Dulaglutide
Dulaglutide (Trulicity)
Dulaglutide (brand name Trulicity) is a long-acting GLP-1 receptor agonist peptide approved for the treatment of type 2 diabetes mellitus and cardiovascular risk reduction. It is a fusion protein consisting of two GLP-1 analog sequences linked to a modified IgG4 Fc fragment, enabling once-weekly subcutaneous dosing. It is also used off-label and in clinical research for weight management and metabolic syndrome.
Mechanism of Action
Dulaglutide binds and activates the glucagon-like peptide-1 (GLP-1) receptor, a G protein-coupled receptor expressed on pancreatic beta cells, the hypothalamus, and other tissues. Activation stimulates glucose-dependent insulin secretion, suppresses inappropriate glucagon release, slows gastric emptying, and reduces appetite via central hypothalamic pathways. Its IgG4 Fc fusion design extends its half-life to approximately 5 days, enabling once-weekly administration while maintaining sustained receptor activation.
Evidence by Health Goal(17 goals)
Dosing Protocols
Any time of day, with or without food; administer on the same day each week
Starting dose is typically 0.75mg once weekly for at least 4 weeks, then titrated to 1.5mg weekly. Further escalation to 3mg and 4.5mg (maximum approved dose) can occur in 4-week intervals based on glycemic response and tolerability. Administered via prefilled auto-injector pen into the abdomen, thigh, or upper arm.
Safety & Side Effects
Dulaglutide has a well-characterized safety profile from large cardiovascular outcomes trials (REWIND), but carries FDA black box warnings regarding thyroid C-cell tumor risk observed in rodents (clinical relevance uncertain); it is contraindicated in patients with a personal or family history of medullary thyroid carcinoma or MEN2. It is a prescription-only medication in all major jurisdictions and should not be used in type 1 diabetes or diabetic ketoacidosis.
Possible Side Effects
- !Nausea (most common, particularly during initiation and dose escalation)
- !Diarrhea (typically transient, occurring early in treatment)
- !Vomiting (dose-dependent, more common at higher doses)
- !Decreased appetite and early satiety
- !Abdominal pain or discomfort
- !Injection site reactions (redness, bruising, pruritus)
- !Fatigue and asthenia
- !Increased resting heart rate (mean increase of 2-3 bpm)
Interactions
- -Delays gastric emptying — may reduce rate and extent of absorption of oral medications requiring rapid GI uptake (e.g., oral contraceptives, antibiotics); timing of co-administration should be considered
- -Additive hypoglycemic risk when combined with insulin or sulfonylureas — dose reduction of the concomitant agent is often required
- -May potentiate hypoglycemia risk in combination with other antidiabetic agents including SGLT2 inhibitors and meglitinides
- -Warfarin (and other anticoagulants): altered gastric emptying may affect INR — more frequent monitoring recommended during initiation or dose changes
- -Alcohol: may increase hypoglycemia risk, especially in patients on concurrent insulin or secretagogues
Cost & Where to Buy
Dulaglutide is a prescription-only branded pharmaceutical (Trulicity, Eli Lilly); no generic is currently available in the US. List price is approximately $900-$1000/month for four prefilled pens (4-week supply). With insurance or manufacturer savings cards, out-of-pocket cost may be reduced significantly. No legitimate research-peptide equivalent is available.
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