PMID- 28786547 OWN - NLM STAT- MEDLINE DCOM- 20181227 LR - 20240315 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 20 IP - 2 DP - 2018 Feb TI - Safety and efficacy of semaglutide once weekly vs sitagliptin once daily, both as monotherapy in Japanese people with type 2 diabetes. PG - 378-388 LID - 10.1111/dom.13082 [doi] AB - AIMS: To assess the safety and efficacy of monotherapy with once-weekly subcutaneous (s.c.) semaglutide vs sitagliptin in Japanese people with type 2 diabetes (T2D). METHODS: In this phase IIIa randomized, open-label, parallel-group, active-controlled, multicentre trial, Japanese adults with T2D treated with diet and exercise only or oral antidiabetic drug monotherapy (washed out during the run-in period) received once-weekly s.c. semaglutide (0.5 or 1.0 mg) or once-daily oral sitagliptin 100 mg. The primary endpoint was number of treatment-emergent adverse events (TEAEs) after 30 weeks. RESULTS: Overall, 308 participants were randomized and exposed to treatment, with similar baseline characteristics across the groups. In total, 2.9% of participants in both the semaglutide 0.5 mg and the sitagliptin group prematurely discontinued treatment, compared with 14.7% in the semaglutide 1.0 mg group. The majority of discontinuations in the semaglutide 0.5 and 1.0 mg groups were attributable to adverse events (AEs). More TEAEs were reported in semaglutide- vs sitagliptin-treated participants (74.8%, 71.6% and 66.0% in the semaglutide 0.5 mg, semaglutide 1.0 mg and sitagliptin groups, respectively). AEs were mainly mild to moderate. Gastrointestinal AEs, most frequently reported with semaglutide, diminished in frequency over time. The mean glycated haemoglobin (HbA1c [baseline 8.1%]) decreased by 1.9% and 2.2% with semaglutide 0.5 and 1.0 mg, respectively, vs 0.7% with sitagliptin (estimated treatment difference [ETD] vs sitagliptin -1.13%, 95% confidence interval [CI] -1.32; -0.94, and -1.44%, 95% CI -1.63; -1.24; both P < .0001). Body weight (baseline 69.3 kg) was reduced by 2.2 and 3.9 kg with semaglutide 0.5 and 1.0 mg, respectively (ETD -2.22 kg, 95% CI -3.02; -1.42 and -3.88 kg, 95% CI -4.70; -3.07; both P < .0001). CONCLUSIONS: In Japanese people with T2D, more TEAEs were reported with semaglutide than with sitagliptin; however, the semaglutide safety profile was similar to that of other glucagon-like peptide-1 receptor agonists. Semaglutide significantly reduced HbA1c and body weight compared with sitagliptin. CI - (c) 2017 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Seino, Yutaka AU - Seino Y AUID- ORCID: 0000-0002-1099-7989 AD - Kansai Electric Power Medical Research Institute, Kobe, Japan. AD - Kansai Electric Power Hospital, Osaka, Japan. FAU - Terauchi, Yasuo AU - Terauchi Y AD - Yokohama City University, Yokohama, Japan. FAU - Osonoi, Takeshi AU - Osonoi T AD - Naka Memorial Clinic, Ibaraki, Japan. FAU - Yabe, Daisuke AU - Yabe D AD - Kansai Electric Power Medical Research Institute, Kobe, Japan. AD - Kansai Electric Power Hospital, Osaka, Japan. AD - Kyoto University, Kyoto, Japan. FAU - Abe, Nobuyuki AU - Abe N AD - Abe Clinic, Oita, Japan. FAU - Nishida, Tomoyuki AU - Nishida T AD - Novo Nordisk Pharma Ltd, Tokyo, Japan. FAU - Zacho, Jeppe AU - Zacho J AD - Novo Nordisk Pharma Ltd, Tokyo, Japan. FAU - Kaneko, Shizuka AU - Kaneko S AD - Takatsuki Red Cross Hospital, Osaka, Japan. LA - eng SI - ClinicalTrials.gov/NCT02254291 PT - Clinical Trial, Phase III PT - Comparative Study PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20171005 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (GLP1R protein, human) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (Glycated Hemoglobin A) RN - 0 (Incretins) RN - 0 (hemoglobin A1c protein, human) RN - 53AXN4NNHX (semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - TS63EW8X6F (Sitagliptin Phosphate) SB - IM MH - Administration, Oral MH - Constipation/chemically induced/physiopathology/therapy MH - Diabetes Mellitus, Type 2/blood/*drug therapy/ethnology MH - Diarrhea/chemically induced/physiopathology/therapy MH - Dipeptidyl-Peptidase IV Inhibitors/administration & dosage/*adverse effects/therapeutic use MH - Dose-Response Relationship, Drug MH - Drug Administration Schedule MH - Follow-Up Studies MH - Glucagon-Like Peptide-1 Receptor/*agonists/metabolism MH - Glucagon-Like Peptides/administration & dosage/*adverse effects/therapeutic use MH - Glycated Hemoglobin/analysis MH - Humans MH - Hyperglycemia/*prevention & control MH - Hypoglycemia/chemically induced/prevention & control MH - Incretins/administration & dosage/*adverse effects/therapeutic use MH - Injections, Subcutaneous MH - Japan MH - Nausea/chemically induced/physiopathology/therapy MH - Patient Dropouts MH - Severity of Illness Index MH - Sitagliptin Phosphate/administration & dosage/*adverse effects/therapeutic use MH - Weight Loss/drug effects PMC - PMC5813234 OTO - NOTNLM OT - GLP-1 OT - sitagliptin OT - type 2 diabetes COIS- Y.S. has received honoraria for consulting and/or speakers bureau from Kao; Kyowa Hakko Kirin; Taisho Pharmaceutical; Becton, Dickinson and Company; Novo Nordisk; MSD; Intarcia Therapeutics; Johnson & Johnson; GlaxoSmithKline; Takeda Pharmaceutical Company; Sanofi; Taisho Toyama Pharmaceutical; Eli Lilly & Company; Mitsubishi Tanabe Pharma; Ono Pharmaceutical; Kowa; Astellas Pharma; Boehringer Ingelheim; AstraZeneca; Sumitomo Dainippon Pharma; Daiichi Sankyo; Terumo; Arkray; and clinical commissioned/joint research grants from Arkray Marketing; Kowa; Hayashibara; Nippon Boehringer Ingelheim; Eli Lilly & Company; Terumo; Taisho Toyama Pharmaceutical; MSD K.K.; Ono Pharmaceutical; Novo Nordisk; Sumitomo Dainippon Pharma; Arklay. Y. T. has received honoraria for speakers bureau from Astellas Pharma; AstraZeneca K.K.; Bayer Yakuhin; Daiichi Sankyo; Sumitomo Dainippon Pharma; Eli Lilly Japan K.K.; Kowa; MSD K.K.; Mitsubishi Tanabe Pharma; Nippon Boehringer Ingelheim; Novo Nordisk; Ono Pharmaceutical; Sanwa Kagaku Kenkyusho; Sanofi K.K.; Shionogi & Company; Taisho Toyama Pharmaceutical; Takeda Pharmaceutical Company; and grants from Astellas Pharma; AstraZeneca K.K.; Bayer Yakuhin; Daiichi Sankyo; Sumitomo Dainippon Pharma; Eli Lilly Japan K.K.; Kowa; MSD K.K.; Mitsubishi Tanabe Pharma; Nippon Boehringer Ingelheim; Novo Nordisk; Ono Pharmaceutical; Pfizer Japan; Sanwa Kagaku Kenkyusho; Sanofi K.K., Shionogi & Company; Takeda Pharmaceutical Company. T. O. is a lecturer and clinical study investigator for Novo Nordisk. D. Y. has received consulting and/or speaker fees from MSD K.K.; Novo Nordisk; Takeda Pharmaceutical Company; Taisho Toyama Pharmaceutical; and clinical commissioned/joint research grants from Nippon Boehringer Ingelheim; Eli Lilly & Company; Taisho Toyama Pharmaceutical; MSD K.K.; Ono Pharmaceutical; Novo Nordisk; Arklay; Takeda Pharmaceutical Company. NA has no conflicts of interest. T.N. is an employee of Novo Nordisk and holds shares in the company. J. Z. is an employee of Novo Nordisk and holds shares in the company. S. K. has received honoraria for speakers bureau from Astellas Pharma; AstraZeneca K.K.; Daiichi Sankyo; Sumitomo Dainippon Pharma; Eli Lilly Japan K.K.; Kissei Pharmaceutical; Mitsubishi Tanabe Pharma; Novo Nordisk; Novartis Pharma K.K.; Ono Pharmaceutical; Sanofi K.K.; Taisho Toyama Pharmaceutical; Takeda Pharmaceutical Company; and grants from WebMD Global LLC. EDAT- 2017/08/09 06:00 MHDA- 2018/12/28 06:00 PMCR- 2018/02/15 CRDT- 2017/08/09 06:00 PHST- 2017/04/13 00:00 [received] PHST- 2017/08/03 00:00 [revised] PHST- 2017/08/04 00:00 [accepted] PHST- 2017/08/09 06:00 [pubmed] PHST- 2018/12/28 06:00 [medline] PHST- 2017/08/09 06:00 [entrez] PHST- 2018/02/15 00:00 [pmc-release] AID - DOM13082 [pii] AID - 10.1111/dom.13082 [doi] PST - ppublish SO - Diabetes Obes Metab. 2018 Feb;20(2):378-388. doi: 10.1111/dom.13082. Epub 2017 Oct 5.