Regulatory Decision Summary for Trulicity
Review decision
The Regulatory Decision Summary explains Health Canada’s decision for the product seeking market authorization. The Regulatory Decision Summary includes the purpose of the submission and the reason for the decision.
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What was the purpose of this submission?
The purpose of the submission was to add an indication for concomitant use of Trulicity with sodium glucose linked transporter-2 inhibitors in patients with type 2 diabetes mellitus and to remove the cautionary text regarding Trulicity use in patients with severe renal impairment.
Trulicity was previously authorized for the once-weekly treatment of adult patients with type 2 diabetes mellitus to improve glycemic control, in combination with:
- diet and exercise in patients for whom metformin is inappropriate due to contraindication or intolerance.
- metformin, when diet and exercise plus maximal tolerated dose of metformin do not achieve adequate glycemic control.
- metformin and a sulfonylurea, when diet and exercise plus dual therapy with metformin and a sulfonylurea do not achieve adequate glycemic control.
- basal insulin with metformin, when diet and exercise plus basal insulin with or without metformin do not achieve adequate glycemic control.
- prandial insulin with metformin, when diet and exercise plus basal or basal-bolus insulin therapy (up to two injections of basal or basal plus prandial insulin per day) with or without oral antihyperglycemic medications, do not achieve adequate glycemic control.
After evaluation of the submitted data package, Health Canada added an indication for the use of Trulicity in combination with:
- sodium glucose co-transporter 2 inhibitor (SGLT2i) with metformin, when diet and exercise plus SGLT2i with or without metformin do not achieve adequate glycemic control.
In addition, Health Canada accepted the revision of cautionary text regarding the evidence base for Trulicity use in patients with severe renal impairment.
Why was the decision issued?
Concomitant use of Trulicity with SGLT2 inhibitors
- Authorization was based on a randomized controlled trial (study GBGE) that included adult type 2 diabetes mellitus (T2DM) patients who had inadequate glycemic control (HbA1c 7.0-9.5%) on SGLT2 inhibitors with or without metformin.
- The trial included 140 patients randomized to placebo, 141 randomized to 0.75 mg Trulicity, and 142 randomized to 1.5 mg Trulicity. Patients received weekly injections of placebo or Trulicity for 24 weeks in addition to remaining on their stable baseline treatment(s) of SGLT2 inhibitors with or without metformin.
- The primary endpoint was change from baseline HbA1c for each dose level of Trulicity compared to placebo. At Week 24, the mean differences from baseline HbA1c compared to placebo were -0.79% for 1.5 mg and -0.66% for 0.75 mg Trulicity. Both Trulicity doses (0.75 mg and 1.5 mg) were superior to placebo for change from baseline HbA1c at Week 24.
- The safety profile for Trulicity was similar to the established profile when used in combination with SGLT2 inhibitors with or without metformin. The most common adverse events were nausea and diarrhea. The incidence of hypoglycemia was similar between Trulicity and placebo arms.
- The recommended initiating dose of Trulicity is 0.75 mg once weekly, administered subcutaneously. The dose may be increased to 1.5 mg once weekly for additional glycemic control. The maximum recommended dose is 1.5 mg once weekly.
- The overall benefit-risk profile of Trulicity as a concurrent therapy with metformin and SGLT2 inhibitors is positive.
Removal of cautionary text regarding Trulicity use in severe renal impairment
- Authorization was based on a randomized controlled trial that included adult patients with T2DM and moderate to severe renal impairment who had inadequate glycemic control (HbA1c 7.5-10.5%) on insulin with or without oral anti-hyperglycemic medications. Patients were switched to insulin and maintained on a stable dose during the screening period.
- The trial included 576 patients, of which 70% had moderate renal impairment and 30% of patients had severe renal impairment at baseline. Patients were stratified according to their renal status prior to randomization: 190 patients in Trulicity 0.75 mg, 192 patients in Trulicity 1.5 mg and 194 patients in insulin glargine.
- Treatment with Trulicity 0.75 mg and 1.5 mg weekly resulted in a reduction in HbA1c at 26 week from baseline (primary endpoint) that was non-inferior to insulin glargine.
- There were no new safety issues identified in this study.
The benefit/risk profile of Trulicity in adults with T2DM and moderate to severe renal impairment is considered acceptable.
Decision issued
Approved; issued a Notice of Compliance in accordance with the Food and Drug Regulations.