Trulicity (dulaglutide) - 2 indications 

Scroll down for more information on each indication: 

• to improve glycemic control in type II diabetics; approved September 2014
• for the reduction of major adverse cardiovascular events (MACE) in adults with type 2 diabetes who have established cardiovascular (CV) disease or multiple cardiovascular risk factors; approved in February 2020

General Information

Trulicity (dulaglutide) is a glucagon-like peptide (GLP-1) receptor agonist. Dulaglutide increases intracellular cyclic AMP (cAMP) in beta cells leading to glucose-dependent insulin release. Dulaglutide also decreases glucagon secretion and slows gastric emptying.

Trulicity is specifically indicated for the following:

• as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus
• for the reduction of major adverse cardiovascular events (MACE) in adults with type 2 diabetes who have established cardiovascular (CV) disease or multiple cardiovascular risk factors.

Trulicity is supplied as a solution for subcutaneous injection. The recommended initiating dose is 0.75 mg once weekly. 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. Administer Trulicity once weekly, any time of day, with or without food. Trulicity should be injected subcutaneously in the abdomen, thigh, or upper arm.

Mechanism of Action

Trulicity (dulaglutide) is a human GLP-1 receptor agonist with 90% amino acid sequence homology to endogenous human GLP-1 (7-37). Dulaglutide activates the GLP-1 receptor, a membrane-bound cell-surface receptor coupled to adenylyl cyclase in pancreatic beta cells. Dulaglutide increases intracellular cyclic AMP (cAMP) in beta cells leading to glucose-dependent insulin release. Dulaglutide also decreases glucagon secretion and slows gastric emptying.

Side Effects

Adverse effects associated with the use of Trulicity may include, but are not limited to, the following:

• nausea
• diarrhea
• vomiting
• abdominal pain
• decreased appetite

The Trulicity drug label comes with the following Black Box Warning: Dulaglutide causes thyroid C-cell tumors in rats. It is unknown whether Trulicity causes thyroid C-cell tumors, including medullary thyroid carcinoma (MTC), in humans as the human relevance of dulaglutide-induced rodent thyroid C-cell tumors has not been determined. Trulicity is contraindicated in patients with a personal or family history of MTC and in patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2). Counsel patients regarding the potential risk of MTC and symptoms of thyroid tumors.

Indication 1 - to improve glycemic control in type II diabetics

approved September 2014

Clinical Trial Results

The FDA approval of Trulicity was based on the AWARD studies. 

• AWARD-1 was a 52-week, randomized, placebo-controlled study evaluating the effects of Trulicity 1.5 mg (N=279; baseline A1C 8.1%) or 0.75 mg (N=280; baseline A1C 8.1%) and Byetta (N=276; baseline A1C 8.1%) versus placebo (N=141; baseline A1C 8.1%) on glycemic control in adults with type 2 diabetes on maximally tolerated metformin and Actos. Patients were excluded based on previous use of a GLP-1 receptor agonist or chronic insulin therapy. The primary objective was to demonstrate superiority of once-weekly Trulicity 1.5 mg versus placebo at 26 weeks (change from baseline). At the 26-week primary endpoint, mean A1C reductions were Trulicity 1.5 mg: 1.5%; Trulicity 0.75 mg: 1.3%; Byetta: 1.0%; placebo: 0.5%.
• AWARD-2 was a 78-week, randomized, open-label study evaluating the effects of Trulicity 1.5 mg (N=273; baseline A1C 8.2%) or 0.75 mg (N=272; baseline A1C 8.1%) and Lantus (N=262; baseline A1C 8.1%) on glycemic control in adults with type 2 diabetes on maximally tolerated doses of metformin and glimepiride. Patients were excluded based on previous use of a GLP-1 receptor agonist or chronic insulin therapy. The primary objective was to demonstrate the noninferiority of once-weekly Trulicity 1.5 mg versus Lantus titrated to target on A1C at 52 weeks (change from baseline). At the 52-week primary endpoint, mean A1C reductions were Trulicity 1.5 mg: 1.1%; Trulicity 0.75 mg: 0.8%; Lantus: 0.6%.
• AWARD-3 was a 52-week, randomized, double-blind study evaluating the effects of Trulicity 1.5 mg (N=269; baseline A1C 7.6%) or 0.75 mg (N=270; baseline A1C 7.6%) and metformin (N=268; baseline A1C 7.6%) on glycemic control in adults with early type 2 diabetes. Patients were excluded based on previous use of a GLP-1 receptor agonist or chronic insulin therapy. The primary objective of the study was to demonstrate the noninferiority of monotherapy with once-weekly Trulicity 1.5 mg versus metformin on A1C at 26 weeks (change from baseline). At the 26-week primary endpoint, mean A1C reductions were Trulicity 1.5 mg: 0.8%; Trulicity 0.75 mg: 0.7%; metformin: 0.6%.
• AWARD-4 was a 52-week randomized, open-label comparator study (double-blind with respect to Trulicity dose assignment) evaluating the effects of Trulicity 1.5 mg (N=295; baseline A1C 8.5%)  or 0.75 mg (N=293; baseline A1C 8.4%) and Lantus (N=296; baseline A1C 8.5%), both in combination with insulin lispro, with or without metformin, in adults with type 2 diabetes. Patients had to be treated for three months previously with stable doses of a conventional insulin regimen and were excluded based on previous use of a GLP-1 receptor agonist. The primary objective was to demonstrate the noninferiority of once-weekly Trulicity 1.5 mg versus Lantus titrated to target, both in combination with insulin lispro, with or without metformin, on A1C at 26 weeks (change from baseline). At the 26-week primary endpoint, mean A1C reductions were Trulicity 1.5 mg: 1.6%; Trulicity 0.75 mg: 1.6%; Lantus: 1.4%.
• AWARD-5 was a 104-week, placebo-controlled, randomized, double-blind study comparing the effects of Trulicity 1.5 mg (N=279; baseline A1C 8.1%), 0.75 mg (N=281; baseline A1C 8.2%) and Januvia (N=273; baseline A1C 8.0%) on glycemic control in adults with type 2 diabetes on metformin. Patients were excluded based on previous use of a GLP-1 receptor agonist or insulin therapy. The primary objective was to demonstrate the noninferiority of once-weekly Trulicity 1.5 mg versus Januvia on A1C at 52 weeks (change from baseline). At the 52-week primary endpoint, mean A1C reductions were Trulicity 1.5 mg: 1.1%; Trulicity 0.75 mg: 0.9%; Januvia: 0.4%.

Indication 2 - for the reduction of major adverse cardiovascular events (MACE) in adults with type 2 diabetes who have established cardiovascular (CV) disease or multiple cardiovascular risk factors

approved in February 2020

Clinical Trial Results

The FDA approval of Trulicity for the reduction of MACE was based on REWIND (Researching cardiovascular Events with a Weekly INcretin in Diabetes), a multicenter, randomized, double-blind, placebo-controlled trial designed to assess the effect of Trulicity 1.5 mg compared to placebo, both added to standard of care, on cardiovascular (CV) events in adults with type 2 diabetes. The primary CV outcome was the first occurrence of MACE (the composite of CV death or nonfatal myocardial infarction or nonfatal stroke). REWIND showed a significant risk reduction in MACE, a composite endpoint of nonfatal myocardial infarction (heart attack), nonfatal stroke or CV death. Results demonstrated consistent MACE risk reduction with Trulicity across major demographic and disease subgroups.