DIPEPTIDYL PEPTIDASE 4 (DPP-4) INHIBITORS FOR THE TREATMENT OF TYPE 2 DIABETES MELLITUS

ABSTRACT Diabetes mellitus (DM) is a chronic disease which caused around 1.5 million deaths in 2012 according to the World Health Organization. Type 2 diabetes mellitus (T2DM) accounts for 90% of DM worldwide. The prevalence of T2DM is increasing due to obesity. Clinical guidelines recommend the use of metformin as the first-line treatment unless contraindicated, followed by the addition of 1 or 2 OADs, such as sulphonylurea (SU), an alpha-glucosidase inhibitor, or thiazolidinediones (TZDs). Recently, newer agents such as dipeptidyl peptidase 4 (DPP-4) inhibitors have been added to those treatment algorithms. The DPP-4 inhibitor is a class of oral antidiabetic drug that inhibits the DPP-4 enzyme. Sitagliptin, saxagliptin, vildagliptin and linagliptin are dipeptidyl peptidase-4 (DPP-4) inhibitors available for the treatment of type 2 diabetes in Indonesia and many other countries. DPP-4 inhibitors have similar glycemic efficacy. They produce a moderate improvement in glycated hemoglobin (A1C). However, there are limited numbers of head-to-head trials, and there are no data on the use of long-term use (more than two years) safety, mortality, diabetic complications, or health-related quality of life. Although DPP-inhibitors are not used as initial treatment for a majority of patients with type 2 diabetes, DPP-4 inhibitors can be used as add-on therapy in type 2 diabetes patients who are intolerant to, have contraindications for, or uncontrolled with the use of metformin, sulphonylureas, or thiazolidinediones. The true role of DPP-4 inhibitors among several other agents to manage type 2 diabetes is not clear. There were only a small number of long-term studies on DPP-4 inhibitors assessing the glycemic decrease efficacy, important clinical outcomes (cardiovascular events, mortality), or safety. In patients with chronic renal failure (estimated glomerular filtration rate [eGFR] < 30 mL/min) considered to use DPP-4 inhibitors, linagliptin can be chosen. Overall, DPP-4 inhibitors are well-tolerated. There are inadequate data to assess the effect of DPP-4 inhibitors on the occurrence of acute pancreatitis. ABSTRAK Diabetes mellitus (DM) merupakan penyakit kronis yang menyebabkan sekitar 1,5 juta kematian pada tahun 2012 menurut Organisasi Kesehatan Dunia (WHO). DM tipe 2 (DMT2) banyaknya 90% dari keseluruhan DM di seluruh dunia. Prevalensi DMT2 meningkat karena obesitas. Pedoman klinis merekomendasikan penggunaan metformin sebagai pengobatan lini pertama kecuali ada kontraindikasi, maka bisa diikuti dengan penambahan 1 atau 2 OADs, seperti sulfonilurea (SU), inhibitor alpha-glucosidase, atau thiazolidinediones (TZD). Baru-baru ini, obat baru golongan dipeptidyl peptidase 4 (DPP-4) inhibitor telah ditambahkan ke algoritma pengobatan. Dipeptidyl peptidase 4 (DPP-4) inhibitor inhibitor adalah kelas obat antidiabetes oral yang menghambat DPP-4 enzim. Sitagliptin, saxagliptin, vildagliptin dan linagliptin yang merupakan golongan dipeptidyl peptidase-4 (DPP-4) inhibitor tersedia untuk pengobatan diabetes tipe 2 di Indonesia dan banyak negara lainnya. DPP-4 inhibitor memiliki khasiat glikemik yang setara. DPP-4 inhibitor menghasilkan peningkatan moderat hemoglobin terglikasi (A1C). Namun uji coba head-to-head jumlahnya terbatas, dan tidak ada data tentang penggunaan penggunaan jangka panjang (lebih dari dua tahun) keamanan, kematian, komplikasi diabetes, atau kualitas-hidup pasien. Meskipun DPP-inhibitor tidak digunakan sebagai terapi awal untuk mayoritas pasien dengan diabetes tipe 2, DPP-4 inhibitor dapat digunakan sebagai terapi tambahan di tipe 2 pasien diabetes yang tidak toleran, ada kontraindikasi, atau tidak terkontrol dengan penggunaan metformin, sulfonilurea, atau thiazolidinediones. Peran sebenarnya dari DPP-4 inhibitor di antara beberapa obat lainnya untuk DMT2 tidak begitu jelas. Hanya ada sejumlah kecil studi jangka panjang pada DPP-4 inhibitor menilai penurunan glikemik, kemanjuran, kejadian kardiovaskular, kematian, atau keamanan. Pada pasien dengan gagal ginjal (perkiraan laju filtrasi glomerulus [eGFR]