Drug information of dulaglutide

Mechanism of effect

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.

Pharmacodynamic

Dulaglutide activates human glucagon-like peptide-1 receptors, thus increasing intracellular cyclic AMP in beta cells. This, in turn, increases glucose-dependent insulin release. Dulaglutide also reduces glucagon secretion and slows gastric emptying.

Pharmacokinetics

Absolute bioavailability: 65% (0.75 mg/dose); 47% (1.5 mg/dose)

Peak plasma concentration: 114 ng/mL

AUC: 14,000 ng•h/mL

Vd: 19.2 L (0.75 mg/dose); 17.4 L (1.5 mg/dose)

Metabolism: Thought to be degraded into its component amino acids by general protein catabolism pathways

Half-life: 5 days

Clearance: ~0.1 L/hr

Dosage

Adult

Diabetes Mellitus Type 2

Initial: 0.75 mg SC once weekly

May increase dose to 1.5 mg once weekly for additional glycemic control

Pediatric

Safety and efficacy not established

Drug contraindications

Side effects

Interactions

Alerts

Acute pancreatitis reported (rare); after initiation of therapy, observe patients carefully for signs and symptoms of pancreatitis, including persistent severe abdominal pain, sometimes radiating to the back, which may or may not be accompanied by vomiting; discontinue if pancreatitis suspected and do not restart if confirmed

Hypoglycemia may occur when used in combination with insulin secretagogues (eg, sulfonylureas) or insulin; consider lowering sulfonylurea or insulin dosage when starting dulaglutide

Systemic hypersensitivity reactions reported; anaphylaxis and angioedema reported with other GLP-1 receptor agonists; use caution in a patient with a history of angioedema or anaphylaxis with another GLP-1 receptor agonist; unknown whether such patients will be predisposed to anaphylaxis with drug; discontinue if such reactions occur

Acute renal failure and worsening of chronic renal failure (some requiring hemodialysis) reported with treatment with glucagonlike peptide-1 (GLP-1) receptor agonists

May be associated with GI adverse reactions, sometimes severe; counsel patients to take precautions to avoid fluid depletion; has not been studied in patients with severe GI disease, including severe gastroparesis

Slows gastric emptying and may affect absorption of concomitantly administered PO drugs

Black Box Warnings

Risk of thyroid C-cell tumors

• Causes thyroid C-cell tumors in rodents; human risk could not be determined
• Contraindicated in patients with personal or family history of medullary thyroid carcinoma (MTC) or in patients with multiple endocrine neoplasia syndrome type 2 (MEN-2)
• Counsel patients regarding potential risk of MTC with therapy and inform them of symptoms of thyroid tumors (e.g., mass in the neck, dysphagia, dyspnea, persistent hoarseness); routine monitoring of serum calcitonin or using thyroid ultrasound is of uncertain value for early detection of MTC in patients receiving therapy

Points of recommendation

Follow all directions on your prescription label and read all medication guides or instruction sheets. Use the medicine exactly as directed.

Dulaglutide is injected under the skin once per week. Use dulaglutide on the same day each week at the same time of day. If you change your dosing day, allow at least 3 days to pass between doses.

You may use dulaglutide with or without food.

Use a different place each time you give an injection. Do not inject into the same place two times in a row.

Low blood sugar (hypoglycemia) can happen to everyone who has diabetes. Symptoms include headache, hunger, sweating, irritability, dizziness, nausea, fast heart rate, and feeling anxious or shaky. To quickly treat low blood sugar, always keep a fast-acting source of sugar with you such as fruit juice, hard candy, crackers, raisins, or non-diet soda.

Your doctor can prescribe a glucagon emergency injection kit to use in case you have severe hypoglycemia and cannot eat or drink. Be sure your family and close friends know how to give you this injection in an emergency.

Also watch for signs of high blood sugar (hyperglycemia) such as increased thirst or urination, blurred vision, headache, and tiredness.

Blood sugar levels can be affected by stress, illness, surgery, exercise, alcohol use, or skipping meals. Ask your doctor before changing your dose or medication schedule.

Each injection pen or prefilled syringe is for one use only. Throw away after one use, even if there is still medicine left inside. Keep it out of the reach of children and pets.

Store dulaglutide in the refrigerator, protected from light. Do not use past the expiration date on the medicine label. Do not freeze dulaglutide, and throw away the medicine if it has become frozen.

You may also store dulaglutide at room temperature for up to 14 days before use.

What happens if I miss a dose?

Use the medicine as soon as you can, but skip the missed dose if your next dose is due in less than 3 days. Do not use two doses at one time.

Do not use dulaglutide twice within a 72-hour period.

Related drugs