<![CDATA[Type 2 DM occurs in approximately 90-95% of total DM cases, antihyperglycemic agents such as GLP-1RA, SGLT2i, DPP-4i, and metformin have been shown to have glycemic control benefits of the four groups which have been confirmed as single administration. in type 2 DM patients, but not yet. neither explains which drug combination has the strongest effect on lowering blood glucose levels. In this study, the effect of both with and without metformin on the blood glucose profile was examined. Animals were induced with lipomed 20% MCT/LCT 20 ml/kg BW for 14 days then continued with a double dose of 35 mg/kg BW streptozotocin. Animals were treated according to the group, negative control and positive control were given 0.5% Na-CMC, empagliflozin (1 mg/kg BW), liraglutide (0.062 mg/kg BW); linagliptin (0.5 mg/kgBW); metformin (87.8 mg/kgBW); combination 1 (0.062 mg/kgBW liraglutide and 1 mg/kgBW empagliflozin); combination 2 (0.5 mg/kgBW linagliptin and 1 mg/kgBW empagliflozin); combination 3 (liraglutide 0.062 mg/kg, empagliflozin 1 mg/kg and metformin 87.8 mg/kg); combination 4 (linagliptin 0.5 mg/kg, empagliflozin 1 mg/kg and metformin 87.8 mg/kg for 30 days. The blood glucose control profile was determined by measuring GDP, administering SGLT-2i, GLP-1RA, DPP-4i, and metformin either alone or in combination can reduce the value of GDP every week. The value of GDP in the SGLT-2i (Empagliflozin) and combination group 1 (Empagliflozin + Liraglutide) can reduce GDP significantly. In improving insulin sensitivity all groups except metformin can significantly increase KITT values. Keywords: Diabetic, empagliflozin, liraglutide, linagliptin, metformin Abstrak DM tipe 2 terjadi pada sekitar 90-95% dari total kasus DM, agen antihiperglikemik seperti GLP-1RA, SGLT2i, DPP-4i dan metformin terbukti memiliki manfaat kontrol glikemik dari keempat golongan tersebut telah terkonfirmasi pemberian tunggalnya pada pasien DM tipe 2, namun belum ada yang menjelaskan kombinasi obat mana yang memiliki efek paling kuat dalam menurunkan kadar glukosa darah. Pada penelitian ini diteliti efek kombinasi keduanya dengan atau tanpa metformin terhadap profil glukosa darah. Hewan diinduksi dengan lipomed 20% MCT/LCT 20 ml/kgBB selama 14 hari kemudian dilanjutkan streptozotocin dosis ganda 35 mg/kg BB. Hewan diberikan perlakuan sesuai kelompok, kontrol negatif dan kontrol positif diberi Na-CMC 0,5%, empagliflozin (1 mg/kgBB), liraglutide (0,062 mg/kg BB); linagliptin (0,5 mg/kgBB); metformin ( 87,8 mg/kgBB); kombinasi 1 (liraglutide 0,062 mg/kgBB dan empagliflozin 1 mg/kgBB); kombinasi 2 (linagliptin 0,5 mg/kgBB dan empagliflozin 1 mg/kgBB); kombinasi 3 (liraglutide 0,062 mg/kgBB, empagliflozin 1 mg/kgBB dan metformin 87,8 mg/kgBB); kombinasi 4 (linagliptin 0,5 mg/kgBB, empagliflozin 1 mg/kgBB dan metformin 87,8 mg/kgBB selama 30 hari. Profil kendali glukosa darah ditentukan melalui pengukuran GDP, pemberian obat golongan SGLT-2i, GLP-1RA, DPP-4i, dan metformin baik tunggal ataupun kombinasinya dapat menurunkan nilai GDP di setiap minggunya. Nilai GDP pada kelompok SGLT-2i (Empagliflozin) dan kombinasi 1 (Empagliflozin+Liraglutide) dapat menurunkan GDP secara signifikan. Pada perbaikan sensitivitas insulin semua kelompok kecuali metformin dapat meningkatkan nilai KITT secara signifikan. Kata Kunci: Diabetes, empagliflozin, liraglutide, linagliptin, metformin]]>
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