Comparison of Metformin Plus Modified-Release Gliclazide Versus Metformin Plus Sitagliptin in Patients With Type 2 Diabetes Mellitus and Non-Alcoholic Fatty Liver Disease: A Randomized Controlled Trial

Arif Rahim Khan; Shahnawaz Hassan Gardezi; Muhammad Ilyas; Wania Zainab; Muhammad Zulqarnain Haider Khan

doi:10.54112/bcsrj.v7i3.2192

Authors

Arif Rahim Khan Department Of Medicine, Nishtar Hospital, Multan, Pakistan
Shahnawaz Hassan Gardezi Department Of Medicine, Nishtar Hospital, Multan, Pakistan
Muhammad Ilyas Department Of Medicine, Nishtar Hospital, Multan, Pakistan
Wania Zainab Wah Medical College, Wah Cantt, Pakistan
Muhammad Zulqarnain Haider Khan Department Of Medicine, Nishtar Hospital, Multan, Pakistan

DOI:

https://doi.org/10.54112/bcsrj.v7i3.2192

Keywords:

Metformin, Modified-Release Gliclazide, Sitagliptin, Diabetes

Abstract

Type 2 diabetes mellitus (T2DM) commonly coexists with non-alcoholic fatty liver disease (NAFLD), which may complicate glycemic control and therapeutic decision-making. After inadequate response to metformin, sulfonylureas and dipeptidyl peptidase-4 inhibitors are frequently used as add-on therapies. Objective: To compare mean glycated hemoglobin (HbA1c) levels after 12 weeks of treatment with metformin plus modified-release (MR) gliclazide versus metformin plus sitagliptin in patients with T2DM and NAFLD. Methods: This randomized controlled trial included 90 patients with T2DM and NAFLD, who were randomly assigned to two groups. Group A received metformin plus MR gliclazide, while Group B received metformin plus sitagliptin for 12 weeks. HbA1c levels were measured at baseline and at the end of follow-up. This study was conducted at Nishtar Hospital, Multan, from January 2025 to October 2025. Data were analyzed to compare within-group and between-group changes in HbA1c, with p<0.05 considered statistically significant. Results: A total of 90 patients were enrolled, with a slight male predominance (55.5%, n=50). The mean age was 48.2 ± 6.4 years in Group A and 47.9 ± 5.9 years in Group B (p=0.81). In Group A, mean HbA1c decreased from 8.12 ± 0.84% at baseline to 6.91 ± 0.73% after 12 weeks, with a mean reduction of 1.21 ± 0.42% (p<0.001). In Group B, mean HbA1c decreased from 8.05 ± 0.79% to 6.87 ± 0.70%, with a mean reduction of 1.18 ± 0.39% (p<0.001). The difference in mean HbA1c reduction between the two groups was not statistically significant (p=0.62). Conclusion: Metformin combined with either MR gliclazide or sitagliptin significantly improved glycemic control in patients with T2DM and NAFLD over 12 weeks. Both regimens demonstrated comparable efficacy, suggesting that treatment choice may be individualized according to patient profile, safety considerations, and cost.

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References

1. Younossi ZM, Henry L. Epidemiology of NAFLD – focus on diabetes. *Diabetes Res Clin Pract.* 2024;210:111648. DOI: https://doi.org/10.1016/j.diabres.2024.111648

2. Cao L, An Y, Liu H, Jiang J, Liu W, Zhou Y, et al. Global epidemiology of type 2 diabetes in patients with NAFLD or MAFLD: a systematic review and meta-analysis. *BMC Med.* 2024;22(1):101. DOI: https://doi.org/10.1186/s12916-024-03315-0

3. Ajmera V, Cepin S, Tesfai K, Bettencourt R, Noureddin M, Richmond E, et al. A prospective study on the prevalence of NAFLD, advanced fibrosis, cirrhosis, and hepatocellular carcinoma in people with type 2 diabetes. *J Hepatol.* 2023;78(3):471-478. DOI: https://doi.org/10.1016/j.jhep.2022.11.010

4. Zachou M, Flevari P, Nasiri-Ansari N, Varytimiadis C, Kalaitzakis E, Kassi E, et al. The role of anti-diabetic drugs in NAFLD: have we found the Holy Grail? A narrative review. *Eur J Clin Pharmacol.* 2024;80(1):127-150. DOI: https://doi.org/10.1007/s00228-023-03586-1

5. Hassan F, Farman M, Khan KA, Awais M, Akhtar S. Prevalence of nonalcoholic fatty liver disease in Pakistan: a systematic review and meta-analysis. *Sci Rep.* 2024;14(1):19573. DOI: https://doi.org/10.1038/s41598-024-70481-9

6. Memon HL, Farooq S, Aslam M, Saeed A, Batavia A, Sheikh AB, et al. Fatty liver disease in the diabetic population: a cross-sectional study from Pakistan. *Cureus.* 2025;17(6):e85510.

7. Scheen AJ. Comparative effects between old and new antidiabetic agents on metabolic-associated fatty liver disease (MAFLD). *Diabetes Epidemiol Manag.* 2023;11:100145. DOI: https://doi.org/10.1016/j.deman.2023.100145

8. Ko Y, Hayashi S, Shibata M, Hasegawa S, Horiuchi M, Nakano C, et al. Comparison of the efficacy of dipeptidyl peptidase-4 inhibitors and sodium-glucose cotransporter-2 inhibitors in diabetic patients with steatotic liver disease. *Gut Liver.* 2025;19(5):758-766. DOI: https://doi.org/10.5009/gnl240616

9. Yaribeygi H, Ramezani M, Katsiki N, Mirmohammadkhani M, Tabaei NS. Efficacy of adding sitagliptin to ongoing metformin on metabolic profile, triglyceride-glucose index, vitamin D3, and liver tests in patients with type 2 diabetes mellitus and nonalcoholic fatty liver disease: a double-blind randomized clinical trial. *Curr Ther Res Clin Exp.* 2024;101:100764. DOI: https://doi.org/10.1016/j.curtheres.2024.100764

10. Jeon WK, Kang JH, Kim HS. Cardiovascular outcomes comparison of dipeptidyl peptidase-4 inhibitors versus sulfonylurea as add-on therapy for type 2 diabetes mellitus: a meta-analysis. *J Lipid Atheroscler.* 2022;11(1):89-100. DOI: https://doi.org/10.12997/jla.2022.11.1.89

11. Qin M, Chao L, Liu S. Comparative efficacy and safety of sitagliptin or gliclazide combined with metformin in treatment-naive patients with type 2 diabetes: a single-center, prospective, randomized, controlled, noninferiority study with genetic polymorphism analysis. *Medicine (Baltimore).* 2025;104(2):e41061. DOI: https://doi.org/10.1097/MD.0000000000041061

12. Shao X, You J, Zhang H, Jiang X. Comparison of the efficacy of antidiabetic agents in type 2 diabetes with MASLD: a network meta-analysis. *Front Endocrinol (Lausanne).* 2026;16:1659740. DOI: https://doi.org/10.3389/fendo.2025.1659740

13. Doustmohammadian A, Nezhadi A, Rahbariasr F, Tanha K, Hedayat A, Poustchi H, et al. A randomized triple-blind controlled clinical trial evaluation of sitagliptin in the treatment of patients with non-alcoholic fatty liver disease without diabetes. *Front Med (Lausanne).* 2022;9:937554. DOI: https://doi.org/10.3389/fmed.2022.937554

14. Sahin I, Tuncer FF, Aslan AF, Imprialos KP, Rizzo M, Kaze AD, et al. Current position of gliclazide and sulfonylureas in the management of type 2 diabetes: a scoping review. *Diabetes Ther.* 2024;15(8):1669-1710. DOI: https://doi.org/10.1007/s13300-024-01612-8

15. Zou CY, Sun Y, Liang J. Comparative efficacy of diabetes medications on liver enzymes and fat fraction in patients with nonalcoholic fatty liver disease: a network meta-analysis. *Clin Res Hepatol Gastroenterol.* 2023;47(1):102053. DOI: https://doi.org/10.1016/j.clinre.2022.102053

16. Hong JH, Chung ST, Kim KM, Moon JS, Seong K, Lim S, et al. Comparison of therapeutic efficacy and safety of sitagliptin, dapagliflozin, or lobeglitazone adjunct therapy in patients with type 2 diabetes inadequately controlled on sulfonylurea and metformin: third agent study. *Diabetes Res Clin Pract.* 2023;203:110872. DOI: https://doi.org/10.1016/j.diabres.2023.110872