Dulaglutide

Summary

Dulaglutide (Trulicity) is a once-weekly injectable GLP-1 receptor agonist approved for the treatment of type 2 diabetes mellitus and for cardiovascular risk reduction in adults with type 2 diabetes with established cardiovascular disease or multiple cardiovascular risk factors. It improves glycemic control, promotes modest weight loss, and has demonstrated significant cardiovascular benefits in the REWIND trial.

Mechanism of Action

Dulaglutide is a long-acting GLP-1 receptor agonist that stimulates insulin secretion in a glucose-dependent manner, suppresses glucagon secretion, slows gastric emptying, and reduces appetite via central and peripheral mechanisms. It is an Fc fusion protein consisting of two GLP-1 analog sequences linked to a modified IgG4 Fc fragment, extending its half-life to approximately 5 days.

Routes of Administration

Goals & Uses

• Weight managementBody CompositionModerate
• Blood pressure reductionCardiovascularModerate
• Cardiovascular risk reductionCardiovascularHigh
• Renal protectionRenalModerate
• Glycemic control in type 2 diabetesMetabolicHigh

Contraindications

• Personal or family history of medullary thyroid carcinomaOncologicHigh
• Diabetic ketoacidosisMetabolicHigh
• Hypersensitivity to dulaglutide or excipientsImmunologicalHigh
• Type 1 diabetes mellitusEndocrineHigh
• Multiple Endocrine Neoplasia syndrome type 2 (MEN 2)Genetic/EndocrineHigh

Adverse Effects

• PancreatitisGastrointestinalRareInflammation of the pancreas
• HypoglycemiaMetabolicUncommonAbnormally low blood glucose
• Injection site reactionsLocalUncommon
• NauseaGastrointestinalCommonFeeling of sickness or urge to vomit
• VomitingGastrointestinalCommonForceful expulsion of stomach contents
• DiarrheaGastrointestinalCommonLoose or frequent stools

Drug Interactions

• Insulin and insulin secretagogues (e.g., sulfonylureas)High
• WarfarinModerate
• Oral medications with narrow therapeutic indexModerate

Population Constraints

• PregnancyReproductive SafetyRelative
• Pediatric patients (under 18 years)AgeRelative
• Severe renal impairment (eGFR <15 mL/min/1.73m²)RenalRelative
• Severe gastrointestinal diseaseGastrointestinalRelative
• Patients with prior pancreatitisPancreaticRelative

Regulatory Status

• European UnionApprovedApproved: Type 2 diabetes mellitus in adults as add-on to diet and exerciseEMA approved November 2014. Marketing authorization held by Eli Lilly. CV indication also recognized within EU labeling.
• United StatesApprovedApproved: Type 2 diabetes mellitus (adjunct to diet and exercise), Reduction of major adverse cardiovascular events in adults with T2D with established CVD or multiple CV risk factorsFDA approved September 2014; CV indication added May 2020. Available as 0.75 mg and 1.5 mg weekly doses; 3 mg and 4.5 mg doses added in 2020.
• United KingdomApprovedApproved: Type 2 diabetes mellitus in adultsNICE-approved with conditions; recommended as option for T2D particularly where CV risk reduction is relevant. Post-Brexit UK authorization maintained.

FDA approved in September 2014 for type 2 diabetes; expanded indication in 2020 for cardiovascular risk reduction. Also approved by EMA. Not approved for type 1 diabetes or as a weight-loss agent in isolation.

Evidence & Sources

No sources recorded yet.