A1C Goal Attainment with Initial Dual Therapy with Metformin (MET)/Sitagliptin (SITA) Compared with Met Monotherapy—Impact of Baseline A1C and Target A1C

Abstract

While MET is generally recommended as initial pharmacologic therapy for T2D, the substantial proportion of patients who do not achieve glycemic targets with monotherapy argues for initial use of dual therapy in patients with high A1C levels (e.g., >7.5% per AACE and >9.0% per ADA guidelines). The individualization of glycemic targets based on patient characteristics adds an additional complexity to treatment decision-making. This analysis was designed to identify the baseline A1C range from which patients benefitted the most with initial dual therapy (compared with monotherapy) across a range of A1C goals. Data from 3 randomized clinical trials containing treatment arms of both initial MET monotherapy (1700-2000 mg qd, n=778) and initial MET + SITA dual therapy (1700-2000 mg + 100 mg qd, n=789) were pooled. Patients in all 3 trials had an entry A1C of at least 7.5% (mean = 9.4% in both groups). Demographic and disease-related baseline characteristics were well balanced in both groups. Rates of achieving various A1C goals after 18-24 weeks of treatment were assessed across a range of baseline A1C, and odds ratios for goal attainment were calculated (Table). Initial combination therapy with MET + SITA was generally more effective than MET monotherapy in achieving treatment targets across a broad range of individualized glycemic goals and baseline A1C values. Post-treatment A1C goalGoal achieved, % (n/n) MET/SITA, N = 789Goal achieved, % (n/n) MET, N = 778Odds ratio (95% CI)Baseline A1C 7 - 7.5%< 6.5%74.1 (43/58)44.8 (26/58)1.9 (1.27, 2.78)< 7.0%91.4 (53/58)75.9 (44/58)1.8 (1.06, 3.18)Baseline A1C 7.5 - 8%< 6.5%60.7 (65/107)31.8 (41/129)1.8 (1.39, 2.38)< 7.0%82.2 (88/107)65.9 (85/129)1.5 (1.14, 2.11)< 7.5%90.7 (97/107)80.6 (104/129)1.5 (1.03, 2.26)Baseline A1C 8 - 8.5%< 6.5%43.2 (54/125)24.8 (27/109)1.5 (1.15, 2.01)< 7.0%69.6 (87/125)47.7 (52/109)1.6 (1.21, 2.07)< 7.5%81.6 (102/125 )66.1 (72/109)1.5 (1.12, 2.04)< 8.0%89.6 (112/125)80.7 (88/109)1.4 (0.99, 2.08)Baseline A1C 8.5 - 9%< 6.5%46.5 (47/101)17.4 (16/92)2.0 (1.46, 2.84)< 7.0%67.3 (68/101)41.3 (38/92)1.7 (1.28, 2.30)< 7.5%80.2 (81/101)60.9 (36/92)1.6 (1.17, 2.23)< 8.0%86.1 (87/101)77.2 (71/92)1.4 (0.93, 1.97)Baseline A1C 9 - 9.5%< 6.5%32.2 (29/90)15.9 (13/82)1.6 (1.10, 2.30)< 7.0%52.2 (47/90)32.9 (27/82)1.5 (1.09, 2.03)< 7.5%71.1 (64/90)58.5 (48/82)1.3 (0.96, 1.81)< 8.0%82.2 (74/90)75.6 (62/82)1.2 (0.84, 1.77)Baseline A1C 9.5- 10%< 6.5%32.8 (21/64)15.1 (11/73)1.7 (1.10, 2.51)< 7.0%53.1 (34/64)23.3 (17/73)1.9 (1.34, 2.79)< 7.5%60.9 (39/64)35.6 (26/73)1.7 (1.19, 2.38)< 8.0%68.8 (44/64)50.7 (37/73)1.5 (1.03, 2.08)Baseline A1C >10.0%< 6.5%19.0 (46/242)11.3 (26/230)1.4 (1.05, 1.76)< 7.0%32.6 (79/242)22.6 (52/230)1.3 (1.05, 1.58)< 7.5%44.6 (108/242)33.9 (78/230)1.3 (1.04, 1.51)< 8.0%56.6 (137/242)42.6 (98/230)1.3 (1.10, 1.59) Disclosure A. Raji: Employee; Self; Merck & Co., Inc. M.C. Ellison: Employee; Self; Merck & Co., Inc. R.L.H. Lam: Employee; Self; Merck & Co., Inc. E.A. O'Neill: Employee; Self; Merck & Co., Inc. S.S. Engel: Employee; Self; Merck & Co., Inc.. Stock/Shareholder; Self; Merck & Co., Inc..