title: Incretin-based drugs for type 2 diabetes: Focus on East Asian perspectives.
abstract: Type 2 diabetes in East Asians is characterized primarily by β-cell dysfunction, and with less adiposity and less insulin resistance compared with that in Caucasians. Such pathophysiological differences can determine the appropriate therapeutics for the disease. Incretins, glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1, are secreted in response to meal ingestion, and enhance insulin secretion glucose-dependently. Incretin-based drugs, dipeptidyl peptidase-4 inhibitors (DPP-4i) and glucagon-like peptide-1 receptor agonists, that ameliorate β-cell dysfunction with limited hypoglycemia risk are now widely used in type 2 diabetes management. Recent meta-analyses of clinical trials on DPP-4i and glucagon-like peptide-1 receptor agonists found that the drugs were more effective in Asians, most likely because of amelioration of β-cell dysfunction. In addition, we found increased glycated hemoglobin-lowering effects of DPP-4i to be associated with intake of fish in type 2 diabetes, which suggests that dietary customs of East Asians might also underlie the greater efficacy of DPP-4i. Despite the limited risk, cases of severe hypoglycemia were reported for DPP-4i/sulfonylureas combinations. Importantly, hypoglycemia was more frequent in patients also receiving glibenclamide or glimepiride, which activate exchange protein directly activated by cyclic adenosine monophosphate 2, a critical mediator of incretin signaling, and was less frequent in patients receiving gliclazide, which does not activate exchange protein directly activated by cyclic adenosine monophosphate 2. Prevention of insulin-associated hypoglycemia by DPP-4i has gained attention with regard to the enhancement of hypoglycemia-induced glucagon secretion by insulinotropic polypeptide, but remains to be investigated in East Asians. Despite the safety issues, which are paramount and must be carefully monitored, the incretin-based drugs could have potential as a first choice therapy in East Asian type 2 diabetes patients.
authors.affiliation: Yutaka Seino Distinguished Center for Diabetes ResearchKansai Electric Power Medical Research InstituteKobeJapan; Center for Diabetes, Endocrinology and MetabolismKansai Electric Power HospitalOsakaJapan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Seino
authors.affiliation: Yutaka Seino Distinguished Center for Diabetes ResearchKansai Electric Power Medical Research InstituteKobeJapan; Center for Diabetes, Endocrinology and MetabolismKansai Electric Power HospitalOsakaJapan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Kuwata
authors.affiliation: Yutaka Seino Distinguished Center for Diabetes ResearchKansai Electric Power Medical Research InstituteKobeJapan; Center for Diabetes, Endocrinology and MetabolismKansai Electric Power HospitalOsakaJapan; Center for Metabolism and Clinical NutritionKansai Electric Power HospitalOsakaJapan; Division of Molecular and Metabolic MedicineKobe University Graduate School of MedicineKobeJapan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Yabe
mesh_terms: D000818:Animals; D044466:Asian People / Q000208:ethnology; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy* / Q000208:ethnology; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D005947:Glucose / Q000378:metabolism; D005951:Glucose Tolerance Test; D005905:Glyburide / Q000009:adverse effects / Q000627:therapeutic use; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007003:Hypoglycemia / Q000139:chemically induced* / Q000208:ethnology; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D054795:Incretins / Q000009:adverse effects / Q000627:therapeutic use*; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance / Q000208:ethnology; D000078790:Insulin Secretion; D051379:Mice; D051381:Rats; D012307:Risk Factors; D013453:Sulfonylurea Compounds / Q000009:adverse effects / Q000627:therapeutic use; D016896:Treatment Outcome; D000097789:Glucagon-Like Peptide-1 Receptor Agonists
chemical_list: D054873:Dipeptidyl-Peptidase IV Inhibitors; D005947:Glucose; D005905:Glyburide; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D054795:Incretins; D007328:Insulin; D013453:Sulfonylurea Compounds; D000097789:Glucagon-Like Peptide-1 Receptor Agonists; C517652:hemoglobin A1c protein, human; C057619:glimepiride
keywords: Dipeptidyl peptidase‐4 inhibitors; East Asian; Glucagon‐like peptide‐1 receptor agonists