PMID- 29110647 OWN - NLM STAT- MEDLINE DCOM- 20180709 LR - 20240327 IS - 1472-6823 (Electronic) IS - 1472-6823 (Linking) VI - 17 IP - 1 DP - 2017 Nov 6 TI - A randomized, placebo-controlled clinical trial evaluating the safety and efficacy of the once-weekly DPP-4 inhibitor omarigliptin in patients with type 2 diabetes mellitus inadequately controlled by glimepiride and metformin. PG - 70 LID - 10.1186/s12902-017-0219-x [doi] LID - 70 AB - BACKGROUND: Type 2 diabetes (T2D) is a progressive disease that often requires a patient to use multiple antihyperglycemic agents to achieve glycemic control with disease progression. Omarigliptin is a once-weekly dipeptidyl peptidase-4 inhibitor. The purpose of this trial was to assess the efficacy and safety of adding omarigliptin to the treatment regimen of patients with T2D inadequately controlled by dual therapy with metformin and glimepiride. METHODS: Patients with T2D and HbA1c >/=7.5% and /=1500 mg/day) and glimepiride (>/=4 mg/day) were randomized to omarigliptin 25 mg once-weekly (N = 154) or placebo (N = 153) for 24 weeks. The primary objective was to assess whether omarigliptin was superior to placebo in reducing HbA1c at Week 24. Secondary objectives were to assess the effects of omarigliptin vs. placebo on FPG and the proportion of subjects attaining HbA1c goals of <7% and <6.5%. RESULTS: From a mean baseline HbA1c of 8.5% (omarigliptin) and 8.6% (placebo), the least squares (LS) mean change from baseline in HbA1c at Week 24 was -0.67% in the omarigliptin group and -0.06% in the placebo group, with a between-group difference (95% CI) of -0.61% (-0.85, -0.38). Treatment with omarigliptin resulted in a significantly greater reduction in FPG relative to placebo (LS mean difference [95% CI] -0.9 mmol/L [-1.4, -0.4]; p < 0.001). The proportion of patients achieving glycemic goals of <7.0% and <6.5% was higher in the omarigliptin group relative to the placebo group. The overall incidences of adverse events (AEs), serious AEs, drug-related AEs and discontinuations were generally similar between treatment groups. The incidence of symptomatic hypoglycemia was 10.5% in the omarigliptin group and 8.5% in the placebo group. Relative to baseline, omarigliptin and placebo treatments were associated with LS mean changes in body weight of -0.1 kg and -0.9 kg, respectively. CONCLUSION: In patients with T2D and inadequate glycemic control on dual therapy with metformin and glimepiride, compared with placebo, once-weekly omarigliptin provided greater improvement in glycemic control and was generally well tolerated. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01704261 , EudraCT Number: 2012-002612-10. Trial Registration Date: October 8, 2012. FAU - Lee, Seung-Hwan AU - Lee SH AD - Department of Internal Medicine, Division of Endocrinology and Metabolism, Seoul St.Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea. FAU - Gantz, Ira AU - Gantz I AUID- ORCID: 0000-0002-6565-7113 AD - Merck & Co., Inc., 2000 Galloping Hill Road, Kenilworth, NJ, 07033, USA. ira.gantz@merck.com. FAU - Round, Elizabeth AU - Round E AD - Merck & Co., Inc., 2000 Galloping Hill Road, Kenilworth, NJ, 07033, USA. FAU - Latham, Melanie AU - Latham M AD - Merck & Co., Inc., 2000 Galloping Hill Road, Kenilworth, NJ, 07033, USA. FAU - O'Neill, Edward A AU - O'Neill EA AD - Merck & Co., Inc., 2000 Galloping Hill Road, Kenilworth, NJ, 07033, USA. FAU - Ceesay, Paulette AU - Ceesay P AD - Merck & Co., Inc., 2000 Galloping Hill Road, Kenilworth, NJ, 07033, USA. FAU - Suryawanshi, Shailaja AU - Suryawanshi S AD - Merck & Co., Inc., 2000 Galloping Hill Road, Kenilworth, NJ, 07033, USA. FAU - Kaufman, Keith D AU - Kaufman KD AD - Merck & Co., Inc., 2000 Galloping Hill Road, Kenilworth, NJ, 07033, USA. FAU - Engel, Samuel S AU - Engel SS AD - Merck & Co., Inc., 2000 Galloping Hill Road, Kenilworth, NJ, 07033, USA. FAU - Lai, Eseng AU - Lai E AD - Merck & Co., Inc., 2000 Galloping Hill Road, Kenilworth, NJ, 07033, USA. LA - eng SI - ClinicalTrials.gov/NCT01704261 PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial DEP - 20171106 PL - England TA - BMC Endocr Disord JT - BMC endocrine disorders JID - 101088676 RN - 0 (2-(2,5-difluorophenyl)-5-(2-(methylsulfonyl)-2,6-dihydropyrrolo(3,4-c)pyrazol-5(4H)-yl)tetrahydro-2H-pyran-3-amine) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Heterocyclic Compounds, 2-Ring) RN - 0 (Hypoglycemic Agents) RN - 0 (Pyrans) RN - 0 (Sulfonylurea Compounds) RN - 6KY687524K (glimepiride) RN - 9100L32L2N (Metformin) SB - IM MH - Aged MH - Diabetes Mellitus, Type 2/*drug therapy MH - Dipeptidyl-Peptidase IV Inhibitors/*administration & dosage/adverse effects MH - Drug Therapy, Combination MH - Female MH - Heterocyclic Compounds, 2-Ring/*administration & dosage/adverse effects MH - Humans MH - Hypoglycemic Agents/administration & dosage MH - Male MH - Metformin/administration & dosage MH - Middle Aged MH - Pyrans/*administration & dosage/adverse effects MH - Sulfonylurea Compounds/administration & dosage PMC - PMC5674832 OTO - NOTNLM OT - Incretin therapy OT - MK-3102 OT - Oral antihyperglycemic agent COIS- ETHICS APPROVAL AND CONSENT TO PARTICIPATE: The study (MK-3102-022; NCT01704261, EudraCT: 2012-002612-10) was conducted in accordance with the principles of Good Clinical Practice. Independent Ethics Committees (IECs) reviewed and approved the protocol and applicable amendments (see Appendix 1). Written informed consent was obtained from all study participants. CONSENT FOR PUBLICATION: Not applicable. COMPETING INTERESTS: S-HL reports grants and personal fees from Merck during the conduct of the study. S-HL also received grants and/or personal fees from Merck, AstraZeneca, Sanofi Aventis, LG Life Science, Boeringher-Ingelheim, Daewoong Pharmaceutical, Hanmi Pharmaceutical, Lilly, Servier, Takeda, Bukwang Pharmaceutical, and Handok Pharmaceutical outside the submitted work. IG, ER, ML, EAON, PC, SS, KDK, SSE, and EL are employees of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, and may own stock and/or hold stock options in the Company. PUBLISHER'S NOTE: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. EDAT- 2017/11/08 06:00 MHDA- 2018/07/10 06:00 PMCR- 2017/11/06 CRDT- 2017/11/08 06:00 PHST- 2017/04/15 00:00 [received] PHST- 2017/10/13 00:00 [accepted] PHST- 2017/11/08 06:00 [entrez] PHST- 2017/11/08 06:00 [pubmed] PHST- 2018/07/10 06:00 [medline] PHST- 2017/11/06 00:00 [pmc-release] AID - 10.1186/s12902-017-0219-x [pii] AID - 219 [pii] AID - 10.1186/s12902-017-0219-x [doi] PST - epublish SO - BMC Endocr Disord. 2017 Nov 6;17(1):70. doi: 10.1186/s12902-017-0219-x.