uracil and Fasting Hypoglycemia studies

Fasting Hypoglycemia: HYPOGLYCEMIA expressed in the postabsorptive state, after prolonged FASTING, or an overnight fast.

Research Excerpts

Excerpt	Relevance	Reference
"Adding alogliptin to previous insulin therapy (with or without metformin) significantly improved glycaemic control in patients with type 2 diabetes inadequately controlled on insulin, without causing weight gain or increasing the incidence of hypoglycaemia."	9.14	Alogliptin added to insulin therapy in patients with type 2 diabetes reduces HbA(1C) without causing weight gain or increased hypoglycaemia. ( Fleck, PR; Gross, JL; Mekki, Q; Rendell, MS; Rosenstock, J; Wilson, CA, 2009)
"Once-weekly trelagliptin and once-daily alogliptin improved glycemic control and reduced GV without inducing hypoglycemia."	5.30	A Randomized Pilot Study of the Effect of Trelagliptin and Alogliptin on Glycemic Variability in Patients with Type 2 Diabetes. ( Koike, Y; Miyata, K; Nishimura, R; Osonoi, T; Shimasaki, Y, 2019)
"The EXAMINE trial randomized 5380 patients with type 2 diabetes (T2DM) and a recent acute coronary syndrome (ACS) event, in 49 countries, to double-blind treatment with alogliptin or placebo in addition to standard of care."	5.24	Relationship of glycated haemoglobin and reported hypoglycaemia to cardiovascular outcomes in patients with type 2 diabetes and recent acute coronary syndrome events: The EXAMINE trial. ( Bakris, GL; Bergenstal, RM; Cannon, CP; Cushman, WC; Gourlie, NM; Heller, SR; Kupfer, S; Liu, Y; Mehta, CR; Nissen, SE; White, WB; Wilson, CA; Zannad, F, 2017)
"Alogliptin monotherapy maintained glycaemic control comparable to that of glipizide in elderly patients with T2DM over 1 year of treatment, with substantially lower risk of hypoglycaemia and without weight gain."	5.17	Alogliptin versus glipizide monotherapy in elderly type 2 diabetes mellitus patients with mild hyperglycaemia: a prospective, double-blind, randomized, 1-year study. ( Fleck, P; Rosenstock, J; Wilson, C, 2013)
"Adding alogliptin to previous insulin therapy (with or without metformin) significantly improved glycaemic control in patients with type 2 diabetes inadequately controlled on insulin, without causing weight gain or increasing the incidence of hypoglycaemia."	5.14	Alogliptin added to insulin therapy in patients with type 2 diabetes reduces HbA(1C) without causing weight gain or increased hypoglycaemia. ( Fleck, PR; Gross, JL; Mekki, Q; Rendell, MS; Rosenstock, J; Wilson, CA, 2009)
"Dipeptidyl peptidase-4 (DPP-4) inhibitors such as alogliptin are becoming more widely established as treatment options for patients with type 2 diabetes (T2DM) because of their ability to improve glycemic control without increasing the risk of hypoglycemia or weight gain."	4.93	Alogliptin for the treatment of type 2 diabetes: a drug safety evaluation. ( Seino, Y; Yabe, D, 2016)
" The overall frequency of adverse events was similar among the groups."	2.84	Randomized, double-blind, phase III study to evaluate the efficacy and safety of once-daily treatment with alogliptin and metformin hydrochloride in Japanese patients with type 2 diabetes. ( Kaku, K; Katou, M; Kinugawa, Y; Nishiyama, Y; Sumino, S, 2017)
" The percentage of subjects who experienced all adverse events including hypoglycemia with alogliptin were comparable to those with placebo."	2.80	[Efficacy and safety of alogliptin in treatment of type 2 diabetes mellitus: a multicenter, randomized, double-blind, placebo-controlled phase III clinical trial in mainland China]. ( Bu, R; Gu, W; Han, P; Ji, Q; Jiang, Z; Lei, M; Li, C; Li, L; Li, W; Li, X; Li, Z; Liu, J; Liu, X; Liu, Y; Liu, Z; Lu, J; Lyu, X; Pan, C; Peng, Y; Qu, S; Shi, B; Song, Q; Xu, X; Xue, Y; Yan, L; Yang, J; Zeng, J; Zheng, B, 2015)
" Incidences of adverse effects were comparable between groups, with no relevant increases in hypoglycemia or weight gain seen."	2.79	Efficacy and safety of alogliptin added to insulin in Japanese patients with type 2 diabetes: a randomized, double-blind, 12-week, placebo-controlled trial followed by an open-label, long-term extension phase. ( Kaku, K; Kanoo, T; Katou, M; Mori, M; Seino, Y, 2014)
"Alogliptin is a dipeptidyl peptidase-4 inhibitor under investigation for treatment of patients with type 2 diabetes mellitus."	2.74	Coadministration of pioglitazone or glyburide and alogliptin: pharmacokinetic drug interaction assessment in healthy participants. ( Fleck, P; Karim, A; Laurent, A; Mekki, Q; Munsaka, M; Wann, E, 2009)
"Alogliptin is a highly selective dipeptidyl peptidase-4 (DPP-4) inhibitor that is under development for the treatment of type 2 diabetes."	2.73	Pharmacokinetics, pharmacodynamics, and tolerability of single increasing doses of the dipeptidyl peptidase-4 inhibitor alogliptin in healthy male subjects. ( Christopher, R; Covington, P; Davenport, M; Fleck, P; Karim, A; Mekki, QA; Wann, ER, 2008)

Research

Studies (19)

Authors

Clinical Trials (5)

Trial Overview

Trial Outcomes

Number of Participants Reporting One or More Treatment-emergent Adverse Events

Change From Baseline in AUC for Blood Glucose

Timeframe	Studies, this research(%)	All Research%
pre-1990	0 (0.00)	18.7374
1990's	0 (0.00)	18.2507
2000's	3 (15.79)	29.6817
2010's	16 (84.21)	24.3611
2020's	0 (0.00)	2.80

Authors	Studies
Nishimura, R	1
Osonoi, T	1
Koike, Y	1
Miyata, K	1
Shimasaki, Y	1
Lingvay, I	1
Takahara, M	1
Shiraiwa, T	1
Katakami, N	1
Maeno, Y	1
Yamamoto, K	1
Shiraiwa, Y	1
Yoshida, Y	1
Matsuoka, TA	1
Shimomura, I	1
Hu, J	1
Yang, C	1
Wang, H	1
Li, J	1
Tan, X	1
Wang, J	1
Zhang, B	1
Zhao, Y	1
Rosenstock, J	2
Wilson, C	3
Fleck, P	5
Charbonnel, B	1
Schweizer, A	1
Dejager, S	1
Pratley, RE	1
Del Prato, S	1
Camisasca, R	1
Kaku, K	2
Mori, M	1
Kanoo, T	1
Katou, M	2
Seino, Y	2
Yabe, D	1
Pan, C	1
Li, W	1
Zeng, J	1
Li, C	1
Yang, J	1
Ji, Q	1
Lu, J	1
Lyu, X	1
Li, X	2
Qu, S	1
Xu, X	1
Xue, Y	1
Li, L	2
Jiang, Z	1
Zheng, B	1
Bu, R	1
Han, P	1
Liu, Y	2
Liu, J	1
Peng, Y	1
Liu, X	1
Liu, Z	1
Yan, L	1
Lei, M	1
Song, Q	1
Shi, B	1
Gu, W	1
Li, Z	1
Sumino, S	1
Nishiyama, Y	1
Kinugawa, Y	1
Heller, SR	1
Bergenstal, RM	1
White, WB	1
Kupfer, S	1
Bakris, GL	1
Cushman, WC	1
Mehta, CR	1
Nissen, SE	1
Wilson, CA	2
Zannad, F	1
Gourlie, NM	1
Cannon, CP	1
Ji, L	1
Kuang, J	1
Yang, T	1
Kim, DJ	1
Kadir, AA	1
Huang, CN	1
Lee, D	1
Karim, A	2
Laurent, A	1
Munsaka, M	1
Wann, E	1
Mekki, Q	2
Rendell, MS	1
Gross, JL	1
Fleck, PR	1
Kutoh, E	1
Ukai, Y	1
Kusunoki, Y	1
Katsuno, T	1
Myojin, M	1
Miyakoshi, K	1
Ikawa, T	1
Matsuo, T	1
Ochi, F	1
Tokuda, M	1
Murai, K	1
Miuchi, M	1
Hamaguchi, T	1
Miyagawa, J	1
Namba, M	1
Christopher, R	1
Covington, P	1
Davenport, M	1
Mekki, QA	1
Wann, ER	1

Trial	Phase	Enrollment	Study Type	Start Date	Status
An Exploratory Study to Evaluate the Effects of Trelagliptin and Alogliptin by CGM on Glucose Variability for One Week in Patients With Type 2 Diabetes Mellitus[NCT02771093]	Phase 4	27 participants (Actual)	Interventional	2016-09-08	Completed
Effect of a Quadruple Therapy on Pancreatic Islet Function, Insulin Resistance and Cardiovascular Function in Patients With Mixed Prediabetes and Obesity: Randomized Clinical Trial[NCT04131582]	Phase 3	34 participants (Anticipated)	Interventional	2019-09-01	Recruiting
A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Determine the Efficacy and Safety of Alogliptin Plus Metformin, Alogliptin Alone, or Metformin Alone in Subjects With Type 2 Diabetes[NCT01023581]	Phase 3	784 participants (Actual)	Interventional	2009-11-30	Completed
A Phase 3 Study to Investigate the Efficacy and Safety of SYR-322 When Used in Combination With Insulin Preparation in Subjects With Type 2 Diabetes in Japan[NCT01521962]	Phase 3	67 participants (Actual)	Interventional	2012-02-29	Completed
A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Determine the Efficacy and Safety of SYR110322 (SYR-322) When Used in Combination With Insulin in Subjects With Type 2 Diabetes[NCT00286429]	Phase 3	390 participants (Actual)	Interventional	2006-02-28	Completed
[information is prepared from clinicaltrials.gov, extracted Sep-2024]

Intervention	Participants (Count of Participants)
Trelagliptin 100 mg	1
Alogliptin 25 mg	2

Change from baseline in AUC for blood glucose levels at each time points was calculated. (NCT02771093)
Timeframe: Baseline, up to 28 days

Change From Baseline in AUC for Blood Glucose During Periods When Blood Glucose Levels is Less Than 70 mg/dL (Hypoglycemia)

Intervention	mg·min/dL (Mean)
	D2W3	D3W3	D4W3	D5W3	D6W3	D7W3	D8W3
Alogliptin 25 mg	-4828.9	-3594.8	-4565.6	-5023.4	-4526.4	-4097.5	-4302.9
Trelagliptin 100 mg	-2340.4	-2348.4	-3723.2	-4017.8	-2408.2	-1837.6	-2438.5

Change from baseline in AUC for blood glucose during periods when blood glucose levels was less than 70 mg/dL at each time points was calculated. (NCT02771093)
Timeframe: Baseline, up to 28 days

Change From Baseline in AUC for Blood Glucose During Periods When Blood Glucose Levels Reached 110 mg/dL (Hypoglycemia)

Intervention	mg·min/dL (Mean)
	D2W3	D3W3	D4W3	D5W3	D6W3	D7W3	D8W3
Alogliptin 25 mg	0.4	0.0	13.4	26.9	0.0	0.0	0.0
Trelagliptin 100 mg	-31.2	-43.0	-42.3	-30.5	-39.8	-43.0	-43.0

Change from baseline in AUC for blood glucose during periods when blood glucose levels reached 110 mg/dL at each time points was calculated. (NCT02771093)
Timeframe: Baseline, up to 28 days

Change From Baseline in AUC for Blood Glucose During Periods When Blood Glucose Levels Reached 140 mg/dL (Hyperglycemia)

Intervention	mg·min/dL (Mean)
	D2W3	D3W3	D4W3	D5W3	D6W3	D7W3	D8W3
Alogliptin 25 mg	-4735.1	-3742.8	-4576.9	-4812.0	-4592.1	-4169.3	-4335.7
Trelagliptin 100 mg	-2263.8	-2479.2	-3755.3	-3845.6	-2581.9	-2184.1	-2634.2

Change from baseline in AUC for blood glucose during periods when blood glucose levels reached 140 mg/dL at each time points was calculated. (NCT02771093)
Timeframe: Baseline, up to 28 days

Change From Baseline in AUC for Blood Glucose During Periods When Blood Glucose Levels Reached 160 mg/dL (Hyperglycemia)

Intervention	mg·min/dL (Mean)
	D2W3	D3W3	D4W3	D5W3	D6W3	D7W3	D8W3
Alogliptin 25 mg	-4021.4	-3378.3	-4119.9	-4230.4	-3840.0	-3566.4	-3667.1
Trelagliptin 100 mg	-1935.9	-2001.2	-2978.2	-2981.5	-2550.5	-1946.5	-2043.5

Change from baseline in AUC for blood glucose during periods when blood glucose levels reached 160 mg/dL at each time points was calculated. (NCT02771093)
Timeframe: Baseline, up to 28 days

Change From Baseline in AUC for Blood Glucose During Periods When Blood Glucose Levels Reached 180 mg/dL (Hyperglycemia)

Intervention	mg·min/dL (Mean)
	D2W3	D3W3	D4W3	D5W3	D6W3	D7W3	D8W3
Alogliptin 25 mg	-3075.8	-2767.3	-3273.0	-3384.5	-2990.8	-2768.9	-2818.8
Trelagliptin 100 mg	-1458.0	-1702.0	-2335.8	-2171.8	-2031.0	-1636.5	-1603.9

Change from baseline in AUC for blood glucose during periods when blood glucose levels reached 180 mg/dL at each time points was calculated. (NCT02771093)
Timeframe: Baseline, up to 28 days

Change From Baseline in AUC for Blood Glucose When Specific Blood Glucose Levels (110 mg/dL) Are Observed During the 3 Hour Time Period After Breakfast, Lunch and Evening Meal

Intervention	mg·min/dL (Mean)
	D2W3	D3W3	D4W3	D5W3	D6W3	D7W3	D8W3
Alogliptin 25 mg	-2247.9	-2086.7	-2352.2	-2492.3	-2109.1	-1976.3	-2009.8
Trelagliptin 100 mg	-989.9	-1332.7	-1685.1	-1486.5	-1449.4	-1264.2	-1166.8

Change from baseline in AUC for blood glucose when specific blood glucose levels (110 mg/dL) were observed during the 3 hour time period after breakfast, lunch and evening meal at each time points was calculated. (NCT02771093)
Timeframe: Baseline, up to 28 days

Change From Baseline in AUC for Blood Glucose When Specific Blood Glucose Levels (140 mg/dL) Are Observed During the 3 Hour Time Period After Breakfast, Lunch and Evening Meal

Intervention	mg·min/dL (Mean)
	D2W3 after breakfast	D3W3 after breakfast	D4W3 after breakfast	D5W3 after breakfast	D6W3 after breakfast	D7W3 after breakfast	D8W3 after breakfast	D2W3 after lunch	D3W3 after lunch	D4W3 after lunch	D5W3 after lunch	D6W3 after lunch	D7W3 after lunch	D8W3 after lunch	D2W3 after evening meal	D3W3 after evening meal	D4W3 after evening meal	D5W3 after evening meal	D6W3 after evening meal	D7W3 after evening meal	D8W3 after evening meal
Alogliptin 25 mg	-1052.7	-1030.9	-958.9	-1319.8	-832.5	-966.3	-1024.8	-1131.4	-941.9	-701.1	-1065.4	-534.4	-488.7	-923.5	-800.5	-1023.6	-1228.5	-756.1	-1144.2	-669.9	-577.0
Trelagliptin 100 mg	-203.7	-662.6	-1024.6	-97.2	-696.1	-573.8	-399.0	-669.0	-500.1	-468.2	-793.5	-798.5	-320.4	-521.3	-1079.4	-1273.0	-1359.6	-1351.4	-1199.9	-884.2	-1142.0

Change from baseline in AUC for blood glucose when specific blood glucose levels (140 mg/dL) were observed during the 3 hour time period after breakfast, lunch and evening meal at each time points was calculated. (NCT02771093)
Timeframe: Baseline, up to 28 days

Change From Baseline in AUC for Blood Glucose When Specific Blood Glucose Levels (160 mg/dL) Are Observed During the 3 Hour Time Period After Breakfast, Lunch and Evening Meal

Intervention	mg·min/dL (Mean)
	D2W3 after breakfast	D3W3 after breakfast	D4W3 after breakfast	D5W3 after breakfast	D6W3 after breakfast	D7W3 after breakfast	D8W3 after breakfast	D2W3 after lunch	D3W3 after lunch	D4W3 after lunch	D5W3 after lunch	D6W3 after lunch	D7W3 after lunch	D8W3 after lunch	D2W3 after evening meal	D3W3 after evening meal	D4W3 after evening meal	D5W3 after evening meal	D6W3 after evening meal	D7W3 after evening meal	D8W3 after evening meal
Alogliptin 25 mg	-981.2	-926.1	-801.6	-1178.0	-791.8	-910.1	-951.6	-1079.1	-845.4	-648.1	-970.0	-517.0	-458.3	-867.4	-637.6	-862.0	-1016.8	-613.7	-966.4	-586.4	-535.0
Trelagliptin 100 mg	-218.5	-510.2	-886.4	-21.3	-559.8	-457.4	-348.5	-588.5	-489.7	-429.3	-725.5	-707.9	-294.9	-474.7	-950.8	-1077.3	-1147.1	-1147.5	-1030.6	-822.3	-964.8

Change from baseline in AUC for blood glucose when specific blood glucose levels (160 mg/dL) were observed during the 3 hour time period after breakfast, lunch and evening meal at each time points was calculated. (NCT02771093)
Timeframe: Baseline, up to 28 days

Change From Baseline in AUC for Blood Glucose When Specific Blood Glucose Levels (180 mg/dL) Are Observed During the 3 Hour Time Period After Breakfast, Lunch and Evening Meal

Intervention	mg·min/dL (Mean)
	D2W3 after breakfast	D3W3 after breakfast	D4W3 after breakfast	D5W3 after breakfast	D6W3 after breakfast	D7W3 after breakfast	D8W3 after breakfast	D2W3 after lunch	D3W3 after lunch	D4W3 after lunch	D5W3 after lunch	D6W3 after lunch	D7W3 after lunch	D8W3 after lunch	D2W3 after evening meal	D3W3 after evening meal	D4W3 after evening meal	D5W3 after evening meal	D6W3 after evening meal	D7W3 after evening meal	D8W3 after evening meal
Alogliptin 25 mg	-829.2	-770.4	-609.9	-981.3	-696.8	-760.4	-806.3	-890.4	-705.5	-552.5	-811.9	-469.7	-384.6	-730.1	-507.4	-671.1	-808.9	-508.3	-759.6	-504.1	-460.2
Trelagliptin 100 mg	-164.5	-377.8	-759.4	25.6	-405.5	-356.6	-273.4	-448.1	-462.2	-389.7	-579.4	-534.1	-249.9	-350.8	-730.5	-825.2	-914.5	-887.5	-809.5	-742.3	-763.4

Change from baseline in AUC for blood glucose when specific blood glucose levels (180 mg/dL) were observed during the 3 hour time period after breakfast, lunch and evening meal at each time points was calculated. (NCT02771093)
Timeframe: Baseline, up to 28 days

Change From Baseline in Maximum Variation of Blood Glucose Levels Between Before and After Breakfast, Lunch, and Evening Meal

Intervention	mg·min/dL (Mean)
	D2W3 after breakfast	D3W3 after breakfast	D4W3 after breakfast	D5W3 after breakfast	D6W3 after breakfast	D7W3 after breakfast	D8W3 after breakfast	D2W3 after lunch	D3W3 after lunch	D4W3 after lunch	D5W3 after lunch	D6W3 after lunch	D7W3 after lunch	D8W3 after lunch	D2W3 after evening meal	D3W3 after evening meal	D4W3 after evening meal	D5W3 after evening meal	D6W3 after evening meal	D7W3 after evening meal	D8W3 after evening meal
Alogliptin 25 mg	-660.1	-592.9	-375.6	-776.3	-556.5	-578.2	-603.6	-626.6	-521.1	-404.1	-589.9	-354.6	-293.6	-546.4	-375.9	-484.4	-597.2	-427.8	-552.4	-374.5	-346.5
Trelagliptin 100 mg	-90.7	-241.2	-632.2	36.5	-272.2	-264.2	-214.8	-300.3	-383.8	-307.0	-430.4	-353.5	-184.2	-234.0	-507.6	-592.4	-662.4	-641.9	-598.8	-612.6	-555.4

Change from baseline in maximum variation of glucose levels between before and after breakfast, lunch and evening meal at each time points was calculated. (NCT02771093)
Timeframe: Baseline, up to 28 days

Change From Baseline in Mean 24-hour Blood Glucose Levels

Intervention	mg/dL (Mean)
	D2W3 between before/after breakfast	D3W3 between before/after breakfast	D4W3 between before/after breakfast	D5W3 between before/after breakfast	D6W3 between before/after breakfast	D7W3 between before/after breakfast	D8W3 between before/after breakfast	D2W3 between before/after lunch	D3W3 between before/after lunch	D4W3 between before/after lunch	D5W3 between before/after lunch	D6W3 between before/after lunch	D7W3 between before/after lunch	D8W3 between before/after lunch	D2W3 between before/after evening meal	D3W3 between before/after evening meal	D4W3 between before/after evening meal	D5W3 between before/after evening meal	D6W3 between before/after evening meal	D7W3 between before/after evening meal	D8W3 between before/after evening meal
Alogliptin 25 mg	-28.9	-35.4	-42.1	-25.5	-29.8	-33.3	-34.5	-35.5	-29.5	-6.2	-31.2	-13.1	-14.9	-29.1	-15.6	-21.8	-24.2	-5.2	-24.6	-4.4	-6.6
Trelagliptin 100 mg	-13.9	-47.4	-41.2	-7.0	-38.6	-36.4	-36.2	-30.2	-34.5	-23.8	-34.8	-37.0	-12.7	-15.6	-37.8	-49.1	-42.6	-31.5	-41.9	-33.6	-39.3

Change from baseline in mean 24-hour blood glucose levels at each time points was calculated. (NCT02771093)
Timeframe: Baseline, up to 28 days

Change From Baseline in Mean Amplitude Glycemic Excursions (MAGE)

Intervention	mg/dL (Mean)
	D2W3	D3W3	D4W3	D5W3	D6W3	D7W3	D8W3
Alogliptin 25 mg	-16.77	-12.46	-15.85	-17.46	-15.79	-14.23	-14.94
Trelagliptin 100 mg	-8.14	-8.15	-13.12	-13.95	-8.37	-6.38	-8.46

Change from baseline in MAGE at each time points was calculated. (NCT02771093)
Timeframe: Baseline, up to 28 days

Change From Baseline in Mean Daytime Blood Glucose Levels

Intervention	mg/dL (Mean)
	D2W3	D3W3	D4W3	D5W3	D6W3	D7W3	D8W3
Alogliptin 25 mg	-47.25	-52.75	-44.67	-50.22	-34.82	-37.18	-41.38
Trelagliptin 100 mg	-28.42	-33.72	-36.08	-23.12	-38.05	-25.74	-24.26

Change from baseline in mean daytime blood glucose levels at each time points was calculated. (NCT02771093)
Timeframe: Baseline, up to 28 days

Change From Baseline in Mean Nocturnal Blood Glucose Levels

Intervention	mg/dL (Mean)
	D2W3	D3W3	D4W3	D5W3	D6W3	D7W3	D8W3
Alogliptin 25 mg	-20.38	-17.21	-21.80	-22.54	-19.34	-16.92	-19.78
Trelagliptin 100 mg	-11.08	-12.48	-18.42	-19.53	-14.27	-10.86	-12.90

Change from baseline in mean nocturnal blood glucose levels at each time points was calculated. (NCT02771093)
Timeframe: Baseline, up to 28 days

Change From Baseline in Peak Postprandial Glucose Levels During the 3 Hour Time Period After Breakfast, Lunch and Evening Meal

Intervention	mg/dL (Mean)
	D2W3	D3W3	D4W3	D5W3	D6W3	D7W3	D8W3
Alogliptin 25 mg	-10.69	-3.38	-3.76	-6.43	-7.98	-8.59	-5.96
Trelagliptin 100 mg	-2.65	0.52	-3.17	-4.09	5.55	3.86	1.06

Change from baseline in peak postprandial glucose levels during the 3 hour time period after breakfast, lunch and evening meal at each time points was calculated. (NCT02771093)
Timeframe: Baseline, up to 28 days

Change From Baseline in Time During Periods When Blood Glucose Levels Reached 140 mg/dL (Hyperglycemia)

Intervention	mg/dL (Mean)
	D2W3 after breakfast	D3W3 after breakfast	D4W3 after breakfast	D5W3 after breakfast	D6W3 after breakfast	D7W3 after breakfast	D8W3 after breakfast	D2W3 after lunch	D3W3 after lunch	D4W3 after lunch	D5W3 after lunch	D6W3 after lunch	D7W3 after lunch	D8W3 after lunch	D2W3 after evening meal	D3W3 after evening meal	D4W3 after evening meal	D5W3 after evening meal	D6W3 after evening meal	D7W3 after evening meal	D8W3 after evening meal
Alogliptin 25 mg	-35.6	-29.1	-29.0	-41.1	-24.2	-29.6	-31.4	-40.8	-35.1	-16.6	-41.6	-18.7	-18.1	-33.6	-21.3	-21.6	-32.7	-15.6	-33.8	-13.9	-15.9
Trelagliptin 100 mg	-11.3	-35.4	-39.4	-4.9	-28.6	-23.7	-16.6	-26.9	-25.9	-21.9	-34.8	-32.7	-11.5	-17.7	-40.6	-44.5	-45.8	-40.6	-41.5	-32.3	-42.2

Change from baseline in cumulative time during periods when blood glucose levels reached 140 mg/dL at each time points was calculated. (NCT02771093)
Timeframe: Baseline, up to 28 days

Change From Baseline in Time During Periods When Blood Glucose Levels Reached 160 mg/dL (Hyperglycemia)

Intervention	min (Mean)
	D2W3	D3W3	D4W3	D5W3	D6W3	D7W3	D8W3
Alogliptin 25 mg	-212.5	-147.1	-166.1	-163.2	-193.2	-182.1	-198.6
Trelagliptin 100 mg	-116.9	-105.0	-163.8	-192.3	-114.2	-96.9	-133.8

Change from baseline in cumulative time during periods when blood glucose levels reached 160 mg/dL at each time points was calculated. (NCT02771093)
Timeframe: Baseline, up to 28 days

Change From Baseline in Time During Periods When Blood Glucose Levels Reached 180 mg/dL (Hyperglycemia)

Intervention	min (Mean)
	D2W3	D3W3	D4W3	D5W3	D6W3	D7W3	D8W3
Alogliptin 25 mg	-229.3	-173.2	-234.3	-236.8	-232.9	-213.2	-225.4
Trelagliptin 100 mg	-134.2	-75.0	-167.7	-200.0	-153.1	-93.5	-115.0

Change from baseline in cumulative time during periods when blood glucose levels reached 180 mg/dL at each time points was calculated. (NCT02771093)
Timeframe: Baseline, up to 28 days

Changes From Baseline in the SD of Daytime Blood Glucose Values

Intervention	min (Mean)
	D2W3	D3W3	D4W3	D5W3	D6W3	D7W3	D8W3
Alogliptin 25 mg	-210.7	-167.1	-236.4	-225.4	-216.8	-194.3	-193.2
Trelagliptin 100 mg	-91.2	-117.3	-167.3	-153.1	-137.7	-94.2	-105.0

Change from baseline in SD of daytime blood glucose values at each time points was calculated. (NCT02771093)
Timeframe: Baseline, up to 28 days

Changes From Baseline in the SD of Nocturnal Blood Glucose Values

Intervention	mg/dL (Mean)
	D2W3	D3W3	D4W3	D5W3	D6W3	D7W3	D8W3
Alogliptin 25 mg	-13.28	-13.12	-10.98	-12.54	-10.44	-9.49	-10.81
Trelagliptin 100 mg	-9.78	-12.82	-11.98	-10.88	-11.94	-8.13	-6.49

Change from baseline in SD of nocturnal blood glucose values at each time points was calculated. (NCT02771093)
Timeframe: Baseline, up to 28 days

Changes From Baseline in the Standard Deviation (SD) of 24-hour Blood Glucose Values

Intervention	mg/dL (Mean)
	D2W3	D3W3	D4W3	D5W3	D6W3	D7W3	D8W3
Alogliptin 25 mg	-2.45	-9.76	-7.86	-5.21	-8.23	-8.01	-6.64
Trelagliptin 100 mg	-0.71	-3.55	-4.06	-2.96	-5.67	-5.25	-2.93

Changes in the SD of 24-hour blood glucose values (mg/dL) for each 7-day period between Week 3 and Week 4 (between Day 2 on Week 3 [Day 22] and Day 8 on Week 3 [Day 28]) of the treatment period, calculated from the value at the start of the observation period. (NCT02771093)
Timeframe: Baseline, up to 28 days

Standard Deviation (SD) of 24-hour Blood Glucose Values

Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 26

Intervention	mg/dL (Mean)
	Day(D) 2 Week(W) 3	D3W3	D4W3	D5W3	D6W3	D7W3	D8W3
Alogliptin 25 mg	-13.04	-15.24	-12.91	-13.28	-11.94	-10.90	-11.63
Trelagliptin 100 mg	-7.51	-11.76	-11.71	-9.89	-12.75	-9.50	-7.35

Intervention	mg/dL (Mean)
	Baseline	D2W3	D3W3	D4W3	D5W3	D6W3	D7W3	D8W3
Alogliptin 25 mg	40.44	27.41	25.20	27.54	27.16	28.51	29.54	28.81
Trelagliptin 100 mg	38.18	30.68	26.42	26.48	28.29	25.44	28.68	30.84

The change from Baseline to Week 26 in HbA1c (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound). (NCT01023581)
Timeframe: Baseline and Week 26.

Change From Baseline in Fasting Plasma Glucose Over Time

Intervention	percentage glycosylated hemoglobin (Least Squares Mean)
Placebo	0.15
Alogliptin 25 QD	-0.52
Alogliptin 12.5 BID	-0.56
Metformin 500 BID	-0.65
Metformin 1000 BID	-1.11
Alogliptin 12.5 BID + Metformin 500 BID	-1.22
Alogliptin 12.5 BID + Metformin 1000 BID	-1.55

The change from Baseline in fasting plasma glucose was assessed at Weeks 1, 2, 4, 8, 12, 16, 20 and 26. Least Squares Means were from an ANCOVA model with treatment and geographic region as fixed effects, and baseline fasting plasma glucose as a covariate. (NCT01023581)
Timeframe: Baseline and Weeks 1, 2, 4, 8, 12, 16, 20 and 26.

Change From Baseline in HbA1c Over Time

Intervention	mg/dL (Least Squares Mean)
	Week 1 (n=102, 103, 94, 95, 104, 101, 109)	Week 2 (n=105, 112, 105, 102, 108, 106, 111)	Week 4 (n=105, 112, 106, 106, 110, 106, 111)	Week 8 (n=105, 112, 106, 106, 110, 106, 112)	Week 12 (n=105, 112, 106, 106, 110, 106, 112)	Week 16 (n=105, 112, 106, 106, 110, 106, 112)	Week 20 (n=105, 112, 106, 106, 110, 106, 112)	Week 26 (n=105, 112, 106, 106, 110, 106, 112)
Alogliptin 12.5 BID	-11.9	-11.6	-16.6	-12.1	-14.7	-14.7	-12.3	-9.7
Alogliptin 12.5 BID + Metformin 1000 BID	-36.3	-43.6	-44.1	-43.8	-44.7	-47.7	-44.6	-45.9
Alogliptin 12.5 BID + Metformin 500 BID	-32.7	-34.5	-37.6	-32.9	-31.6	-35.9	-33.8	-31.7
Alogliptin 25 QD	-3.9	-7.4	-11.5	-10.9	-9.7	-7.1	-9.2	-6.1
Metformin 1000 BID	-23.1	-22.2	-29.0	-30.7	-30.7	-33.5	-35.1	-31.9
Metformin 500 BID	-12.6	-14.5	-16.9	-11.8	-14.0	-13.3	-10.9	-11.5
Placebo	5.7	4.6	7.2	7.1	11.6	10.1	8.7	12.4

"The change from Baseline in HbA1c (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) was assessed at Weeks 4, 8, 12, 16 and 20.~Least squares means are from an analysis of covariance (ANCOVA) model with treatment and geographic region as fixed effects, and baseline HbA1c as a covariate." (NCT01023581)
Timeframe: Baseline and Weeks 4, 8, 12, 16, and 20.

Change From Baseline in Body Weight (Week 12).

Intervention	percentage glycosylated hemoglobin (Least Squares Mean)
	Week 4 (n=95, 97, 89, 94, 102, 94, 101)	Week 8 (n=102, 104, 104, 103, 108, 102, 111)	Week 12 (n=102, 104, 104, 103, 108, 102, 111)	Week 16 (n=102, 104, 104, 103, 108, 102, 111)	Week 20 (n=102, 104, 104, 103, 108, 102, 111)
Alogliptin 12.5 BID	-0.42	-0.58	-0.62	-0.63	-0.59
Alogliptin 12.5 BID + Metformin 1000 BID	-0.75	-1.17	-1.40	-1.50	-1.54
Alogliptin 12.5 BID + Metformin 500 BID	-0.70	-1.08	-1.22	-1.26	-1.25
Alogliptin 25 QD	-0.34	-0.51	-0.53	-0.58	-0.57
Metformin 1000 BID	-0.58	-0.86	-1.02	-1.09	-1.14
Metformin 500 BID	-0.37	-0.59	-0.68	-0.72	-0.68
Placebo	0.09	0.08	0.12	0.13	0.12

The change between Body Weight measured at week 12 and Body Weight measured at baseline. (NCT00286429)
Timeframe: Baseline and Week 12.

Change From Baseline in Body Weight (Week 20).

Intervention	kg (Least Squares Mean)
Placebo	0.50
Alogliptin 12.5 mg QD	0.44
Alogliptin 25 mg QD	0.31

The change between Body Weight measured at week 20 and Body Weight measured at baseline. (NCT00286429)
Timeframe: Baseline and Week 20.

Change From Baseline in Body Weight (Week 26).

Intervention	kg (Least Squares Mean)
Placebo	0.73
Alogliptin 12.5 mg QD	0.55
Alogliptin 25 mg QD	0.45

The change between Body Weight measured at week 26 or final visit and Body Weight measured at baseline. (NCT00286429)
Timeframe: Baseline and Week 26.

Change From Baseline in Body Weight (Week 8).

Intervention	kg (Least Squares Mean)
Placebo	0.63
Alogliptin 12.5 mg QD	0.68
Alogliptin 25 mg QD	0.60

The change between Body Weight measured at week 8 and Body Weight measured at baseline. (NCT00286429)
Timeframe: Baseline and Week 8.

Change From Baseline in C-peptide (Week 12).

Intervention	kg (Least Squares Mean)
Placebo	0.39
Alogliptin 12.5 mg QD	0.10
Alogliptin 25 mg QD	0.18

The change between the value of C-peptide collected at week 12 and C-peptide collected at baseline. (NCT00286429)
Timeframe: Baseline and Week 12.

Change From Baseline in C-peptide (Week 16).

Intervention	ng/mL (Least Squares Mean)
Placebo	0.207
Alogliptin 12.5 mg QD	0.333
Alogliptin 25 mg QD	0.390

The change between the value of C-peptide collected at week 16 and C-peptide collected at baseline. (NCT00286429)
Timeframe: Baseline and Week 16.

Change From Baseline in C-peptide (Week 20).

Intervention	ng/mL (Least Squares Mean)
Placebo	0.241
Alogliptin 12.5 mg QD	0.319
Alogliptin 25 mg QD	0.396

The change between the value of C-peptide collected at week 20 and C-peptide collected at baseline. (NCT00286429)
Timeframe: Baseline and Week 20.

Change From Baseline in C-peptide (Week 26).

Intervention	ng/mL (Least Squares Mean)
Placebo	0.239
Alogliptin 12.5 mg QD	0.318
Alogliptin 25 mg QD	0.281

The change between the value of C-peptide collected at week 26 or final visit and C-peptide collected at baseline. (NCT00286429)
Timeframe: Baseline and Week 26.

Change From Baseline in C-peptide (Week 4).

Intervention	ng/mL (Least Squares Mean)
Placebo	-0.083
Alogliptin 12.5 mg QD	0.199
Alogliptin 25 mg QD	0.042

The change between the value of C-peptide collected at week 4 and C-peptide collected at baseline. (NCT00286429)
Timeframe: Baseline and Week 4.

Change From Baseline in C-peptide (Week 8).

Intervention	ng/mL (Least Squares Mean)
Placebo	-0.023
Alogliptin 12.5 mg QD	0.132
Alogliptin 25 mg QD	0.453

The change between the value of C-peptide collected at week 8 and C-peptide collected at baseline. (NCT00286429)
Timeframe: Baseline and Week 8.

Change From Baseline in Fasting Plasma Glucose (Week 1).

Intervention	ng/mL (Least Squares Mean)
Placebo	-0.024
Alogliptin 12.5 mg QD	0.178
Alogliptin 25 mg QD	0.348

The change between the value of fasting plasma glucose collected at final visit or week 1 and fasting plasma glucose collected at baseline. (NCT00286429)
Timeframe: Baseline and Week 1.

Change From Baseline in Fasting Plasma Glucose (Week 12).

Intervention	mg/dL (Least Squares Mean)
Placebo	6.3
Alogliptin 12.5 mg QD	-5.0
Alogliptin 25 mg QD	-9.9

The change between the value of fasting plasma glucose collected at week 12 and fasting plasma glucose collected at baseline. (NCT00286429)
Timeframe: Baseline and Week 12.

Change From Baseline in Fasting Plasma Glucose (Week 16).

Intervention	mg/dL (Least Squares Mean)
Placebo	-1.4
Alogliptin 12.5 mg QD	-5.2
Alogliptin 25 mg QD	-2.9

The change between the value of fasting plasma glucose collected at week 16 and fasting plasma glucose collected at baseline. (NCT00286429)
Timeframe: Baseline and Week 16.

Change From Baseline in Fasting Plasma Glucose (Week 2).

Intervention	mg/dL (Least Squares Mean)
Placebo	4.6
Alogliptin 12.5 mg QD	-5.3
Alogliptin 25 mg QD	-6.3

The change between the value of fasting plasma glucose collected at week 2 and fasting plasma glucose collected at baseline. (NCT00286429)
Timeframe: Baseline and Week 2.

Change From Baseline in Fasting Plasma Glucose (Week 20).

Intervention	mg/dL (Least Squares Mean)
Placebo	1.0
Alogliptin 12.5 mg QD	-3.1
Alogliptin 25 mg QD	-11.4

The change between the value of fasting plasma glucose collected at week 20 and fasting plasma glucose collected at baseline. (NCT00286429)
Timeframe: Baseline and Week 20.

Change From Baseline in Fasting Plasma Glucose (Week 26).

Intervention	mg/dL (Least Squares Mean)
Placebo	8.6
Alogliptin 12.5 mg QD	-4.2
Alogliptin 25 mg QD	-11.3

The change between the value of fasting plasma glucose collected at week 26 or final visit and fasting plasma glucose collected at baseline. (NCT00286429)
Timeframe: Baseline and Week 26.

Change From Baseline in Fasting Plasma Glucose (Week 4).

Intervention	mg/dL (Least Squares Mean)
Placebo	5.8
Alogliptin 12.5 mg QD	2.3
Alogliptin 25 mg QD	-11.7

The change between the value of fasting plasma glucose collected at week 4 and fasting plasma glucose collected at baseline. (NCT00286429)
Timeframe: Baseline and Week 4.

Change From Baseline in Fasting Plasma Glucose (Week 8).

Intervention	mg/dL (Least Squares Mean)
Placebo	5.3
Alogliptin 12.5 mg QD	-5.0
Alogliptin 25 mg QD	-12.1

The change between the value of fasting plasma glucose collected at week 8 and fasting plasma glucose collected at baseline. (NCT00286429)
Timeframe: Baseline and Week 8.

Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 26.

Intervention	mg/dL (Least Squares Mean)
Placebo	5.4
Alogliptin 12.5 mg QD	-13.5
Alogliptin 25 mg QD	-14.1

The change in the value of glycosylated hemoglobin (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) collected at week 26 or final visit and glycosylated hemoglobin collected at baseline. (NCT00286429)
Timeframe: Baseline and Week 26.

Change From Baseline in Glycosylated Hemoglobin (Week 12).

Intervention	percentage of Glycosylated Hemoglobin (Least Squares Mean)
Placebo	-0.13
Alogliptin 12.5 mg QD	-0.63
Alogliptin 25 mg QD	-0.71

The change in the value of Glycosylated Hemoglobin (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) collected at week 12 and Glycosylated Hemoglobin collected at baseline. (NCT00286429)
Timeframe: Baseline and Week 12.

Change From Baseline in Glycosylated Hemoglobin (Week 16).

The change in the value of Glycosylated Hemoglobin (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) collected at week 16 and Glycosylated Hemoglobin collected at baseline. (NCT00286429)
Timeframe: Baseline and Week 16.

Change From Baseline in Glycosylated Hemoglobin (Week 20).

The change in the value of Glycosylated Hemoglobin (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) collected at week 20 and Glycosylated Hemoglobin collected at baseline. (NCT00286429)
Timeframe: Baseline and Week 20.

Change From Baseline in Glycosylated Hemoglobin (Week 4).

The change in the value of Glycosylated Hemoglobin (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) collected at week 4 and Glycosylated Hemoglobin collected at baseline. (NCT00286429)
Timeframe: Baseline and Week 4.

Change From Baseline in Glycosylated Hemoglobin (Week 8).

The change in the value of Glycosylated Hemoglobin (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) collected at week 8 and Glycosylated Hemoglobin collected at baseline. (NCT00286429)
Timeframe: Baseline and Week 8.

Number of Participants Requiring Rescue.

The number of participants requiring rescue for failing to achieve pre-specified glycemic targets during the 26 week study. (NCT00286429)
Timeframe: 26 Weeks.

Number of Participants With Glycosylated Hemoglobin ≤ 6.5%.

The number of participants with a value for the percentage of glycosylated hemoglobin (the percentage of hemoglobin that is bound to glucose) less than or equal to 6.5% during the 26 week study. (NCT00286429)
Timeframe: Baseline and Week 26.

Number of Participants With Glycosylated Hemoglobin ≤ 7.0%.

The number of participants with a value for the percentage of glycosylated hemoglobin (the percentage of hemoglobin that is bound to glucose) less than or equal to 7.0% during the 26 week study. (NCT00286429)
Timeframe: Baseline and Week 26.

Number of Participants With Glycosylated Hemoglobin ≤ 7.5%.

The number of participants with a value for the percentage of glycosylated hemoglobin (the percentage of hemoglobin that is bound to glucose) less than or equal to 7.5% during the 26 week study. (NCT00286429)
Timeframe: Baseline and Week 26.

Number of Participants With Glycosylated Hemoglobin Decrease From Baseline ≥ 0.5%.

The number of participants with a decrease from baseline in the percentage of glycosylated hemoglobin (the percentage of hemoglobin that is bound to glucose) greater than or equal to 0.5% during the 26 week study. (NCT00286429)
Timeframe: Baseline and Week 26.

Number of Participants With Glycosylated Hemoglobin Decrease From Baseline ≥ 1.0%.

The number of participants with a decrease from baseline in the percentage of glycosylated hemoglobin (the percentage of hemoglobin that is bound to glucose) greater than or equal to 1.0% during the 26 week study. (NCT00286429)
Timeframe: Baseline and Week 26.

Number of Participants With Glycosylated Hemoglobin Decrease From Baseline ≥ 1.5%.

The number of participants with a decrease from baseline in the percentage of glycosylated hemoglobin (the percentage of hemoglobin that is bound to glucose) greater than or equal to 1.5% during the 26 week study. (NCT00286429)
Timeframe: Baseline and Week 26.

Number of Participants With Glycosylated Hemoglobin Decrease From Baseline ≥ 2.0%.

The number of participants with a decrease from baseline in the percentage of glycosylated hemoglobin (the percentage of hemoglobin that is bound to glucose) greater than or equal to 2.0% during the 26 week study. (NCT00286429)
Timeframe: Baseline and Week 26.

Number of Participants With Marked Hyperglycemia (Fasting Plasma Glucose ≥ 200 mg Per dL).

The number of participants with a fasting plasma glucose value greater than or equal to 200 mg per dL during the 26 week study. (NCT00286429)
Timeframe: 26 Weeks.

Intervention	percentage of Glycosylated Hemoglobin (Least Squares Mean)
Placebo	-0.27
Alogliptin 12.5 mg QD	-0.84
Alogliptin 25 mg QD	-0.81

Intervention	percentage of Glycosylated Hemoglobin (Least Squares Mean)
Placebo	-0.22
Alogliptin 12.5 mg QD	-0.80
Alogliptin 25 mg QD	-0.76

Intervention	percentage of Glycosylated Hemoglobin (Least Squares Mean)
Placebo	-0.17
Alogliptin 12.5 mg QD	-0.76
Alogliptin 25 mg QD	-0.74

Intervention	percentage of Glycosylated Hemoglobin (Least Squares Mean)
Placebo	-0.26
Alogliptin 12.5 mg QD	-0.47
Alogliptin 25 mg QD	-0.58

Article	Year
SODIUM GLUCOSE COTRANSPORTER 2 AND DIPEPTIDYL PEPTIDASE-4 INHIBITION: PROMISE OF A DYNAMIC DUO. Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists, 2017, Volume: 23, Issue:7 Topics: Adamantane; Benzhydryl Compounds; Blood Glucose; Canagliflozin; Diabetes Mellitus, Type 2; Dipeptide	2017
An up-to-date evaluation of alogliptin benzoate for the treatment of type 2 diabetes. Expert opinion on pharmacotherapy, 2019, Volume: 20, Issue:14 Topics: Benzoates; Clinical Trials as Topic; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors;	2019
Combination therapy with DPP-4 inhibitors and insulin in patients with type 2 diabetes mellitus: what is the evidence? Hospital practice (1995), 2013, Volume: 41, Issue:2 Topics: Adamantane; Body Weight; Diabetes Complications; Diabetes Mellitus, Type 2; Dipeptides; Dipeptidyl-P	2013
Alogliptin for the treatment of type 2 diabetes: a drug safety evaluation. Expert opinion on drug safety, 2016, Volume: 15, Issue:2 Topics: Aged; Animals; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Humans; Hypoglycemia;	2016

uracil and Fasting Hypoglycemia