Trulicity

Glycemic Control Monotherapy Trials in Adults with Type 2 Diabetes Mellitus

• Double-blind trial with primary endpoint at 26 weeks.
• 807 adults inadequately treated with diet and exercise or with diet and exercise and 1 antidiabetic agent.
• Participants (mean age: 56 years; mean duration of type 2 diabetes: 3 years; 44% were male, 74% White, 7% Black, and 8% Asian) were randomly assigned to Trulicity 0.75mg once weekly, Trulicity 1.5mg once weekly, or metformin 1500-2000mg/day following a 2-week washout.
• Change from baseline at week 26 in HbA1c: Trulicity 0.75mg: -0.7; Trulicity 1.5mg: -0.8; metformin 1500-2000mg: -0.6.

Glycemic Control Combination Therapy Trials in Adults with Type 2 Diabetes Mellitus

• Double-blind, placebo-controlled trial with primary endpoint at 52 weeks.
• 972 adults ( mean age: 54 years; mean duration of type 2 diabetes: 7 years; 48% were male, 53% White, 4% Black, 27% Asian).
• Participants randomly assigned to Trulicity 0.75mg once weekly, Trulicity 1.5mg once weekly, or sitagliptin 100mg/day (after 26 weeks, patients in the placebo treatment group received blinded sitagliptin 100mg/day for the remainder of the trial), 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.
• At 26 weeks, the HbA1c change was 0.1% for placebo, -1.0% for Trulicity 0.75mg, -1.2% for Trulicity 1.5mg, and -0.6% for sitagliptin.
• Percentage of patients achieving HbA1c <7.0%: 22% for placebo, 56% for Trulicity 0.75mg, 62% for Trulicity 1.5mg, and 39% for sitagliptin.
• Mean weight reductions at 26 weeks: 1.4kg for placebo, 2.7kg for Trulicity 0.75mg, 3.0kg for Trulicity 1.5mg, and 1.4kg for sitagliptin.
• Mean reduction of fasting glucose: 9mg/dL for placebo, 35mg/dL for Trulicity 0.75mg, 41mg/dL for Trulicity 1.5mg, and 18mg/dL for sitagliptin.
• Compared with placebo (at 26 weeks) and sitagliptin (at 26 and 52 weeks), Trulicity 0.75mg and 1.5mg once weekly resulted in a statistically significant reduction in HbA1c, all in combination with metformin.

Dosage Ranging Trial of Trulicity 1.5mg, 3mg, and 4.5mg (Add-on to Metformin)

• Parallel-arm, double-blind trial with primary endpoint at 36 weeks.
• 1842 patients (mean age: 57.1 years; mean duration of type 2 diabetes: 7.6 years; 51.2 male, 85.8% White, 4.5% Black, 2.4% Asian).
• Participants were randomly assigned to Trulicity 1.5mg, Trulicity 3mg or Trulicity 4.5mg once weekly, all as add-on to metformin.
• Following randomization, all patients received Trulicity 0.75mg once weekly; dose was increased every 4 weeks until patients reached assigned dose.
• At 36 weeks, treatment with Trulicity 4.5mg resulted in statistically significant reduction in HbA1C (difference, -0.2 [95% CI, -0.4, -0.1]) and in body weight (difference, -1.6kg [95% CI, -2.2, -1.1]) compared with Trulicity 1.5mg.

Placebo-Controlled Trial (Add-on to Sulfonylurea)

• 24-week, placebo-controlled, double-blind trial.
• 299 adults (mean age: 58 years; mean duration of type 2 diabetes: 8 years; 44% male, 83% White, 4% Black, 2% Asian).
• Participants were randomly assigned to receive Trulicity 1.5mg once weekly or placebo, both as add-on to glimepiride.
• At 24 weeks, treatment with Trulicity 1.5mg resulted in statistically significant reduction in HbA1c compared with placebo (difference, -1.1 [95% CI, -1.4, -0.7]).

Placebo- and Exenatide-Controlled Trial (Add-on to Metformin and Thiazolidinedione) 

• Placebo-controlled trial with primary endpoint at 26 weeks.
• 976 adults (mean age: 56 years; mean duration of type 2 diabetes: 9 years; 58% male, 74% White, 8% Black, 3% Asian).
• Participants were randomly assigned to Trulicity 0.75mg once weekly, Trulicity 1.5mg once weekly, exenatide 10mcg twice daily, or placebo, all as add-on to maximally tolerated doses of metformin (≥1500mg per day) and pioglitazone (up to 45mg per day).
• During the initial 4 weeks of the lead-in period, patients were titrated to maximally tolerated doses of metformin and pioglitazone, followed by an 8 week glycemic stabilization period prior to randomization.
• At 26 weeks, treatment with Trulicity 0.75mg and 1.5mg once weekly resulted in a statistically significant reduction in HbA1c compared with placebo (difference from placebo: -0.8 for Trulicity 0.75mg and -1.1 for Trulicity 1.5mg) and compared with exenatide (difference from exenatide: -0.3 for Trulicity 0.75mg and -0.5 for Trulicity 1.5mg).

Placebo-Controlled Trial (Add-on to Sodium-Glucose Co-Transporter 2 Inhibitor (SGLT2i), With or Without Metformin)

• 24-week placebo-controlled, double-blind study.
• 423 adults (mean age: 57 years; mean duration of type 2 diabetes: 9.4 years; 50% male, 89% White, 3% Black, 0.2% Asian).
• Participants were randomly assigned to receive Trulicity 0.75mg once weekly, Trulicity 1.5mg once weekly, or placebo, as add-on to SGLT2i.
• At 24 weeks, treatment with once weekly Trulicity 0.75mg and 1.5mg resulted in a statistically significant reduction from baseline in HbA1c compared with placebo (difference from placebo: -0.7 with Trulicity 0.75mg and -0.8 with Trulicity 1.5mg).

Insulin Glargine Controlled Trial (Add-on to Metformin and Sulfonylurea)

• 807 adults (mean age: 57 years; mean duration of type 2 diabetes: 9 years; 51% male, 71% White, 1% Black, 17% Asian) randomly assigned to Trulicity 0.75mg once weekly, Trulicity 1.5mg once weekly or insulin glargine once daily (started on 10 units and adjusted), all as add-on to maximally tolerated doses of metformin and glimepiride.
• Treatment with Trulicity once weekly resulted in a reduction in HbA1c from baseline at 52 weeks when used in combination with metformin and sulfonylurea.
• Change from baseline in HbA1c: -0.8 with Trulicity 0.75mg, -1.1 with Trulicity 1.5mg, -0.6 with insulin glargine.

Placebo-Controlled Trial (Add-on to Basal Insulin, With or Without Metformin)

• 300 adults (mean age: 60 years; mean duration of type 2 diabetes: 13 years; 58% male, 94% White, 4% Black, 0.3% Asian) were randomly assigned to receive once weekly Trulicity 1.5mg or placebo, as add-on to titrated basal insulin glargine (with or without metformin).
• Mean starting dose of insulin glargine was 37 units/day for patients receiving placebo and 41 units/day for patients receiving Trulicity 1.5mg.
• At 28 weeks, treatment with once weekly Trulicity 1.5mg resulted in a statistically significant reduction in HbA1c compared with placebo (change from baseline: -1.4 vs -0.7)

Insulin Glargine-Controlled Trial (Combination with Prandial Insulin, with or without Metformin) 

• 884 adults (mean age: 59 years; mean duration of type 2 diabetes: 13 years; 54% male, 79% White, 10% Black, 4% Asian) were randomly assigned to receive Trulicity 0.75mg once weekly, Trulicity 1.5mg once weekly, or insulin glargine once daily, all in combination with prandial insulin lispro 3 times daily, with or without metformin.
• Treatment with Trulicity 0.75mg and 1.5mg once weekly resulted in a reduction in HbA1c from baseline. 
• Change from baseline in HbA1c: -1.6 with Trulicity 0.75mg, -1.6 with Trulicity 1.5mg, -1.4 with insulin glargine.

Glycemic Control Trials in Adults with Type 2 Diabetes Mellitus and Moderate to Severe Chronic Kidney Disease

• 576 adults with type 2 diabetes (mean age: 65 years; mean duration of type 2 diabetes: 18 years; 52% male, 69% White, 16% Black: 3% Asian).
• At baseline, overall mean eGFR was 38mL/min/1.73m², 30% of patients had eGFR <30mL/min/1.73m², and 45% of patients had macroalbuminuria.
• Participants were randomly assigned to receive Trulicity 0.75mg once weekly, Trulicity 1.5mg once weekly, or insulin glargine once daily, all in combination with prandial insulin lispro.
• Treatment with Trulicity 0.75mg and 1.5mg once weekly resulted in a reduction in HbA1c at 26-weeks from baseline.
• Change from baseline in HbA1c: -0.9 with Trulicity 0.75mg, -1.0 with Trulicity 1.5mg, -1.0 with insulin glargine.
• The mean body weight changes from baseline at week 26 were -1.1, -2, and 1.9kg in the Trulicity 0.75mg, Trulicity 1.5mg, and insulin glargine arms, respectively.

Cardiovascular Outcomes Trial in Adults with Type 2 Diabetes Mellitus and Cardiovascular Disease or Multiple Cardiovascular Risk Factors

• 9901 adults with type 2 diabetes and established cardiovascular (CV) disease or multiple CV risk factors (mean age: 66 years; mean duration of type 2 diabetes: 10.5 years; median baseline HbA1c: 7.2%; 46% female, 76% White, 7% Black, 4% Asian).
• During the trial, investigators were to modify antidiabetic and CV medications to achieve local standard of care treatment targets with respect to blood glucose, lipids, and blood pressure, and manage patients recovering from an acute coronary syndrome or stroke event per local treatment guidelines.
• Participants were randomly assigned to receive Trulicity 1.5mg (n=4949) or placebo (n=4952) both added to standard of care.
• Median follow-up duration: 5.4 years
• Primary endpoint: First occurrence of a composite 3-component major adverse cardiovascular event (MACE) outcome, which included CV death, nonfatal myocardial infarction (MI) and non-fatal stroke.
• Trulicity significantly reduced the risk of first occurrence of primary composite endpoint of CV death, non-fatal MI, or non-fatal stroke (hazard ratio, 0.88, 95% CI 0.79-0.99); there were 594 events in the Trulicity arm and 663 events in the placebo arm.

Glycemic Control Trial in Pediatric Patients 10 Years of Age and Older with Type 2 Diabetes Mellitus

• 154 pediatric patients 10 years of age and older with type 2 diabetes who had inadequate glycemic control despite diet and exercise were randomly assigned to receive Trulicity once weekly (0.75mg and 1.5mg) or placebo in combination with or without metformin and/or basal insulin.
• At week 26, once weekly Trulicity (0.75mg and 1.5mg, pooled) (with or without metformin and/or basal insulin) was superior to placebo (P <.001) in the change from baseline in HbA1c (difference from placebo: -1.4).