In male and female rats, dulaglutide causes a dose-related and treatment-duration-dependent increase in the incidence of thyroid C-cell tumors (adenomas and carcinomas) after lifetime exposure. It is unknown whether dulaglutide causes thyroid C-cell tumors, including medullary thyroid carcinoma (MTC), in humans as human relevance of dulaglutide-induced rodent thyroid C-cell tumors has not been determined.
Dulaglutide 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 with use of dulaglutide and inform them of symptoms of thyroid tumors (eg, mass in the neck, dysphagia, dyspnea, persistent hoarseness). Routine monitoring of serum calcitonin or using thyroid ultrasound monitoring is of uncertain value for early detection of MTC in patients treated with dulaglutide.
Note: Due to lack of additive glycemic benefit, avoid concomitant use with a dipeptidyl peptidase-4 inhibitor (ADA/EASD [Davies 2018]). May require a dose reduction of insulin and/or insulin secretagogues (sulfonylureas, meglitinides) to avoid hypoglycemia (AACE/ACE [Garber 2020]).
Diabetes mellitus, type 2, treatment:
Note: May be used as an adjunctive agent or alternative monotherapy for select patients, including those in whom initial therapy with lifestyle intervention and metformin failed, or who cannot take metformin. May be preferred in patients who have or are at risk for atherosclerotic cardiovascular disease, when weight loss is desired, and/or in patients with an HbA1c relatively far from goal (eg, HbA1c 9% to 10%) and type 1 diabetes is not likely (ADA 2021; Gerstein 2019; Wexler 2020).
SubQ: Initial: 0.75 mg once weekly; may increase to 1.5 mg once weekly after 4 to 8 weeks if needed to achieve glycemic goals (Dungan 2021; Umpierrez 2014; Weinstock 2015). If additional glycemic control is needed, may further increase to 3 mg once weekly after at least 4 weeks on the 1.5 mg weekly dose and then to a maximum of 4.5 mg once weekly after at least 4 weeks on the 3 mg weekly dose.
Missed doses: Missed dose should be administered as soon as possible within 3 days; resume usual schedule thereafter. If there are <3 days until next scheduled dose, omit the missed dose and resume administration at the next scheduled weekly dose.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.
Altered kidney function: Mild to severe impairment: No dosage adjustment necessary (manufacturer's labeling). Use caution when initiating or escalating doses; new onset or worsening of existing renal failure has been reported, most commonly in patients experiencing volume depletion from GI losses (eg, vomiting, diarrhea, dehydration).
Hemodialysis, intermittent (thrice weekly): Unlikely to be dialyzable (expert opinion): No supplemental dose or dosage adjustment necessary; use with caution due to limited clinical evidence (manufacturer's labeling).
Peritoneal dialysis: Unlikely to be dialyzable (expert opinion): No dosage adjustment necessary; use with caution due to limited clinical evidence (manufacturer's labeling).
There are no dosage adjustments provided in the manufacturer's labeling; use with caution.
Refer to adult dosing.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution Pen-injector, Subcutaneous [preservative free]:
Trulicity: 0.75 mg/0.5 mL (0.5 mL); 1.5 mg/0.5 mL (0.5 mL); 3 mg/0.5 mL (0.5 mL); 4.5 mg/0.5 mL (0.5 mL) [contains polysorbate 80]
No
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution Pen-injector, Subcutaneous:
Trulicity: 0.75 mg/0.5 mL (0.5 mL); 1.5 mg/0.5 mL (0.5 mL) [contains polysorbate 80]
An FDA-approved patient medication guide, which is available with the product information and at https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/125469s044lbl.pdf#page=27, must be dispensed with this medication.
SUBQ: Do not inject intravenously or intramuscularly. Inject subcutaneously into the upper arm, thigh, or abdomen; when administering within the same body region, use a different injection site each week. Administer once weekly on the same day each week, without regard to meals or time of day. The day of weekly administration may be changed, as long as the last dose was administered ≥3 days before. If using concomitantly with insulin, administer as separate injections (do not mix); may inject in the same body region as insulin, but not adjacent to one another. Dulaglutide is a single-dose device that does not require priming before injection (Romera 2019; manufacturer’s labeling).
Diabetes mellitus, type 2, treatment: As an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus; risk reduction of major cardiovascular events (cardiovascular death, nonfatal myocardial infarction, nonfatal stroke) in adults with type 2 diabetes mellitus who have established cardiovascular disease or multiple cardiovascular risk factors.
Trulicity may be confused with Tanzeum [DSC], Toujeo, Tradjenta, Tresiba
Acute kidney injury (AKI), which sometimes requires dialysis, has been reported with dulaglutide and other glucagon-like peptide 1 receptor agonists. According to the manufacturer, AKI secondary to dulaglutide was seen mostly in patients who had experienced nausea, vomiting, diarrhea, or dehydration. In a post-hoc analysis of multiple clinical trials, dulaglutide was not associated with an increase in adverse effects reflecting potential acute kidney failure (Ref).
Mechanism: Non–dose-related; exact mechanism is unknown. Pre-renal AKI may occur due to dehydration and volume contraction secondary to gastrointestinal symptoms (eg, nausea, vomiting, diarrhea) (Ref).
Onset: Varied; because the mechanism is thought to be related to volume contraction, timing may be dependent on GI symptoms, initiation or dosage adjustment of concomitant medications, and/or comorbid conditions (Ref).
Risk factors:
• Volume contraction (eg, during periods of severe vomiting or diarrhea) (Ref)
• Co-administration of medications known to result in kidney injury during episodes of dehydration (eg, drugs that inhibit the renin-angiotensin system) (Ref)
• Preexisting kidney impairment
An increased incidence of diabetic retinopathy (DR) was noted during the REWIND study, a clinical trial evaluating the impact of dulaglutide on cardiovascular outcomes in patients with type 2 diabetes (Ref); the proportion of patients with DR complications was larger among patients with a prior history of DR. In addition, rapid reductions in HbA1c are associated with an early worsening of DR (Ref); in an analysis of DR complications due to another glucagon-like peptide 1 (GLP-1) receptor agonist (semaglutide), the increased risk of DR was mainly observed in patients with preexisting DR and primarily attributable to the magnitude and rapidity of reduction in HbA1c (Ref). Clinicians should note that this effect has been observed with SUBQ dulaglutide, exenatide, and semaglutide but not other GLP-1 receptor agonists (Ref).
Mechanism: Unknown; in general, worsening of preexisting DR is a known consequence of rapid improvement of hyperglycemia, especially in patients with uncontrolled diabetes (Ref). Although unlikely, a direct toxic effect or potential angiogenic action of dulaglutide has not been ruled out (Ref).
Onset: Varied; clinicians should note that DR is a progressive condition and the onset of DR complications may vary.
Risk factors:
• Preexisting diabetic retinopathy
• In general, the risk of early worsening of DR is increased when intensive treatment is initiated in patients with long-standing poor glycemic control (Ref)
Cholelithiasis, acute cholecystitis, and cholestasis have been reported with dulaglutide therapy (Ref); gallbladder disease secondary to glucagon-like peptide 1 (GLP-1) receptor agonists, including dulaglutide, has required hospitalization or cholecystectomy (Ref). Resolution of biliary stones following discontinuation has been documented with other GLP-1 receptor agonists (eg, liraglutide) (Ref); one patient with dulaglutide-associated cholecystitis successfully continued dulaglutide therapy post-cholecystectomy without recurrent complications (Ref).
Mechanism: Non–dose-related; not fully understood. Animal studies and in vitro data have demonstrated that GLP-1 enhances the proliferation and functional activity of cholangiocytes, which may result in gallbladder diseases (Ref). Some authors have postulated a change in bile acid production and secretion, decreased gallbladder emptying, prolonged gallbladder refilling, weight loss, or potentially a combination of these factors (Ref).
Onset: Not well defined. In one case report, acute cholecystitis developed after 16 months of treatment with dulaglutide (Ref).
GI effects, mainly diarrhea, nausea, and vomiting, are the most common adverse reactions associated with glucagon-like peptide 1 (GLP-1) receptor agonists, including dulaglutide (Ref). Symptoms may sometimes be severe. Abdominal pain, decreased appetite, and dyspepsia may also occur. GI effects tend to occur during dose escalation and decrease over time (Ref); may result in treatment discontinuation.
In general, long-acting GLP-1 receptor agonists (eg, dulaglutide, once-weekly exenatide, liraglutide, semaglutide) are associated with less nausea and vomiting but more diarrhea when compared to their short-acting counterparts (Ref). Dulaglutide may be associated with a lower risk of diarrhea when compared to liraglutide (Ref). In the SUSTAIN-7 trial comparing once-weekly semaglutide to once-weekly dulaglutide, rates of gastrointestinal effects were similar for both doses of semaglutide (0.5 mg and 1 mg) and high-dose dulaglutide (1.5 mg) (Ref).
Mechanism: Dose-related; however, the exact mechanism is not fully understood. May be a result of delayed gastric emptying or activation of centers involved in appetite regulation, satiety, and nausea (Ref).
Onset: Intermediate; nausea, vomiting, and diarrhea are most common soon after initiation (eg, the first 4 weeks of treatment) and during dose escalation (Ref). In a post-hoc analysis of 2 clinical trials, GI effects were most common during the first 2 weeks of treatment and the incidence declined rapidly thereafter (Ref).
Risk factors:
• Dose; generally greater with higher doses
• In general, rapid titration of GLP-1 receptor agonists is associated with a higher risk of GI symptoms
Serious, immediate hypersensitivity reactions, including anaphylaxis and angioedema, have been reported with glucagon-like peptide 1 (GLP-1) receptor agonists (Ref). Exendin-based GLP-1 receptor agonists (eg, exenatide, lixisenatide) are associated with a doubling of reporting odds of anaphylactic reaction compared with human-analogue GLP-1 receptor agonists (eg, liraglutide, dulaglutide, albiglutide, semaglutide) (Ref).
Delayed hypersensitivity reactions such as a morbilliform rash (Ref) and injection site reactions (Ref) have been documented.
Mechanism: Non–dose-related; immunologic.
Immediate hypersensitivity reactions: IgE-antibodies are formed against a drug allergen following initial exposure (Ref).
Delayed hypersensitivity reactions: T-cell mediated (Ref).
Note: The risk of immune-mediated adverse effects is low with dulaglutide, despite the formation of neutralizing antibodies (Ref).
Onset:
Immediate hypersensitivity reactions: Rapid; generally occur within 1 hour of administration but may occur up to 6 hours after exposure (Ref).
Delayed hypersensitivity reactions: Variable; typically maculopapular (morbilliform, exanthematous) eruptions occur 4 to 14 days after drug initiation (Ref), although has been reported up to 5 weeks after starting dulaglutide (Ref).
Risk factors:
• Cross-reactivity between GLP-1 receptor agonists is unknown (Ref). Until further studies are available, dulaglutide should be used with caution in patients with a history of anaphylaxis or angioedema to other GLP-1 receptor agonists. Skin tests have been used in patients with histories of immediate hypersensitivity reactions to GLP-1 receptor agonists (Ref).
In the early stages of drug development, thyroid C-cell tumors were noted to have developed during animal studies with dulaglutide. It is unknown whether dulaglutide causes thyroid C-cell tumors in humans, as the human relevance of dulaglutide-induced rodent thyroid C-cell tumors has not been determined. According to the manufacturer, one human cases of medullary thyroid carcinoma (MTC) was reported with dulaglutide during clinical trials in a patient with pretreatment calcitonin levels ~8 times the upper limit of normal. In addition, a single case of C-cell hyperplasia with elevated calcitonin levels was noted during the REWIND trial (Ref).
Mechanism: Unknown. Animal studies have shown dose-dependent and treatment duration-dependent harmful effects in rodents but not primates, thereby indicating that proliferative C-cell effects of glucagon-like peptide 1 (GLP-1) receptor agonists may be rodent-specific. Humans have far fewer C-cells than rodents, and expression of the GLP-1 receptor in human C-cells is very low (Ref).
Risk factors:
• Patients with a personal or family history of MTC or patients with multiple endocrine neoplasia syndrome type 2 (MEN 2) may be at an increased risk
Cases of acute pancreatitis (including hemorrhagic pancreatitis and necrotizing pancreatitis with some fatalities), chronic pancreatitis, and pancreatic adenocarcinoma have been reported with use of incretin-based therapies (eg, dipeptidyl peptidase 4 [DPP-4] inhibitors, glucagon-like peptide 1 [GLP-1] receptor agonists) (Ref). Acute pancreatitis was observed with dulaglutide at rates similar to placebo during the AWARD trial program and the REWIND trial (Ref).
Mechanism: Causality has not been firmly established (Ref). GLP-1 receptor agonists directly stimulate GLP-1 receptors in pancreatic islet beta cells and exocrine duct cells which may cause an overgrowth of the cells that cover the smaller ducts, thereby resulting in hyperplasia, increased pancreatic weight, duct occlusion, back pressure, and subsequent acute or chronic pancreatic inflammation (Ref).
Onset: Not well characterized.
Risk factors:
• Patients with a prior history of pancreatitis may be at an increased risk for acute pancreatitis
• Patients with acute pancreatitis due to any cause are at an increased risk for progression to recurrent acute pancreatitis and then to chronic pancreatitis; patients with chronic pancreatitis are at an increased risk for pancreatic cancer (Ref).
• Risk factors for pancreatitis due to any cause include, but are not limited to, hypertriglyceridemia, cholelithiasis, alcohol use, and obesity (Ref)
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions reported in adults.
>10%:
Endocrine & metabolic: Hypoglycemia (≤77%; highest incidence seen with adjunctive use of insulin or sulfonylureas; severe hypoglycemia: ≤3%; highest incidence seen with adjunctive use of prandial insulin)
Gastrointestinal: Diarrhea (9% to 13%) (table 1) , nausea (12% to 21%) (table 2) , vomiting (6% to 13%) (table 3)
Drug (Dulaglutide) |
Placebo |
Dose |
Number of Patients (Dulaglutide) |
Number of Patients (Placebo) |
---|---|---|---|---|
13% |
7% |
1.5 mg once weekly |
834 |
568 |
9% |
7% |
0.75 mg once weekly |
836 |
568 |
Drug (Dulaglutide) |
Placebo |
Dose |
Number of Patients (Dulaglutide) |
Number of Patients (Placebo) |
---|---|---|---|---|
21% |
5% |
1.5 mg once weekly |
834 |
568 |
12% |
5% |
0.75 mg once weekly |
836 |
568 |
Drug (Dulaglutide) |
Placebo |
Dose |
Number of Patients (Dulaglutide) |
Number of Patients (Placebo) |
---|---|---|---|---|
13% |
2% |
1.5 mg once weekly |
834 |
568 |
6% |
2% |
0.75 mg once weekly |
836 |
568 |
1% to 10%:
Cardiovascular: First degree atrioventricular block (2%), prolongation P-R interval on ECG (3%), sinus tachycardia (6%), sustained tachycardia (2%)
Endocrine & metabolic: Diabetic retinopathy (2%; more common in patients with history of diabetic retinopathy at baseline) (table 4)
Drug (Dulaglutide) |
Placebo |
Dose |
Indication |
Comments |
---|---|---|---|---|
1.9% |
1.5% |
1.5 mg once weekly |
Type 2 diabetes with established cardiovascular disease or multiple cardiovascular risk factors |
N/A |
9% |
6% |
1.5 mg once weekly |
Type 2 diabetes with established cardiovascular disease or multiple cardiovascular risk factors |
Patients with a history of diabetic retinopathy at baseline |
1% |
1% |
1.5 mg once weekly |
Type 2 diabetes with established cardiovascular disease or multiple cardiovascular risk factors |
Patients without a known history of diabetic retinopathy |
Gastrointestinal: Abdominal distension (2% to 3%), abdominal pain (7% to 9%) (table 5) , constipation (4%), decreased appetite (5% to 9%) (table 6) , dyspepsia (4% to 6%) (table 7) , eructation (2%), flatulence (3%), gastroesophageal reflux disease (2%)
Drug (Dulaglutide) |
Placebo |
Dose |
Number of Patients (Dulaglutide) |
Number of Patients (Placebo) |
---|---|---|---|---|
9% |
5% |
1.5 mg once weekly |
834 |
568 |
7% |
5% |
0.75 mg once weekly |
836 |
568 |
Drug (Dulaglutide) |
Placebo |
Dose |
Number of Patients (Dulaglutide) |
Number of Patients (Placebo) |
---|---|---|---|---|
9% |
2% |
1.5 mg once weekly |
834 |
568 |
5% |
2% |
0.75 mg once weekly |
836 |
568 |
Drug (Dulaglutide) |
Placebo |
Dose |
Number of Patients (Dulaglutide) |
Number of Patients (Placebo) |
---|---|---|---|---|
6% |
2% |
1.5 mg once weekly |
834 |
568 |
4% |
2% |
0.75 mg once weekly |
836 |
568 |
Immunologic: Antibody development (2%; neutralizing: <1%)
Nervous system: Fatigue (4% to 6%)
<1%:
Gastrointestinal: Pancreatitis
Hypersensitivity: Hypersensitivity reaction
Local: Injection site reaction
Frequency not defined: Gastrointestinal: Increased serum amylase, increased serum lipase
Postmarketing:
Dermatologic: Morbilliform rash (Rzepka 2020)
Gastrointestinal: Acute pancreatitis (Gerstein 2019), cholecystitis (Butler 2021) (table 8) , cholelithiasis (Gerstein 2019; Pratley 2018), cholestasis
Drug (Dulaglutide) |
Placebo |
Comments |
---|---|---|
0.5% |
0.3% |
Serious events of acute cholecystitis |
Hepatic: Hepatitis, increased liver enzymes
Hypersensitivity: Anaphylaxis (Milicevic 2016), angioedema (Milicevic 2016)
Renal: Acute kidney injury (Tuttle 2017)
Serious hypersensitivity to dulaglutide or any component of the formulation; personal or family history of medullary thyroid carcinoma (MTC); patients with multiple endocrine neoplasia syndrome type 2 (MEN2)
Canadian labeling: Additional contraindications (not in US labeling): Pregnancy; breast-feeding
Disease-related concerns:
• Bariatric surgery:
- Dehydration: Evaluate, correct, and maintain postsurgical fluid requirements and volume status prior to initiating therapy, and closely monitor the patient for the duration of therapy; acute and chronic kidney failure exacerbation may occur. A majority of cases occurred in patients with nausea, vomiting, diarrhea, and/or dehydration. Nausea is common and fluid intake may be more difficult after gastric bypass, sleeve gastrectomy, and gastric band (Mechanick 2013).
- Excessive glucagon-like peptide-1 exposure: Closely monitor for efficacy and assess for signs and symptoms of pancreatitis if therapy is initiated after surgery; gastric bypass and sleeve gastrectomy (but not gastric band) significantly increase endogenous postprandial GLP-1 concentrations (Korner 2009; Peterli 2012). Administration of exogenous GLP-1 agonists may be redundant to surgery effects.
• GI disease: Use is not recommended in patients with preexisting severe GI disease, including severe gastroparesis.
• Hepatic impairment: Use with caution in patients with hepatic impairment.
• Renal impairment: Use with caution in patients with renal impairment.
Other warnings/precautions:
• Appropriate use: Diabetes mellitus: Not recommended for first-line therapy in patients inadequately controlled on diet and exercise alone. Do not use in patients with type 1 diabetes mellitus or for the treatment of diabetic ketoacidosis; not a substitute for insulin.
None known.
Alpha-Lipoic Acid: May enhance the hypoglycemic effect of Antidiabetic Agents. Risk C: Monitor therapy
Androgens: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapy
Direct Acting Antiviral Agents (HCV): May enhance the hypoglycemic effect of Antidiabetic Agents. Risk C: Monitor therapy
Efgartigimod Alfa: May diminish the therapeutic effect of Fc Receptor-Binding Agents. Risk C: Monitor therapy
Guanethidine: May enhance the hypoglycemic effect of Antidiabetic Agents. Risk C: Monitor therapy
Hyperglycemia-Associated Agents: May diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapy
Hypoglycemia-Associated Agents: Antidiabetic Agents may enhance the hypoglycemic effect of Hypoglycemia-Associated Agents. Risk C: Monitor therapy
Insulins: Glucagon-Like Peptide-1 Agonists may enhance the hypoglycemic effect of Insulins. Management: Consider insulin dose reductions when used in combination with glucagon-like peptide-1 agonists. Risk D: Consider therapy modification
Liraglutide: May enhance the adverse/toxic effect of Glucagon-Like Peptide-1 Agonists. Risk X: Avoid combination
Maitake: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapy
Meglitinides: Glucagon-Like Peptide-1 Agonists may enhance the hypoglycemic effect of Meglitinides. Management: Consider meglitinide dose reductions when used in combination with glucagon-like peptide-1 agonists, particularly when also used with basal insulin. Risk D: Consider therapy modification
Monoamine Oxidase Inhibitors: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapy
Pegvisomant: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapy
Prothionamide: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapy
Quinolones: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Quinolones may diminish the therapeutic effect of Agents with Blood Glucose Lowering Effects. Specifically, if an agent is being used to treat diabetes, loss of blood sugar control may occur with quinolone use. Risk C: Monitor therapy
Ritodrine: May diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapy
Salicylates: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapy
Selective Serotonin Reuptake Inhibitors: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapy
Semaglutide: May enhance the adverse/toxic effect of Glucagon-Like Peptide-1 Agonists. Risk X: Avoid combination
Sincalide: Drugs that Affect Gallbladder Function may diminish the therapeutic effect of Sincalide. Management: Consider discontinuing drugs that may affect gallbladder motility prior to the use of sincalide to stimulate gallbladder contraction. Risk D: Consider therapy modification
Sulfonylureas: Glucagon-Like Peptide-1 Agonists may enhance the hypoglycemic effect of Sulfonylureas. Management: Consider sulfonylurea dose reductions when used in combination with glucagon-like peptide-1 agonists. Risk D: Consider therapy modification
Thiazide and Thiazide-Like Diuretics: May diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapy
Glucagon-like peptide-1 (GLP-1) receptor agonists are not recommended for patients with type 2 diabetes mellitus planning to become pregnant. Patients who could become pregnant should use effective contraception during therapy. Transition to a preferred therapy should be initiated prior to conception and contraception should be continued until glycemic control is achieved (ADA 2021; Alexopoulos 2019; Egan 2020)
Poorly controlled diabetes during pregnancy can be associated with an increased risk of adverse maternal and fetal outcomes, including diabetic ketoacidosis, preeclampsia, spontaneous abortion, preterm delivery, delivery complications, major malformations, stillbirth, and macrosomia (ACOG 201 2018). To prevent adverse outcomes, prior to conception and throughout pregnancy, maternal blood glucose and HbA1c should be kept as close to target goals as possible but without causing significant hypoglycemia (ADA 2021; Blumer 2013).
Agents other than dulaglutide are currently recommended to treat diabetes mellitus in pregnancy (ADA 2021).
It is not known if dulaglutide is present in breast milk. According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and benefits of treatment to the mother
Individualized medical nutrition therapy (MNT) based on ADA recommendations is an integral part of therapy.
Plasma glucose; renal function (in patients reporting severe GI reactions); signs/symptoms of pancreatitis; worsening diabetic retinopathy (in patients with a prior history).
HbA1c: Monitor at least twice yearly in patients who have stable glycemic control and are meeting treatment goals; monitor quarterly in patients in whom treatment goals have not been met, or with therapy change. Note: In patients prone to glycemic variability (eg, patients with insulin deficiency), or in patients whose HbA1c is discordant with serum glucose levels or symptoms, consider evaluating HbA1c in combination with blood glucose levels and/or a glucose management indicator (ADA 2021; KDIGO 2020).
Recommendations for glycemic control in patients with diabetes:
Nonpregnant adults (ADA 2021):
HbA1c: <7% (a more aggressive [<6.5%] or less aggressive [<8%] HbA1c goal may be targeted based on patient-specific characteristics). Note: In patients using a continuous glucose monitoring system, a goal of time in range >70% with time below range <4% is recommended and is similar to a goal HbA1c <7%.
Preprandial capillary blood glucose: 80 to 130 mg/dL (more or less stringent goals may be appropriate based on patient-specific characteristics).
Peak postprandial capillary blood glucose (~1 to 2 hours after a meal): <180 mg/dL (more or less stringent goals may be appropriate based on patient-specific characteristics).
Older adults (≥65 years of age) (ADA 2021):
Note: May consider less strict targets in patients who are using insulin and/or insulin secretagogues (sulfonylureas, meglitinides) (ES [LeRoith 2019]).
HbA1c: <7% to 7.5% (healthy); <8% to 8.5% (complex/intermediate health). Note: Individualization may be appropriate based on patient and caregiver preferences and/or presence of cognitive impairment. In patients with very complex or poor health (ie, limited remaining life expectancy), consider making therapy decisions based on avoidance of hypoglycemia and symptomatic hyperglycemia rather than HbA1c level.
Preprandial capillary blood glucose: 80 to 130 mg/dL (healthy); 90 to 150 mg/dL (complex/intermediate health); 100 to 180 mg/dL (very complex/poor health).
Bedtime capillary blood glucose: 80 to 180 mg/dL (healthy); 100 to 180 mg/dL (complex/intermediate health); 110 to 200 mg/dL (very complex/poor health).
Classification of hypoglycemia (ADA 2021):
Level 1: 54 to 70 mg/dL; hypoglycemia alert value; initiate fast-acting carbohydrate (eg, glucose) treatment.
Level 2: <54 mg/dL; threshold for neuroglycopenic symptoms; requires immediate action.
Level 3: Hypoglycemia associated with a severe event characterized by altered mental and/or physical status requiring assistance.
Dulaglutide is an agonist of human glucagon-like peptide-1 (GLP-1) receptor and augments glucose dependent insulin secretion and slows gastric emptying.
Bioavailability: 47% to 65%.
Distribution: Central volume, mean: 3.09 L; peripheral volume, mean: 5.98 L.
Metabolism: Degradation to amino acids by protein catabolism pathways.
Half-life elimination: ~5 days.
Time to peak, plasma: 24 to 72 hours.
Renal function impairment: Dulaglutide systemic exposure increased by 20%, 28%, 14%, and 12% for mild, moderate, and severe renal impairment, and ESRD, respectively.
Hepatic function impairment: Dulaglutide systemic exposure decreased by 23%, 33%, and 21% for mild, moderate, and severe hepatic impairment, respectively.
Solution Pen-injector (Trulicity Subcutaneous)
0.75 mg/0.5 mL (per 0.5 mL): $265.97
1.5 mg/0.5 mL (per 0.5 mL): $265.97
3 mg/0.5 mL (per 0.5 mL): $265.97
4.5 mg/0.5 mL (per 0.5 mL): $265.97
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