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INTRODUCTION: Dipeptidyl peptidase 4 (DPP4) inhibitors are widely used in patients with type 2 diabetes mellitus (T2DM) on maintenance hemodialysis (HD), but the efficacy of the once-weekly DPP4 inhibitor omarigliptin is not known. METHODS: This prospective, randomized, open-label, parallel-group, non-inferiority/superiority, once-daily DPP4 inhibitor linagliptin-controlled, multicenter study examined glycemic control and safety of omarigliptin (UMIN000024284). Sample size was calculated to confirm non-inferiority in terms of changes in glycated hemoglobin (HbA1c). We enrolled 33 patients with T2DM on maintenance HD who had been treated with linagliptin for at least 3 months. The patients were randomized to receive omarigliptin (12.5 mg/week; n = 16) or linagliptin (5 mg/day; n = 17). Primary endpoints were changes in HbA1c and glycoalbumin (GA) over 24 weeks. RESULTS: Differences in the mean change in primary endpoint values between the omarigliptin and linagliptin groups were - 0.61% [- 1.14, - 0.09] for HbA1c, with a two-tailed upper 95% limit (i.e., one-tailed 97.5% upper limit) of 0.25%, below the non-inferiority limit, and - 1.67% [- 4.23, + 0.88] for GA, with a two-tailed upper 95% limit of 0.75%, above the non-inferiority limit. At 24 weeks, the omarigliptin group showed significantly greater reduction in HbA1c than the linagliptin group (- 0.2% ± 0.6% vs. 0.4% ± 0.8%, two-tailed p = 0.024) and significantly greater reduction in blood glucose after a single HD session (- 18.4 ± 31.4 mg/dL vs. 25.2 ± 59.5 mg/dL, respectively, two-tailed p = 0.019). No subjects in the omarigliptin group developed hypoglycemia. CONCLUSIONS: Our data showed that omarigliptin was non-inferior to linagliptin in glycemic control. Omarigliptin is feasible for glycemic control in patients with T2DM on maintenance HD. CLINICAL TRIALS REGISTRATION: UMIN000024284.
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OBJECTIVE: To find useful indices to identify subjects at high risk for developing diabetes. METHODS: We retrospectively reviewed 75-g oral glucose tolerance test (OGTT) surveys conducted during 1980 to 2001 in a Japanese community. Using personal charts of the surveys, 230 non-diabetics were followed for progression to type 2 diabetes. The usefulness of HbA(1C), fasting (Glucose(0)) and 1-hour (Glucose(60)) glucose levels during OGTT, and indices for insulin resistance and/or secretion to identify high risk subjects for diabetes were then analyzed. MATERIALS: Data described in personal charts of the OGTT program for residents of Nishikawa Town, Niigata Prefecture, Japan. RESULTS: During the 4.3+/-2.7 years of follow-up, 52 subjects progressed to type 2 diabetes. Assessing glucose and insulin levels during OGTT, Glucose(0), Glucose(60), "Insulin Response Ratio" (IRR(30), Insulin at 30 minutes / Fasting insulin; IRR(60), insulin at 60 minutes / fasting insulin), and insulin secretion / insulin resistance index (ISIRI(30)) were significantly associated with progression to type 2 diabetes even after the result for OGTT, body mass index, and familial history of diabetes were adjusted. These were also able to identify still higher risk subjects for type 2 diabetes from those with impaired glucose tolerance (IGT) although other indices for insulin resistance or secretion and hemoglobin A(1C) were less contributable for this purpose. CONCLUSION: A combination of Glucose(0) and Glucose(60) can most cost effectively identify high risk subjects for type 2 diabetes from IGT. IRR(30), IRR(60) and ISIRI(30) can also be used for such identification. However, further studies are needed to clarify whether these indices are superior to Glucose(0) and Glucose(60).
