bservation carried forward (LOCF) was used to impute missing data. Data post-onset of rescue therapy are treated as missing. At Week 26, primary efficacy was imputed for 10%, 12% and 14% of individuals randomized to TRULICITY 0.75 mg, TRULICITY 1.5 mg and metformin, respectively.
14.2 Combination Therapy
Add-on to Metformin
In this 104-week placebo-controlled, double-blind study (52-week primary endpoint), 972 patients were randomized to placebo, TRULICITY 0.75 mg once weekly, TRULICITY 1.5 mg once weekly, or sitagliptin 100 mg/day (after 26 weeks, patients in the placebo treatment group received blinded sitagliptin 100 mg/day for the remainder of the study), all as add-on to metformin. Randomization occurred after an 11-week lead-in period to allow for a metformin titration period, followed by a 6-week glycemic stabilization period. Patients had a mean age of 54 years; mean duration of type 2 diabetes of 7 years; 47% were male; race: White, Black and Asian were 52%, 4% and 25%, respectively; and 26% of the study population were in the US.
At the 26 week placebo-controlled time point, the HbA1c reduction was 0.1%, 1.0%, 1.2%, and 0.6% for placebo, TRULICITY 0.75 mg, TRULICITY 1.5 mg, and sitagliptin, respectively. The percentage of patients who achieved HbA1c <7.0% was 22%, 56%, 62%, 39% for placebo, TRULICITY 0.75 mg, TRULICITY 1.5 mg, and sitagliptin, respectively. At 26 weeks, there was a mean weight reduction of 1.4 kg, 2.7 kg, 3.0 kg, and 1.4 kg for placebo, TRULICITY 0.75 mg, TRULICITY 1.5 mg, and sitagliptin, respectively. There was a mean reduction of fasting glucose of 9 mg/dL, 35 mg/dL, 41 mg/dL, and 18 mg/dL for placebo, TRULICITY 0.75 mg, TRULICITY 1.5 mg, and sitagliptin, respectively.
Treatment with TRULICITY 0.75 mg and 1.5 mg once weekly resulted in a statistically significant reduction in HbA1c compared to placebo (at 26 weeks) and compared to sitagliptin (at 26, and 52), all in combination with metformin (Table 4 and Figure 4).
Table 4: Results at Week 52 of TRULICITY Compared to Sitagliptin used as Add-On to Metformina
Abbreviations: HbA1c = hemoglobin A1c.
a All ITT patients randomized after the dose-finding portion of the study. Last observation carried forward (LOCF) was used to impute missing data. At Week 52 primary efficacy was imputed for 15%, 19%, and 20% of individuals randomized to TRULICITY 0.75 mg, TRULICITY 1.5 mg and sitagliptin, respectively.
b Least-squares (LS) mean adjusted for baseline value and other stratification factors.
‡ Subjects included in the analysis are a subset of the ITT population that had at least one post-baseline assessment. The primary analysis included 276, 277, and 270 individuals randomized to TRULICITY 0.75 mg, TRULICITY 1.5 mg and sitagliptin, respectively.
†† Multiplicity adjusted 1-sided p-value <0.001, for superiority of TRULICITY compared to sitagliptin, assessed only for HbA1c.
## p<0.001 TRULICITY compared to sitagliptin, assessed only for HbA1c <7.0%.
Figure 3: Adjusted Mean HbA1c Change at each Time Point (ITT, MMRM) and at Week 52 (ITT, LOCF)
Add-on to Metformin and Thiazolidinedione
In this 52-week placebo-controlled study (26-week primary endpoint), 976 patients were randomized to placebo, TRULICITY 0.75 mg once weekly, TRULICITY 1.5 mg once weekly, or exenatide 10 mcg BID, all as add-on to maximally tolerated doses of metformin (≥1500 mg per day) and pioglitazone (up to 45 mg per day). Exenatide treatment group assignment was open-label wh |
