PMID- 38253809 OWN - NLM STAT- MEDLINE DCOM- 20240409 LR - 20240415 IS - 1463-1326 (Electronic) IS - 1462-8902 (Linking) VI - 26 IP - 5 DP - 2024 May TI - Glucagon secretion and its association with glycaemic control and ketogenesis during sodium-glucose cotransporter 2 inhibition by ipragliflozin in people with type 1 diabetes: Results from the multicentre, open-label, prospective study. PG - 1605-1614 LID - 10.1111/dom.15458 [doi] AB - AIM: Clinical trials showed the efficacy of sodium-glucose cotransporter 2 inhibitors for type 1 diabetes (T1D) by significant reductions in body weight and glycaemic variability, but elevated susceptibility to ketoacidosis via elevated glucagon secretion was a potential concern. The Suglat-AID evaluated glucagon responses and its associations with glycaemic control and ketogenesis before and after T1D treatment with the sodium-glucose cotransporter 2 inhibitor, ipragliflozin. METHODS: Adults with T1D (n = 25) took 50-mg open-labelled ipragliflozin daily as adjunctive to insulin. Laboratory/clinical data including continuous glucose monitoring were collected until 12 weeks after the ipragliflozin initiation. The participants underwent a mixed-meal tolerance test (MMTT) twice [before (first MMTT) and 12 weeks after ipragliflozin treatment (second MMTT)] to evaluate responses of glucose, C-peptide, glucagon and beta-hydroxybutyrate. RESULTS: The area under the curve from fasting (0 min) to 120 min (AUC(0-120min)) of glucagon in second MMTT were significantly increased by 14% versus first MMTT. The fasting and postprandial beta-hydroxybutyrate levels were significantly elevated in second MMTT versus first MMTT. The positive correlation between postprandial glucagon secretion and glucose excursions observed in first MMTT disappeared in second MMTT, but a negative correlation between fasting glucagon and time below range (glucose, <3.9 mmol/L) appeared in second MMTT. The percentage changes in glucagon levels (fasting and AUC(0-120min)) from baseline to 12 weeks were significantly correlated with those in beta-hydroxybutyrate levels. CONCLUSIONS: Ipragliflozin treatment for T1D increased postprandial glucagon secretion, which did not exacerbate postprandial hyperglycaemia but might protect against hypoglycaemia, leading to reduced glycaemic variability. The increased glucagon secretion might accelerate ketogenesis when adequate insulin is not supplied. CI - (c) 2024 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Nakamura, Yuta AU - Nakamura Y AUID- ORCID: 0000-0003-4950-291X AD - Department of Endocrinology and Metabolism, Division of Advanced Preventive Medical Sciences, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan. FAU - Horie, Ichiro AU - Horie I AUID- ORCID: 0000-0003-3430-5796 AD - Department of Endocrinology and Metabolism, Division of Advanced Preventive Medical Sciences, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan. FAU - Kitamura, Tadahiro AU - Kitamura T AUID- ORCID: 0000-0001-8809-8740 AD - Metabolic Signal Research Center, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi, Japan. FAU - Kusunoki, Yoshiki AU - Kusunoki Y AUID- ORCID: 0000-0002-9361-9317 AD - Department of Diabetes, Endocrinology and Clinical Immunology, Hyogo College of Medicine, Nishinomiya, Japan. FAU - Nishida, Kenro AU - Nishida K AD - Division of Diabetes and Endocrinology, Kumamoto Central Hospital, Kumamoto, Japan. FAU - Yamamoto, Akane AU - Yamamoto A AUID- ORCID: 0009-0002-3672-2809 AD - Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan. FAU - Hirota, Yushi AU - Hirota Y AUID- ORCID: 0000-0002-3035-4155 AD - Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan. FAU - Fukui, Tomoyasu AU - Fukui T AUID- ORCID: 0000-0002-8535-008X AD - Division of Diabetes, Metabolism, and Endocrinology, Department of Medicine, Showa University School of Medicine, Tokyo, Japan. FAU - Maeda, Yasutaka AU - Maeda Y AUID- ORCID: 0000-0002-3259-5622 AD - Minami Diabetes Clinical Research Center, Clinic Masae Minami, Fukuoka, Japan. FAU - Minami, Masae AU - Minami M AD - Minami Diabetes Clinical Research Center, Clinic Masae Minami, Fukuoka, Japan. FAU - Matsui, Takanori AU - Matsui T AUID- ORCID: 0000-0001-9506-7571 AD - Faculty of Bioscience and Biotechnology, Fukui Prefectural University, Fukui, Japan. FAU - Kawakami, Atsushi AU - Kawakami A AD - Department of Endocrinology and Metabolism, Division of Advanced Preventive Medical Sciences, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan. FAU - Abiru, Norio AU - Abiru N AD - Department of Endocrinology and Metabolism, Division of Advanced Preventive Medical Sciences, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan. LA - eng GR - Astellas Pharma Inc./ PT - Journal Article PT - Multicenter Study DEP - 20240122 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - TZP1275679 (3-Hydroxybutyric Acid) RN - 0 (Blood Glucose) RN - 9007-92-5 (Glucagon) RN - IY9XDZ35W2 (Glucose) RN - 0 (Glucosides) RN - 0 (Hypoglycemic Agents) RN - 0 (Insulin) RN - 3N2N8OOR7X (ipragliflozin) RN - 0 (Thiophenes) SB - IM MH - Adult MH - Humans MH - 3-Hydroxybutyric Acid MH - Blood Glucose MH - Blood Glucose Self-Monitoring MH - *Diabetes Mellitus, Type 1/complications/drug therapy MH - *Glucagon/metabolism MH - Glucose MH - *Glucosides MH - Glycemic Control MH - Hypoglycemic Agents/therapeutic use/pharmacology MH - Insulin/therapeutic use MH - Prospective Studies MH - *Thiophenes OTO - NOTNLM OT - SGLT2 OT - glucagon OT - ipragliflozin OT - type 1 diabetes EDAT- 2024/01/23 00:42 MHDA- 2024/04/09 06:45 CRDT- 2024/01/22 23:50 PHST- 2023/12/27 00:00 [revised] PHST- 2023/11/24 00:00 [received] PHST- 2024/01/04 00:00 [accepted] PHST- 2024/04/09 06:45 [medline] PHST- 2024/01/23 00:42 [pubmed] PHST- 2024/01/22 23:50 [entrez] AID - 10.1111/dom.15458 [doi] PST - ppublish SO - Diabetes Obes Metab. 2024 May;26(5):1605-1614. doi: 10.1111/dom.15458. Epub 2024 Jan 22.