Effectiveness of Combination Oral Antidiabetic Drugs and Their Impact on Clinical Outcomes in Type 2 Diabetes Mellitus Patients Using Systematic Literature Review and Meta-Analysis Method
Main Article Content
Type 2 diabetes mellitus (T2DM) is a metabolic disease characterized by elevated blood sugar levels due to reduced insulin secretion or progressive dysfunction of pancreatic ?-cells, necessitating the use of combination antidiabetic drugs to optimize treatment. This study aims to evaluate the difference in the effectiveness of combination therapies (Metformin plus Sitagliptin vs. Metformin plus Glimepiride) on clinical outcomes in T2DM patients using a systematic literature review and meta-analysis. The research design is quantitative, following a systematic review methodology. A total of 475 articles were initially screened according to inclusion and exclusion criteria, with 5 articles ultimately selected for meta-analysis using a random-effects model. In this systematic review, the results showed that the Metformin plus Sitagliptin group demonstrated better reductions in HbA1c, while the Metformin plus Glimepiride group was more effective in controlling fasting blood sugar (GDP) and postprandial glucose (GDPP). Additionally, the Metformin plus Sitagliptin group was associated with more significant reductions in body weight and BMI. These findings provide insight into treatment decisions for managing T2DM, suggesting that specific combination therapies may be more effective for particular clinical outcomes. Defining acronyms such as GDP and GDPP within the abstract ensures clarity for readers unfamiliar with these terms.
Keywords:
Oral Antidiabetic combination, Effectiveness, Metformin plus Sitaglipin and Metformin plus Glimepiride, HbA1c, GDP, GDPP
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Bianchi, C., Daniele, G., Dardano, A., Miccoli, R., & Del Prato, S. (2017). Early combination therapy with oral glucose-lowering agents in type 2 diabetes. Drugs, 77, 247–264.
Blahova, J., Martiniakova, M., Babikova, M., Kovacova, V., Mondockova, V., & Omelka, R. (2021). Pharmaceutical drugs and natural therapeutic products for the treatment of type 2 diabetes mellitus. Pharmaceuticals, 14(8), 806.
Chan, J. C. N., Aschner, P., Owens, D. R., Picard, S., Vincent, M., Dain, M.-P., Pilorget, V., Loizeau, V., Echtay, A., & Fonseca, V. (2015). Triple combination of insulin glargine, sitagliptin and metformin in type 2 diabetes: The EASIE post-hoc analysis and extension trial. Journal of Diabetes and Its Complications, 29(1), 134–141. https://doi.org/10.1016/j.jdiacomp.2014.08.007
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Cheekireddy, V. M., Himaja, D., & Teja, Y. D. (2016). Safety, Efficacy and Bioavailability of Fixed Dose Combinations in Type 2 Diabetes Mellitus: A Systematic Updated Review.
Devarajan, T. V, Venkataraman, S., Kandasamy, N., Oomman, A., Boorugu, H. K., Karuppiah, S. K. P., & Balat, D. (2017). Comparative evaluation of safety and efficacy of glimepiride and sitagliptin in combination with metformin in patients with type 2 diabetes mellitus: Indian multicentric randomized trial-START study. Indian Journal of Endocrinology and Metabolism, 21(5), 745–750.
Gupta, S., Khajuria, V., Tandon, V. R., Mahajan, A., & Gillani, Z. H. (2015). Comparative evaluation of efficacy and safety of combination of metformin-vidagliptin versus metfromin-glimepiride in most frequently used doses in patients of type 2 diabetes mellitus with inadequately controlled metformin monotherapy-A randomised open label study. Perspectives in Clinical Research, 6(3), 163–168.
Kautzky-Willer, A., Harreiter, J., & Pacini, G. (2016). Sex and gender differences in risk, pathophysiology and complications of type 2 diabetes mellitus. Endocrine Reviews, 37(3), 278–316.
Khairinnisa, A., Yusmaini, H., & Hadiwiardjo, Y. H. (2020a). Perbandingan Penggunaan Glibenclamid-Metformin dan Glimepirid-Metformin Terhadap Efek Samping Hipoglikemia Pasien Diabetes Melitus Tipe-2 di Kota Tangerang Selatan Bulan Januari–Oktober Tahun 2019. Seminar Nasional Riset Kedokteran, 1(1).
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Kristin, E. (2016). Dipeptidyl peptidase 4 (DPP-4) inhibitors for the treatment of type 2 diabetes mellitus. Journal of Medical Sciences, 48(2), 1–9.
Kumar, S., Pathak, A. K., Saikia, D., & Kumar, A. (2015). Efficacy, safety and treatment satisfaction of glimepiride vs sitagliptin in combination with metformin in type 2 diabetes mellitus. Journal of Clinical and Diagnostic Research: JCDR, 9(12), FC07.
Lundby-Christensen, L., Tarnow, L., Boesgaard, T. W., Lund, S. S., Wiinberg, N., Perrild, H., Krarup, T., Snorgaard, O., Gade-Rasmussen, B., & Thorsteinsson, B. (2016). Metformin versus placebo in combination with insulin analogues in patients with type 2 diabetes mellitus—the randomised, blinded Copenhagen Insulin and Metformin Therapy (CIMT) trial. BMJ Open, 6(2), e008376.
Ogurtsova, K., da Rocha Fernandes, J. D., Huang, Y., Linnenkamp, U., Guariguata, L., Cho, N. H., Cavan, D., Shaw, J. E., & Makaroff, L. E. (2017). IDF Diabetes Atlas: Global estimates for the prevalence of diabetes for 2015 and 2040. Diabetes Research and Clinical Practice, 128, 40–50. https://doi.org/10.1016/j.diabres.2017.03.024
Rados, D. V., Pinto, L. C., Remonti, L. R., Leitao, C. B., & Gross, J. L. (2016). The association between sulfonylurea use and all-cause and cardiovascular mortality: a meta-analysis with trial sequential analysis of randomized clinical trials. PLoS Medicine, 13(4), e1001992.
Ratnasari, N. L. M. N., & Bhargah, A. (2018). Pola penggunaan insulin pada pasien diabetes mellitus tipe 2 di poli penyakit dalam RSU Negara Periode Juli-Agustus 2018. Intisari Sains Medis, 9(3).
Sani, S., Akhtar, M. S., Kapur, P., Sharma, G., Tabassum, F., Khan, M. F., & Sharma, M. (2022a). Evaluation of Prescribing Pattern, Therapeutic Adherence and Occurrence of Adverse Drug Reactions in Patients with Type 2 Diabetes Mellitus. Current Drug Therapy, 17(3), 177–185.
Sani, S., Akhtar, M. S., Kapur, P., Sharma, G., Tabassum, F., Khan, M. F., & Sharma, M. (2022b). Evaluation of Prescribing Pattern, Therapeutic Adherence and Occurrence of Adverse Drug Reactions in Patients with Type 2 Diabetes Mellitus. Current Drug Therapy, 17(3), 177–185.
Sharma, M., Sonawane, R., & Marko, J. L. (2016). Comparative study of efficacy and safety of sitagliptin versus glimepiride in patients of type-2 diabetes mellitus inadequately controlled with metformin alone. Int J Adv Med, 3, 564–568.
Sharma, S., Sharma, P., & Sharma, M. (2018). Comparative study of efficacy and safety of sitagliptin in comparison with glimepiride in treatment of type 2 diabetes mellitus. International Journal of Medicine Research, 3(2), 56–60.
Shin, S., & Kim, H. (2016). The effect of sitagliptin on cardiovascular risk profile in Korean patients with type 2 diabetes mellitus: a retrospective cohort study. Therapeutics and Clinical Risk Management, 435–444.
Sihotang, R. C., Ramadhani, R., & Tahapary, D. L. (2018). Efikasi dan keamanan obat anti diabetik oral pada pasien diabetes melitus tipe 2 dengan penyakit ginjal kronik. Jurnal Penyakit Dalam Indonesia| Vol, 5(3).
Sudikno, S., Syarief, H., Dwiriani, C. M., & Riyadi, H. (2015). Faktor risiko obesitas sentral pada orang dewasa umur 25-65 tahun di Indonesia (Analisis data Riset Kesehatan Dasar 2013).
Varela-Fernández, R., Díaz-Tomé, V., Luaces-Rodríguez, A., Conde-Penedo, A., García-Otero, X., Luzardo-Álvarez, A., Fernández-Ferreiro, A., & Otero-Espinar, F. J. (2020). Drug delivery to the posterior segment of the eye: biopharmaceutic and pharmacokinetic considerations. Pharmaceutics, 12(3), 269.
Vijayakumar, T. M., Jayram, J., Meghana Cheekireddy, V., Himaja, D., Dharma Teja, Y., & Narayanasamy, D. (2017). Safety, Efficacy, and Bioavailability of Fixed-Dose Combinations in Type 2 Diabetes Mellitus: A Systematic Updated Review. Current Therapeutic Research, 84, 4–9. https://doi.org/10.1016/j.curtheres.2017.01.005
Wijaya, I., PD, S., & Kes, M. (2015). Manfaat kombinasi glimepirid dan metformin pada tatalaksana DM tipe 2’. Farmasi Dan Ilmu Kesehatan, 3–7.
Yasa, P. M., & Putere, S. P. M. (2020). Difference in Effectiveness of Metformin and Gliclazide for Reducing Blood Glucose in Outpatients with Type 2 Diabetes Mellitus in Sanjiwani Hospital. The Proceedings of the 1st Seminar The Emerging of Novel Corona Virus, NCov 2020, 11-12 February 2020, Bali, Indonesia.
Yosmar, R., Almasdy, D., & Rahma, F. (2018). Survei risiko penyakit diabetes melitus terhadap masyarakat Kota Padang. JSFK (Jurnal Sains Farmasi & Klinis), 5(2), 134–141.
Amate, J. M., Lopez?Cuadrado, T., Almendro, N., Bouza, C., Saz?Parkinson, Z., Rivas?Ruiz, R., & Gonzalez?Canudas, J. (2015). Effectiveness and safety of glimepiride and iDPP4, associated with metformin in second line pharmacotherapy of type 2 diabetes mellitus: systematic review and meta?analysis. International Journal of Clinical Practice, 69(3), 292–304.
Association, A. D. (2014). Standards of medical care in diabetes—2014. Diabetes Care, 37(Supplement_1), S14–S80.
Bianchi, C., Daniele, G., Dardano, A., Miccoli, R., & Del Prato, S. (2017). Early combination therapy with oral glucose-lowering agents in type 2 diabetes. Drugs, 77, 247–264.
Blahova, J., Martiniakova, M., Babikova, M., Kovacova, V., Mondockova, V., & Omelka, R. (2021). Pharmaceutical drugs and natural therapeutic products for the treatment of type 2 diabetes mellitus. Pharmaceuticals, 14(8), 806.
Chan, J. C. N., Aschner, P., Owens, D. R., Picard, S., Vincent, M., Dain, M.-P., Pilorget, V., Loizeau, V., Echtay, A., & Fonseca, V. (2015). Triple combination of insulin glargine, sitagliptin and metformin in type 2 diabetes: The EASIE post-hoc analysis and extension trial. Journal of Diabetes and Its Complications, 29(1), 134–141. https://doi.org/10.1016/j.jdiacomp.2014.08.007
Chatterjee, M., Sharma, T., Sharma, A., & Kalra, J. (2017). Comparison of the efficacy and safety of Glimepiride and Glipizide as add-on therapy with metformin in patients of type 2 diabetes mellitus. International Journal of Basic & Clinical Pharmacology, 6(3), 675.
Cheekireddy, V. M., Himaja, D., & Teja, Y. D. (2016). Safety, Efficacy and Bioavailability of Fixed Dose Combinations in Type 2 Diabetes Mellitus: A Systematic Updated Review.
Devarajan, T. V, Venkataraman, S., Kandasamy, N., Oomman, A., Boorugu, H. K., Karuppiah, S. K. P., & Balat, D. (2017). Comparative evaluation of safety and efficacy of glimepiride and sitagliptin in combination with metformin in patients with type 2 diabetes mellitus: Indian multicentric randomized trial-START study. Indian Journal of Endocrinology and Metabolism, 21(5), 745–750.
Gupta, S., Khajuria, V., Tandon, V. R., Mahajan, A., & Gillani, Z. H. (2015). Comparative evaluation of efficacy and safety of combination of metformin-vidagliptin versus metfromin-glimepiride in most frequently used doses in patients of type 2 diabetes mellitus with inadequately controlled metformin monotherapy-A randomised open label study. Perspectives in Clinical Research, 6(3), 163–168.
Kautzky-Willer, A., Harreiter, J., & Pacini, G. (2016). Sex and gender differences in risk, pathophysiology and complications of type 2 diabetes mellitus. Endocrine Reviews, 37(3), 278–316.
Khairinnisa, A., Yusmaini, H., & Hadiwiardjo, Y. H. (2020a). Perbandingan Penggunaan Glibenclamid-Metformin dan Glimepirid-Metformin Terhadap Efek Samping Hipoglikemia Pasien Diabetes Melitus Tipe-2 di Kota Tangerang Selatan Bulan Januari–Oktober Tahun 2019. Seminar Nasional Riset Kedokteran, 1(1).
Khairinnisa, A., Yusmaini, H., & Hadiwiardjo, Y. H. (2020b). Perbandingan Penggunaan Glibenclamid-Metformin dan Glimepirid-Metformin Terhadap Efek Samping Hipoglikemia Pasien Diabetes Melitus Tipe-2 di Kota Tangerang Selatan Bulan Januari–Oktober Tahun 2019. Seminar Nasional Riset Kedokteran, 1(1).
Komariah, K., & Rahayu, S. (2020). Hubungan usia, jenis kelamin dan indeks massa tubuh dengan kadar gula darah puasa pada pasien diabetes melitus tipe 2 di klinik pratama rawat jalan proklamasi, Depok, Jawa Barat. Jurnal Kesehatan Kusuma Husada, 41–50.
Kristin, E. (2016). Dipeptidyl peptidase 4 (DPP-4) inhibitors for the treatment of type 2 diabetes mellitus. Journal of Medical Sciences, 48(2), 1–9.
Kumar, S., Pathak, A. K., Saikia, D., & Kumar, A. (2015). Efficacy, safety and treatment satisfaction of glimepiride vs sitagliptin in combination with metformin in type 2 diabetes mellitus. Journal of Clinical and Diagnostic Research: JCDR, 9(12), FC07.
Lundby-Christensen, L., Tarnow, L., Boesgaard, T. W., Lund, S. S., Wiinberg, N., Perrild, H., Krarup, T., Snorgaard, O., Gade-Rasmussen, B., & Thorsteinsson, B. (2016). Metformin versus placebo in combination with insulin analogues in patients with type 2 diabetes mellitus—the randomised, blinded Copenhagen Insulin and Metformin Therapy (CIMT) trial. BMJ Open, 6(2), e008376.
Ogurtsova, K., da Rocha Fernandes, J. D., Huang, Y., Linnenkamp, U., Guariguata, L., Cho, N. H., Cavan, D., Shaw, J. E., & Makaroff, L. E. (2017). IDF Diabetes Atlas: Global estimates for the prevalence of diabetes for 2015 and 2040. Diabetes Research and Clinical Practice, 128, 40–50. https://doi.org/10.1016/j.diabres.2017.03.024
Rados, D. V., Pinto, L. C., Remonti, L. R., Leitao, C. B., & Gross, J. L. (2016). The association between sulfonylurea use and all-cause and cardiovascular mortality: a meta-analysis with trial sequential analysis of randomized clinical trials. PLoS Medicine, 13(4), e1001992.
Ratnasari, N. L. M. N., & Bhargah, A. (2018). Pola penggunaan insulin pada pasien diabetes mellitus tipe 2 di poli penyakit dalam RSU Negara Periode Juli-Agustus 2018. Intisari Sains Medis, 9(3).
Sani, S., Akhtar, M. S., Kapur, P., Sharma, G., Tabassum, F., Khan, M. F., & Sharma, M. (2022a). Evaluation of Prescribing Pattern, Therapeutic Adherence and Occurrence of Adverse Drug Reactions in Patients with Type 2 Diabetes Mellitus. Current Drug Therapy, 17(3), 177–185.
Sani, S., Akhtar, M. S., Kapur, P., Sharma, G., Tabassum, F., Khan, M. F., & Sharma, M. (2022b). Evaluation of Prescribing Pattern, Therapeutic Adherence and Occurrence of Adverse Drug Reactions in Patients with Type 2 Diabetes Mellitus. Current Drug Therapy, 17(3), 177–185.
Sharma, M., Sonawane, R., & Marko, J. L. (2016). Comparative study of efficacy and safety of sitagliptin versus glimepiride in patients of type-2 diabetes mellitus inadequately controlled with metformin alone. Int J Adv Med, 3, 564–568.
Sharma, S., Sharma, P., & Sharma, M. (2018). Comparative study of efficacy and safety of sitagliptin in comparison with glimepiride in treatment of type 2 diabetes mellitus. International Journal of Medicine Research, 3(2), 56–60.
Shin, S., & Kim, H. (2016). The effect of sitagliptin on cardiovascular risk profile in Korean patients with type 2 diabetes mellitus: a retrospective cohort study. Therapeutics and Clinical Risk Management, 435–444.
Sihotang, R. C., Ramadhani, R., & Tahapary, D. L. (2018). Efikasi dan keamanan obat anti diabetik oral pada pasien diabetes melitus tipe 2 dengan penyakit ginjal kronik. Jurnal Penyakit Dalam Indonesia| Vol, 5(3).
Sudikno, S., Syarief, H., Dwiriani, C. M., & Riyadi, H. (2015). Faktor risiko obesitas sentral pada orang dewasa umur 25-65 tahun di Indonesia (Analisis data Riset Kesehatan Dasar 2013).
Varela-Fernández, R., Díaz-Tomé, V., Luaces-Rodríguez, A., Conde-Penedo, A., García-Otero, X., Luzardo-Álvarez, A., Fernández-Ferreiro, A., & Otero-Espinar, F. J. (2020). Drug delivery to the posterior segment of the eye: biopharmaceutic and pharmacokinetic considerations. Pharmaceutics, 12(3), 269.
Vijayakumar, T. M., Jayram, J., Meghana Cheekireddy, V., Himaja, D., Dharma Teja, Y., & Narayanasamy, D. (2017). Safety, Efficacy, and Bioavailability of Fixed-Dose Combinations in Type 2 Diabetes Mellitus: A Systematic Updated Review. Current Therapeutic Research, 84, 4–9. https://doi.org/10.1016/j.curtheres.2017.01.005
Wijaya, I., PD, S., & Kes, M. (2015). Manfaat kombinasi glimepirid dan metformin pada tatalaksana DM tipe 2’. Farmasi Dan Ilmu Kesehatan, 3–7.
Yasa, P. M., & Putere, S. P. M. (2020). Difference in Effectiveness of Metformin and Gliclazide for Reducing Blood Glucose in Outpatients with Type 2 Diabetes Mellitus in Sanjiwani Hospital. The Proceedings of the 1st Seminar The Emerging of Novel Corona Virus, NCov 2020, 11-12 February 2020, Bali, Indonesia.
Yosmar, R., Almasdy, D., & Rahma, F. (2018). Survei risiko penyakit diabetes melitus terhadap masyarakat Kota Padang. JSFK (Jurnal Sains Farmasi & Klinis), 5(2), 134–141.
