H., Al-Namer, B., Al-Muallim, F. A., Al-Nemer, F. F., & Al-Halal, F. M. (2022). Prevalence of cardiovascular risk factors among patients with diabetes mellitus type 2 at King Fahad University hospital, Saudi Arabia. Cureus.
https://doi.org/10.7759/cureus.29489
Bhutto, A. R., Abbasi, A., & Abro, A. H. (2019). Correlation of hemoglobin A1c with red cell width distribution and other parameters of red blood cells in type II diabetes mellitus. Cureus.
https://doi.org/10.7759/cureus.5533
Thomsen, R. W., Knudsen, J. S., Kahlert, J., Baggesen, L. M., Lajer, M., Holmgaard, P. H., Vedin, O., Ustyugova, A., & Sørensen, H. T. (2021). Cardiovascular events, acute hospitalizations, and mortality in patients with type 2 diabetes mellitus who initiate Empagliflozin versus Liraglutide: A comparative effectiveness study. Journal of the American Heart Association, 10(11).
https://doi.org/10.1161/jaha.120.019356
Goldman, J. D. (2018). Combination of Empagliflozin and metformin therapy: A consideration of its place in type 2 diabetes therapy. Clinical Medicine Insights: Endocrinology and Diabetes, 11.
https://doi.org/10.1177/1179551418786258
Scheen, A. J. (2018). The safety of empagliflozin plus metformin for the treatment of type 2 diabetes. Expert Opinion on Drug Safety, 17(8), 837-848.
https://doi.org/10.1080/14740338.2018.1497159
American Diabetes Association. (2018). Cardiovascular disease and risk management: Standards of medical care in diabetes—2018. Diabetes Care, 41, 86–104.
https://doi.org/10.2337/dc18-s009
Hirst, J. A., Farmer, A. J., Ali, R., Roberts, N. W., & Stevens, R. J. (2012). Quantifying the effect of metformin treatment and dose on glycemic control. Diabetes Care, 35(2), 446-454.
https://doi.org/10.2337/dc11-1465
Wan Seman, W. J., Kori, N., Rajoo, S., Othman, H., Mohd Noor, N., Wahab, N. A., Sukor, N., Mustafa, N., & Kamaruddin, N. A. (2016). Switching from sulphonylurea to a sodium‐glucose cotransporter2 inhibitor in the fasting month of Ramadan is associated with a reduction in hypoglycaemia. Diabetes, Obesity and Metabolism, 18(6), 628-632.
https://doi.org/10.1111/dom.12649
Hassanein, M., Echtay, A., Hassoun, A., Alarouj, M., Afandi, B., Poladian, R., Bennakhi, A., Nazar, M., Bergmans, P., Keim, S., Hamilton, G., & Azar, S. T. (2017). Tolerability of canagliflozin in patients with type 2 diabetes mellitus fasting during Ramadan: Results of the Canagliflozin in Ramadan tolerance observational study (CRATOS). International Journal of Clinical Practice, 71(10), e12991.
https://doi.org/10.1111/ijcp.12991
Hassanein, M., Al-Arouj, M., Hamdy, O., Bebakar, W. M., Jabbar, A., Al-Madani, A., Hanif, W., Lessan, N., Basit, A., Tayeb, K., Omar, M., Abdallah, K., Al Twaim, A., Buyukbese, M. A., El-Sayed, A. A., & Ben-Nakhi, A. (2017). Diabetes and Ramadan: Practical guidelines. Diabetes Research and Clinical Practice, 126, 303-316.
https://doi.org/10.1016/j.diabres.2017.03.003
Shao, Y., Lim, G. J., Chua, C. L., Wong, Y. F., Yeoh, E. C., Low, S. K., & Sum, C. F. (2018). The effect of Ramadan fasting and continuing sodium-glucose Co-transporter-2 (SGLT2) inhibitor use on ketonemia, blood pressure and renal function in Muslim patients with type 2 diabetes. Diabetes Research and Clinical Practice, 142, 85-91.
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2025 Indus Journal of Bioscience Research

This work is licensed under a Creative Commons Attribution 4.0 International License.
