Trulicity (Dulaglutide)


Indications

TRULICITY® is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.

1.1 Limitations of Use

  • TRULICITY is not recommended as a first-line therapy for patients who have inadequate glycemic control on diet and exercise because of the uncertain relevance of rodent C-cell tumor findings to humans. Prescribe TRULICITY only to patients for whom the potential benefits outweigh the potential risk
  • TRULICITY has not been studied in patients with a history of pancreatitis Consider other antidiabetic therapies in patients with a history of pancreatitis.
  • TRULICITY should not be used in patients with type 1 diabetes mellitus or for the treatment of diabetic ketoacidosis. TRULICITY is not a substitute for insulin.
  • TRULICITY has not been studied in patients with severe gastrointestinal disease, including severe gastroparesis. The use of TRULICITY is not recommended in patients with pre-existing severe gastrointestinal disease

contraindications

4.1 Medullary Thyroid Carcinoma

TRULICITY is contraindicated in patients with a personal or family history of medullary thyroid carcinoma (MTC) or in patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2).

4.2 Hypersensitivity

TRULICITY is contraindicated in patients with a prior serious hypersensitivity reaction to dulaglutide or to any of the product components

adverse reactions

The following serious reactions are described below or elsewhere in the prescribing information:

  • Risk of Thyroid C-cell Tumors
  • Pancreatitis
  • Hypoglycemia with Concomitant Use of Insulin Secretagogues or Insulin
  • Hypersensitivity reactions
  • Renal impairment
  • Severe Gastrointestinal Disease

6.1 Clinical Studies Experience

Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in practice.

Pool of Placebo-controlled Trials

The data in Table 1 are derived from the placebo-controlled trials.

These data reflect exposure of 1670 patients to TRULICITY and a mean duration of exposure to TRULICITY of 23.8 weeks. Across the treatment arms, the mean age of patients was 56 years, 1% were 75 years or older and 53% were male. The population in these studies was 69% White, 7% Black or African American, 13% Asian; 30% were of Hispanic or Latino ethnicity. At baseline, the population had diabetes for an average of 8.0 years and had a mean HbA1c of 8.0%. At baseline, 2.5% of the population reported retinopathy. Baseline estimated renal function was normal or mildly impaired (eGFR ≥60mL/min/1.73 m2) in 96.0% of the pooled study populations.

Table 1 shows common adverse reactions, excluding hypoglycemia, associated with the use of TRULICITY in the pool of placebo-controlled trials. These adverse reactions were not present at baseline, occurred more commonly on TRULICITY than on placebo, and occurred in at least 5% of patients treated with TRULICITY.

Table 1: Adverse Reactions in Placebo-Controlled Trials Reported in ≥5% of TRULICITY-Treated Patients

a Includes diarrhea, fecal volume increased, frequent bowel movements.

b Includes retching, vomiting, vomiting projectile.

c Includes abdominal discomfort, abdominal pain, abdominal pain lower, abdominal pain upper, abdominal tenderness, gastrointestinal pain.

d Includes fatigue, asthenia, malaise.

  Note: Percentages reflect the number of patients that reported at least 1 treatment-emergent occurrence of the adverse reaction.

Adverse Reaction Placebo
(N=568)
%
TRULICITY 0.75 mg
(N=836)
%
TRULICITY 1.5 mg
(N=834)
%
Nausea 5.3 12.4 21.1
Diarrheaa 6.7 8.9 12.6
Vomitingb 2.3 6.0 12.7
Abdominal Painc 4.9 6.5 9.4
Decreased Appetite 1.6 4.9 8.6
Dyspepsia 2.3 4.1 5.8
Fatigued 2.6 4.2 5.6

In the pool of placebo-controlled trials, gastrointestinal adverse reactions occurred more frequently among patients receiving TRULICITY than placebo (placebo 21.3%, 0.75 mg 31.6%, 1.5 mg 41.0%). More patients receiving TRULICITY 0.75 mg (1.3%) and TRULICITY 1.5 mg (3.5%) discontinued treatment due to gastrointestinal adverse reactions than patients receiving placebo (0.2%). Investigators graded the severity of gastrointestinal adverse reactions occurring on 0.75 mg and 1.5 mg of TRULICITY as “mild” in 58% and 48% of cases, respectively, “moderate” in 35% and 42% of cases, respectively, or “severe” in 7% and 11% of cases, respectively.

In addition to the reactions in Table 1, the following adverse reactions were reported more frequently in TRULICITY-treated patients than placebo (frequencies listed, respectively, as: placebo; 0.75 mg; 1.5 mg): constipation (0.7%, 3.9%, 3.7%), flatulence (1.4%, 1.4%, 3.4%), abdominal distension (0.7%, 2.9%, 2.3%), gastroesophageal reflux disease (0.5%, 1.7%, 2.0%), and eructation (0.2%, 0.6%, 1.6%).

Pool of Placebo- and Active-Controlled Trials

The occurrence of adverse reactions was also evaluated in a larger pool of patients with type 2 diabetes participating in 6 placebo- and active-controlled trials evaluating the use of TRULICITY as monotherapy and add-on therapy to oral medications or insulin.[see Clinical Studies (14)]. In this pool, a total of 3342 patients with type 2 diabetes were treated with TRULICITY for a mean duration of 52 weeks. The mean age of patients was 56 years, 2% were 75 years or older and 51% were male. The population in these studies was 71% White, 7% Black or African American, 11% Asian; 32% were of Hispanic or Latino ethnicity. At baseline, the population had diabetes for an average of 8.2 years and had a mean HbA1c of 7.6-8.5%. At baseline, 5.2% of the population reported retinopathy. Baseline estimated renal function was normal or mildly impaired (eGFR ≥60 ml/min/1.73 m2) in 95.7% of the TRULICITY population.

In the pool of placebo- and active-controlled trials, the types and frequency of common adverse reactions, excluding hypoglycemia, were similar to those listed in Table 1.

Other Adverse Reactions

Table 2 summarizes the incidence of documented symptomatic (≤70 mg/dL glucose threshold) and severe hypoglycemia in the placebo-controlled clinical studies.

Table 2: Incidence (%) of Documented Symptomatic and Severe Hypoglycemia Adverse Reactions in Placebo-Controlled Trials
Placebo TRULICITY 0.75 mg TRULICITY 1.5 mg
Add-on to Metformin
      (26 weeks) N=177 N=302 N=304
      Documented symptomatic 1.1% 2.6% 5.6%
      Severe 0 0 0
Add-on to Metformin + Pioglitazone
(26 weeks) N=141 N=280 N=279
      Documented symptomatic 1.4% 4.6% 5.0%
      Severe 0 0 0
Add-on to Glimepiride
      (24 weeks) N=60 N=239
      Documented symptomatic 1.7% 11.3%
      Severe 0 0
In Combination with Insulin Glargine ± Metformin
      (28 weeks) N=150 N=150
      Documented symptomatic 30.0% 35.3%
      Severe 0 0.7%

Hypoglycemia was more frequent when TRULICITY was used in combination with a sulfonylurea or insulin In a 78-week clinical trial, documented symptomatic hypoglycemia occurred in 39% and 40% of patients when TRULICITY 0.75 mg and 1.5 mg, respectively, was co-administered with a sulfonylurea. Severe hypoglycemia occurred in 0% and 0.7% of patients when TRULICITY 0.75 mg and 1.5 mg, respectively, was co-administered with a sulfonylurea. Documented symptomatic hypoglycemia occurred in 85% and 80% of patients when TRULICITY 0.75 mg and 1.5 mg, respectively, was co-administered with prandial insulin. Severe hypoglycemia occurred in 2.4% and 3.4% of patients when TRULICITY 0.75 mg and 1.5 mg, respectively, was co-administered with prandial insulin.

TRULICITY 0.75 mg and 1.5 mg resulted in a mean increase in heart rate (HR) of 2-4 beats per minute (bpm). The long-term clinical effects of the increase in HR have not been established.

Adverse reactions of sinus tachycardia were reported more frequently in patients exposed to TRULICITY. Sinus tachycardia was reported in 3.0%, 2.8%, and 5.6% of patient treated with placebo, TRULICITY 0.75 mg and TRULICITY 1.5 mg, respectively. Persistence of sinus tachycardia (reported at more than 2 visits) was reported in 0.2%, 0.4% and 1.6% of patients treated with placebo, TRULICITY 0.75 mg and TRULICITY 1.5 mg, respectively. Episodes of sinus tachycardia, associated with a concomitant increase from baseline in heart rate of ≥15 beats per minute, were reported in 0.7%, 1.3% and 2.2% of patient treated with placebo, TRULICITY 0.75 mg and TRULICITY 1.5 mg, respectively.

Across four Phase 2 and five Phase 3 clinical studies, 64 (1.6%) TRULICITY-treated patients developed anti-drug antibodies (ADAs) to the active ingredient in TRULICITY (i.e., dulaglutide).

Of the 64 dulaglutide-treated patients that developed dulaglutide ADAs, 34 patients (0.9% of the overall population) had dulaglutide-neutralizing antibodies, and 36 patients (0.9% of the overall population) developed antibodies against native GLP-1.

The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, the incidence of antibodies to dulaglutide cannot be directly compared with the incidence of antibodies of other products.

Systemic hypersensitivity adverse reactions sometimes severe (e.g., severe urticaria, systemic rash, facial edema, lip swelling) occurred in 0.5% of patients on TRULICITY in the four Phase 2 and five Phase 3 studies.

In the placebo-controlled studies, injection-site reactions (e.g., injection-site rash, erythema) were reported in 0.5% of TRULICITY-treated patients and in 0.0% of placebo-treated patients.

A mean increase from baseline in PR interval of 2-3 milliseconds was observed in TRULICITY-treated patients in contrast to a mean decrease of 0.9 milliseconds in placebo-treated patients. The adverse reaction of first degree AV block occurred more frequently in patients treated with TRULICITY than placebo (0.9%, 1.7% and 2.3% for placebo, TRULICITY 0.75 mg and TRULICITY 1.5 mg, respectively). On electrocardiograms, a PR interval increase to at least 220 milliseconds was observed in 0.7%, 2.5% and 3.2% of patients treated with placebo, TRULICITY 0.75 mg and TRULICITY 1.5 mg, respectively.

Patients exposed to TRULICITY had mean increases from baseline in lipase and/or pancreatic amylase of 14% to 20%, while placebo-treated patients had mean increases of up to 3%.

6.2 Postmarketing Experience

The following additional adverse reactions have been reported during post-approval use of TRULICITY. Because these events are reported voluntarily from a population of uncertain size, it is generally not possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

  • Anaphylactic reactions.

warnings and precautions

5.1 Risk of Thyroid C-cell Tumors

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. Glucagon-like peptide (GLP-1) receptor agonists have induced thyroid C-cell adenomas and carcinomas in mice and rats at clinically relevant exposures. It is unknown whether TRULICITY will cause 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.

One case of MTC was reported in a patient treated with TRULICITY. This patient had pretreatment calcitonin levels approximately 8 times the upper limit of normal (ULN). Cases of MTC in patients treated with liraglutide, another GLP-1 receptor agonist, have been reported in the postmarketing period; the data in these reports are insufficient to establish or exclude a causal relationship between MTC and GLP-1 receptor agonist use in humans.

TRULICITY is contraindicated in patients with a personal or family history of MTC or in patients with MEN 2. Counsel patients regarding the potential risk for MTC with the use of TRULICITY and inform them of symptoms of thyroid tumors (e.g. a 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 treated with TRULICITY. Such monitoring may increase the risk of unnecessary procedures, due to the low test specificity for serum calcitonin and a high background incidence of thyroid disease. Significantly elevated serum calcitonin value may indicate MTC and patients with MTC usually have calcitonin values >50 ng/L. If serum calcitonin is measured and found to be elevated, the patient should be further evaluated. Patients with thyroid nodules noted on physical examination or neck imaging should also be further evaluated.

5.2 Pancreatitis

In Phase 2 and Phase 3 clinical studies, 12 (3.4 cases per 1000 patient years) pancreatitis-related adverse reactions were reported in patients exposed to TRULICITY versus 3 in non-incretin comparators (2.7 cases per 1000 patient years). An analysis of adjudicated events revealed 5 cases of confirmed pancreatitis in patients exposed to TRULICITY (1.4 cases per 1000 patient years) versus 1 case in non-incretin comparators (0.88 cases per 1000 patient years).

After initiation of TRULICITY, observe patients carefully for signs and symptoms of pancreatitis, including persistent severe abdominal pain. If pancreatitis is suspected, promptly discontinue TRULICITY. If pancreatitis is confirmed, TRULICITY should not be restarted. TRULICITY has not been evaluated in patients with a prior history of pancreatitis. Consider other antidiabetic therapies in patients with a history of pancreatitis.

5.3 Hypoglycemia with Concomitant Use of Insulin Secretagogues or Insulin

The risk of hypoglycemia is increased when TRULICITY is used in combination with insulin secretagogues (e.g., sulfonylureas) or insulin. Patients may require a lower dose of sulfonylurea or insulin to reduce the risk of hypoglycemia in this setting.

5.4 Hypersensitivity Reactions

There have been postmarketing reports of serious hypersensitivity reactions (e.g., anaphylactic reactions and angioedema) in patients treated with TRULICITY If a hypersensitivity reaction occurs, the patient should discontinue TRULICITY and other suspected medications and promptly seek medical advice. Anaphylaxis and angioedema have been 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 because it is unknown whether such patients will be predisposed to anaphylaxis with TRULICITY.

5.5 Renal Impairment

In patients treated with GLP-1 receptor agonists, there have been postmarketing reports of acute renal failure and worsening of chronic renal failure, which may sometimes require hemodialysis. Some of these events were reported in patients without known underlying renal disease. A majority of reported events occurred in patients who had experienced nausea, vomiting, diarrhea, or dehydration. Because these reactions may worsen renal function, use caution when initiating or escalating doses of TRULICITY in patients with renal impairment. Monitor renal function in patients with renal impairment reporting severe adverse gastrointestinal reactions

5.6 Severe Gastrointestinal Disease

Use of TRULICITY may be associated with gastrointestinal adverse reactions, sometimes severe. TRULICITY has not been studied in patients with severe gastrointestinal disease, including severe gastroparesis, and is therefore not recommended in these patients.

5.7 Macrovascular Outcomes

There have been no clinical studies establishing conclusive evidence of macrovascular risk reduction with TRULICITY.

general medication guide

This Medication Guide has been approved by the U.S. Food and Drug Administration.


TRU-0003-MG-20170127

Revised: January 2017

Medication Guide
TRULICITY® (Trū-li-si-tee) (dulaglutide)
injection, for subcutaneous use
Read this Medication Guide before you start using TRULICITY and each time you get a refill. There may be new information. This information does not take the place of talking to your healthcare provider about your medical condition or your treatment.

What is the most important information I should know about TRULICITY?

TRULICITY may cause serious side effects, including:

  • Possible thyroid tumors, including cancer. Tell your healthcare provider if you get a lump or swelling in your neck, hoarseness, trouble swallowing, or shortness of breath. These may be symptoms of thyroid cancer. In studies with rats or mice, TRULICITY and medicines that work like TRULICITY caused thyroid tumors, including thyroid cancer. It is not known if TRULICITY will cause thyroid tumors or a type of thyroid cancer called medullary thyroid carcinoma (MTC) in people.
  • Do not use TRULICITY if you or any of your family have ever had a type of thyroid cancer called medullary thyroid carcinoma (MTC), or if you have an endocrine system condition called Multiple Endocrine Neoplasia syndrome type 2 (MEN 2).
What is TRULICITY?
TRULICITY is an injectable prescription medicine that may improve blood sugar (glucose) in adults with type 2 diabetes mellitus, and should be used along with diet and exercise.
  • TRULICITY is not recommended as the first choice of medicine for treating diabetes.
  • It is not known if TRULICITY can be used in people who have had pancreatitis.
  • TRULICITY is not a substitute for insulin and is not for use in people with type 1 diabetes or people with diabetic ketoacidosis.
  • TRULICITY is not recommended for use in people with severe stomach or intestinal problems.
  • It is not known if TRULICITY is safe and effective for use in children under 18 years of age.
Do not use TRULICITY if:
  • You or any of your family have ever had a type of thyroid cancer called medullary thyroid carcinoma (MTC) or if you have an endocrine system condition called Multiple Endocrine Neoplasia syndrome type 2 (MEN 2).
  • You are allergic to dulaglutide or any of the ingredients in TRULICITY. See the end of this Medication Guide for a complete list of ingredients in TRULICITY.
Before using TRULICITY, tell your healthcare provider if you have any medical conditions including:
  • Have or have had problems with your pancreas, kidneys or liver.
  • Have severe problems with your stomach, such as slowed emptying of your stomach (gastroparesis) or problems with digesting food.
  • Are pregnant or plan to become pregnant. It is not known if TRULICITY will harm your unborn baby. Tell your healthcare provider if you become pregnant while using TRULICITY.
  • Are breastfeeding or plan to breastfeed. It is not known if TRULICITY passes into your breast milk. You and your healthcare provider should decide if you should breastfeed while taking TRULICITY.
Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. TRULICITY may affect the way some medicines work and some medicines may affect the way TRULICITY works.
Before using TRULICITY, talk to your healthcare provider about low blood sugar and how to manage it. Tell your healthcare provider if you are taking other medicines to treat diabetes including insulin or sulfonylureas.
Know the medicines you take. Keep a list of them to show your healthcare provider and pharmacist when you get a new medicine.
How should I use TRULICITY?
  • Read the Instructions for Use that comes with TRULICITY.
  • Use TRULICITY exactly as your healthcare provider tells you to.
  • Your healthcare provider should show you how to use TRULICITY before you use it for the first time.
  • TRULICITY is injected under the skin (subcutaneously) of your stomach (abdomen), thigh, or upper arm. Do not inject TRULICITY into a muscle (intramuscularly) or vein (intravenously).
  • Use TRULICITY 1 time each week on the same day each week at any time of the day.
  • You may change the day of the week as long as your last dose was given 3 or more days before.
  • If you miss a dose of TRULICITY, take the missed dose as soon as possible if there are at least 3 days (72 hours) until your next scheduled dose. If there are less than 3 days remaining, skip the missed dose and take your next dose on the regularly scheduled day. Do not take 2 doses of TRULICITY within 3 days of each other.
  • TRULICITY may be taken with or without food.
  • Do not mix insulin and TRULICITY together in the same injection.
  • You may give an injection of TRULICITY and insulin in the same body area (such as, your stomach area), but not right next to each other.
  • Change (rotate) your injection site with each weekly injection. Do not use the same site for each injection.
  • Do not share your TRULICITY pen, syringe, or needles with another person. You may give another person an infection or get an infection from them.
Your dose of TRULICITY and other diabetes medicines may need to change because of:
  • Change in level of physical activity or exercise, weight gain or loss, increased stress, illness, change in diet, or because of other medicines you take.
What are the possible side effects of TRULICITY?
TRULICITY may cause serious side effects, including:
  • See “What is the most important information I should know about TRULICITY?”
  • Inflammation of your pancreas (pancreatitis). Stop using TRULICITY and call your healthcare provider right away if you have severe pain in your stomach area (abdomen) that will not go away, with or without vomiting. You may feel the pain from your abdomen to your back.
  • Low blood sugar (hypoglycemia). Your risk for getting low blood sugar may be higher if you use TRULICITY with another medicine that can cause low blood sugar, such as a sulfonylurea or insulin.
Signs and symptoms of low blood sugar may include:
  • Dizziness or light-headedness
  • Sweating
  • Confusion or drowsiness
  • Headache
  • Blurred vision
  • Slurred speech
  • Shakiness
  • Fast heartbeat
  • Anxiety, irritability, or mood changes
  • Hunger
  • Weakness
  • Feeling jittery
  • Serious allergic reactions. Stop using TRULICITY and get medical help right away, if you have any symptoms of a serious allergic reaction including itching, rash, or difficulty breathing.
  • Kidney problems (kidney failure). In people who have kidney problems, diarrhea, nausea, and vomiting may cause a loss of fluids (dehydration) which may cause kidney problems to get worse.
  • Severe stomach problems. Other medicines like TRULICITY may cause severe stomach problems. It is not known if TRULICITY causes or worsens stomach problems.
The most common side effects of TRULICITY may include nausea, diarrhea, vomiting, decreased appetite, indigestion.
Talk to your healthcare provider about any side effect that bothers you or does not go away. These are not all the possible side effects of TRULICITY.
Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
General information about the safe and effective use of TRULICITY.
Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use TRULICITY for a condition for which it was not prescribed. Do not give TRULICITY to other people, even if they have the same symptoms you have. It may harm them.
This Medication Guide summarizes the most important information about TRULICITY. If you would like more information, talk with your healthcare provider. You can ask your pharmacist or healthcare provider for information about TRULICITY that is written for health professionals.
What are the ingredients in TRULICITY?
Active ingredient: dulaglutide
Inactive ingredients: citric acid anhydrous, mannitol, polysorbate 80, and trisodium citrate dihydrate
TRULICITY is a registered trademark of Eli Lilly and Company.
Manufactured by: Eli Lilly and Company, Indianapolis, IN 46285, USA, US License Number 1891
www.TRULICITY.com.
For more information go to www.TRULICITY.com or call 1-800-545-5979.
Copyright © 2014, 2017 Eli Lilly and Company. All rights reserved.

overdosage

Overdoses have been reported in clinical studies. Effects associated with these overdoses were primarily mild or moderate gastrointestinal events (e.g., nausea, vomiting) and non-severe hypoglycemia. In the event of overdose, appropriate supportive care (including frequent plasma glucose monitoring) should be initiated according to the patient’s clinical signs and symptoms.

description

TRULICITY contains dulaglutide, a human GLP-1 receptor agonist. The molecule is a fusion protein that consists of 2 identical, disulfide-linked chains, each containing an N-terminal GLP-1 analog sequence covalently linked to the Fc portion of a modified human immunoglobulin G4 (IgG4) heavy chain by a small peptide linker and is produced using mammalian cell culture. The GLP-1 analog portion of dulaglutide is 90% homologous to native human GLP-1 (7-37). Structural modifications were introduced in the GLP-1 part of the molecule responsible for interaction with the enzyme dipeptidyl-peptidase-IV (DPP-4). Additional modifications were made in an area with a potential T-cell epitope and in the areas of the IgG4 Fc part of the molecule responsible for binding the high-affinity Fc receptors and half-antibody formation. The overall molecular weight of dulaglutide is approximately 63 kilodaltons.

TRULICITY is a clear, colorless, sterile solution. Each 0.5 mL of TRULICITY solution contains 0.75 mg or 1.5 mg of dulaglutide. Each single-dose pen or prefilled syringe contains 0.5 mL of solution and the following excipients: citric acid anhydrous (0.07 mg), mannitol (23.2 mg), polysorbate 80 (0.10 mg), trisodium citrate dihydrate (1.37 mg), in water for injection.

Trulicity Package Photos

About the Author

Truman Lewis
Truman has been a bureau chief and correspondent in D.C., Los Angeles, Phoenix and elsewhere, reporting for radio, television, print and news services, for more than 30 years. Most recently, he has reported extensively on health and consumer issues for ConsumerAffairs.com and FairfaxNews.com.