Safety and Efficacy of Omarigliptin (MK-3102), a Novel Once-Weekly DPP-4 Inhibitor for the Treatment of Patients With Type 2 Diabetes

Wayne H.-H. Sheu; Ira Gantz; Menghui Chen; Shailaja Suryawanshi; Arpana Mirza; Barry J. Goldstein; Keith D. Kaufman; Samuel S. Engel

doi:10.2337/dc15-0109

Safety and Efficacy of Omarigliptin (MK-3102), a Novel Once-Weekly DPP-4 Inhibitor for the Treatment of Patients With Type 2 Diabetes

Wayne H.-H. Sheu¹,
Ira Gantz² ⇑,
Menghui Chen²,
Shailaja Suryawanshi²,
Arpana Mirza²,
Barry J. Goldstein²,
Keith D. Kaufman² and
Samuel S. Engel²

¹Division of Endocrinology and Metabolism, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan; School of Medicine, National Yang-Ming University, Taipei, Taiwan; and College of Medicine, National Defense Medical Center, Taipei, Taiwan
²Merck & Co., Inc., Kenilworth, NJ

Corresponding author: Ira Gantz, ira.gantz{at}merck.com.

Diabetes Care 2015 Nov; 38(11): 2106-2114. https://doi.org/10.2337/dc15-0109

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Figure 1
Efficacy measures: HbA_1c through week 12 (A); PMG change from baseline at week 12 (B); FPG through week 12 (C); HbA_1c through week 78 (D). A and C: Gray circle, placebo; orange circle, omarigliptin 0.25 mg; green triangle, omarigliptin 1 mg; open triangle, omarigliptin 3 mg; orange square, omarigliptin 10 mg; blue square, omarigliptin 25 mg. D: Gray circle, placebo/metformin; orange circle, omarigliptin 0.25/25 mg; green triangle, omarigliptin 1/25 mg; open triangle, omarigliptin 3/25 mg; orange square, omarigliptin 10/25 mg; blue square, omarigliptin 25/25 mg. The LS estimates in A, B, and C are based on a model with terms for treatment, prior AHA therapy status (yes/no), geographic region (Japan/not Japan), and the interaction of time by treatment and time by prior AHA therapy status, with a constraint that the mean baseline is the same for all treatment groups. Note that the LS estimates in D are obtained from a model with the same terms without the constraint on the mean baseline because this analysis is based on a self-selected subset of randomized patients who entered the extension study.

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Table 1

Baseline demographic and anthropomorphic characteristics of base study treatment groups

Parameter	Placebo(n = 114)	Omarigliptin once weekly
Parameter	Placebo(n = 114)	0.25 mg(n = 113)	1 mg(n = 115)	3 mg(n = 114)	10 mg(n = 115)	25 mg(n = 114)
Age, years	55.9 ± 8.4	54.3 ± 8.9	55.7 ± 8.5	55.3 ± 8.5	54.4 ± 10.0	55.1 ± 8.8
Male, %	65 (57.0)	65 (57.5)	67 (58.3)	65 (57.0)	56 (48.7)	69 (60.5)
Race
White	64 (56.1)	60 (53.1)	70 (60.9)	70 (61.4)	64 (55.7)	62 (54.4)
Asian	32 (28.1)	33 (29.2)	33 (28.7)	27 (23.7)	30 (26.1)	30 (26.3)
Multiracial	10 (8.8)	6 (5.3)	4 (3.5)	5 (4.4)	8 (7.0)	12 (10.5)
American Indian or Alaska Native	4 (3.5)	8 (7.1)	6 (5.2)	2 (1.8)	9 (7.8)	3 (2.6)
Black or African American	3 (2.6)	5 (4.4)	2 (1.7)	8 (7.0)	3 (2.6)	7 (6.1)
Native Hawaiian or other Pacific Islander	1 (0.9)	1 (0.9)	0 (0.0)	2 (1.8)	1 (0.9)	0 (0.0)
Ethnicity
Hispanic or Latino	34 (29.8)	30 (26.5)	35 (30.4)	24 (21.1)	31 (27.0)	37 (32.5)
Not Hispanic or Latino	80 (70.2)	83 (73.5)	80 (69.6)	90 (78.9)	84 (73.0)	77 (67.5)
Body weight, kg	82.1 ± 20.4	82.0 ± 18.8	82.5 ± 17.7	84.1 ± 17.2	82.3 ± 16.5	80.5 ± 17.5
BMI, kg/m²	29.6 ± 5.3	29.7 ± 5.5	29.9 ± 5.3	30 ± 5.1	30.4 ± 5.2	29.2 ± 5.2
Type 2 diabetes duration, years	5.8 ± 4.6	4.8 ± 4.2	5.3 ± 4.3	5.4 ± 3.9	5.1 ± 4.6	5.9 ± 5.2
Prior AHA use	58 (50.9)	59 (52.2)	59 (51.3)	59 (51.8)	59 (51.3)	59 (51.8)
HbA_1c, %	8.1 ± 0.9	8.1 ± 0.9	8.0 ± 0.9	7.9 ± 0.9	8.0 ± 0.9	8.1 ± 1.0
Range	6.6–10.4	6.0–11.3	6.0–10.4	6.7–11.7	6.4–10.7	6.4–11.0
HbA_1c, mmol/mol	65.0 ± 9.8	65.2 ± 10.1	63.8 ± 9.4	63.2 ± 9.5	64.4 ± 9.4	65.5 ± 11.1
Range	48.6–90.2	42.1–100.0	42.1–90.2	49.7–104.4	46.4–93.4	46.4–96.7
2-h PMG, mmol/L	13.4 ± 4.0	12.7 ± 3.5	12.7 ± 3.6	13.0 ± 4.5	12.9 ± 4.0	13.6 ± 4.6
FPG, mmol/L	9.6 ± 2.4	9.5 ± 2.5	9.4 ± 2.4	9.4 ± 2.4	9.3 ± 2.1	9.7 ± 2.6

Data are expressed as mean ± SD or as n (%), unless otherwise indicated.
To convert PMG or FPG in mmol/L to mg/dL, multiply by 18.

Table 2

Efficacy end points at week 12

Parameter	Placebo	Omarigliptin once weekly
Parameter	Placebo	0.25 mg	1 mg	3 mg	10 mg	25 mg
HbA_1c	n = 113	n = 113	n = 115	n = 114	n = 115	n = 114
Change from baseline
HbA_1c, %	0.14 (−0.01, 0.30)	−0.14 (−0.30, 0.01)	−0.36 (−0.51, −0.20)	−0.35 (−0.50, −0.19)	−0.53 (−0.68, −0.37)	−0.57 (−0.73, −0.42)
HbA_1c, mmol/mol	1.5 (−0.1, 3.2)	−1.5 (−3.2, 0.2)	−3.9 (−5.6, −2.2)	−3.8 (−5.5, −2.1)	−5.8 (−7.4, −4.1)	−6.3 (−8.0, −4.6)
Change vs. placebo
HbA_1c, %	—	−0.28 (−0.50, −0.06)^§	−0.50 (−0.71, −0.28)^*	−0.49 (−0.70, −0.27)^*	−0.67 (−0.88, −0.45)^*	−0.72 (−0.93, −0.50)^*
HbA_1c, mmol/mol	—	−3.1 (−5.5, −0.7)	−5.4 (−7.8, −3.1)	−5.3 (−7.7, 2.9)	−7.3 (−9.7, −4.9)	−7.8 (−10.2, −5.4)
2-h PMG, mmol/L	n = 111	n = 112	n = 113	n = 114	n = 114	n = 112
Change from baseline	0.4 (−0.1, 1.0)	−0.6 (−1.2, −0.1)	−1.4 (−2.0, −0.9)	−1.5 (−2.1, −1.0)	−1.9 (−2.4, −1.4)	−2.1 (−2.6, −1.5)
Change vs. placebo	—	−1.0 (−1.8, −0.3)^‡	−1.8 (−2.6, −1.1)^*	−1.9 (−2.7, −1.2)^*	−2.3 (−3.1, −1.5)^*	−2.5 (−3.3, −1.7)^*
FPG, mmol/L	n = 113	n = 113	n = 115	n = 114	n = 115	n = 114
Change from baseline	0.3 (−0.0, 0.6)	0.1 (−0.2, 0.4)	−0.8 (−1.1, −0.5)	−0.6 (−0.9, −0.3)	−0.5 (−0.9, −0.2)	−1.0 (−1.3, −0.7)
Change vs. placebo	—	−0.2 (−0.7, 0.2)^†	−1.1 (−1.6, −0.7)^*	−0.9 (−1.3, −0.5)^*	−0.9 (−1.3, −0.4)^*	−1.3 (−1.8, −0.9)^*

Change from baseline is the LS mean change from baseline at week 12 (95% CI). Change vs. placebo is the between-treatment difference in the LS mean change from baseline at week 12 (95% CI). To convert PMG or FPG in mmol/L to mg/dL, multiply by 18.
↵§P = 0.012 from trend test for omarigliptin vs. placebo.
↵*P < 0.001 from trend test for omarigliptin vs. placebo.
↵‡P = 0.009 from trend test for omarigliptin vs. placebo.
↵†P = 0.276 from trend test for omarigliptin vs. placebo.

Table 3

Efficacy end points at week 78

Parameter	Placebo/metformin	Omarigliptin once weekly
Parameter	Placebo/metformin	0.25/25 mg	1/25 mg	3/25 mg	10/25 mg	25 mg
HbA_1c	n = 80	n = 83	n = 91	n = 79	n = 82	n = 70
Baseline
HbA_1c, %	8.2 ± 0.9	8.1 ± 0.9	8.0 ± 0.9	7.9 ± 0.8	8.0 ± 0.9	8.0 ± 0.8
HbA_1c, mmol/mol	65.7 ± 9.9	65.4 ± 9.9	64.1 ± 9.8	62.4 ± 8.8	64.4 ± 9.4	64.2 ± 9.3
Change from baseline
HbA_1c, %	−0.73 (−1.07, −0.40)	−0.46 (−0.80, −0.13)	−0.28 (−0.61, 0.06)	−0.18 (−0.52, 0.17)	−0.35 (−0.71, 0.01)	−0.34 (−0.70, 0.03)
HbA_1c, mmol/mol	−8.0 (−11.7, −4.3)	−5.1 (−8.8, −1.4)	−3.0 (−6.7, 0.7)	−1.9 (−5.7, 1.9)	−3.9 (−7.8, 0.1)	−3.7 (−7.7, 0.3)
2-h PMG, mmol/L	n = 79	n = 83	n = 91	n = 79	n = 82	n = 70
Baseline	13.6 ± 3.9	13.0 ± 3.6	12.9 ± 3.6	12.6 ± 3.6	13.0 ± 4.3	13.3 ± 4.4
Change from baseline	−2.2 (−3.2, −1.3)	−2.1 (−3.0, −1.1)	−1.2 (−2.1, −0.2)	−1.0 (−2.0, −0.0)	−1.5 (−2.6, −0.5)	−2.4 (−3.4, −1.4)
FPG, mmol/L	n = 80	n = 83	n = 91	n = 79	n = 82	n = 70
Baseline	9.6 ± 2.4	9.5 ± 2.3	9.5 ± 2.5	9.2 ± 1.9	9.2 ± 2.3	9.6 ± 2.6
Change from baseline	−0.6 (−1.5, 0.2)	−0.2 (−1.1, 0.6)	−0.2 (−1.0, 0.6)	−0.0 (−0.9, 0.9)	−0.2 (−1.1, 0.7)	0.2 (−0.7, 1.1)

Baseline and week 78 data are presented as mean ± SD. Change from baseline is the LS mean change from baseline at week 78 (95% CI). To convert PMG or FPG in mmol/L to mg/dL, multiply by 18.