In adult patients with type 2 diabetes:
With the addition of the CV indication, Trulicity is proven to do more1
Trulicity has proven MACE-3 risk reduction* in both primary and secondary prevention† patients1
CV = cardiovascular
*Trulicity 1.5 mg reduced the risk of MACE-3 (CV death, nonfatal MI, or nonfatal stroke) by 12% in patients without established CVD who have multiple CV risk factors and patients with established CVD.2
†Primary prevention: Reducing the risk of atherosclerotic cardiovascular disease (ASCVD) by preventing or managing risk factors. Secondary prevention: Reducing the risk of another event in people who have had a serious CV incident or procedure.3
A GLP-1 RA CVOT designed differently than any other2,4-10
REWIND is the only GLP-1 RA CVOT to include a majority of patients without established CVD*
A chart compares GLP-1 RA Cardiovascular Outcomes Trials.
Trulicity’s REWIND2,4 study had 9901 patients, 31% of them had prior cardiovascular disease, 46% of them were female, and the median follow-up was 5.4 years.
Bydureon’s EXSCEL5 study had 14752 patients, 73% of them had prior cardiovascular disease, 38% of them were female, and the median follow-up was 3.8 years.
Victoza’s LEADER6 study had 9340 patients, 81% of them had prior cardiovascular disease, 36% of them were female, and the median follow-up was 3.8 years.
Ozempic’s SUSTAIN-67 study had 3297 patients, 83% of them had prior cardiovascular disease, 39% of them were female, and the median follow-up was 2.1 years.
Rybelsus’ PIONEER 68,9 study had 3183 patients, 85% of them had prior cardiovascular disease, 32% of them were female, and the median follow-up was 1.3 years.
Adlyxin’s ELIXA10 study had 6068 patients, 100% of them had prior cardiovascular disease, 31% of them were female, and the median follow-up was 2.1 years.
Criteria for prior cardiovascular disease may vary between study protocols. Please refer to study descriptions for individual study criteria.
No comparison can be made between GLP-1 RA CVOT outcomes due to differences in study design, population, and key inclusion/exclusion criteria.
*In REWIND, patients without established CV disease had multiple CV risk factors.
†In a study that evaluated the generalizability of the results of GLP-1 RA CVOTs to the overall population of type 2 diabetes patients in the US, key baseline characteristics of four GLP-1 RA CVOTs (EXSCEL, LEADER, REWIND, and SUSTAIN-6) were compared to the characteristics in a reference of the general type 2 diabetes population (primarily from IQVIA database). Based on its criteria, 42.6% of the reference population were eligible for enrollment in REWIND, versus 15.9% in EXSCEL, 13.0% in SUSTAIN-6, and 12.9% in LEADER. None of the trials were fully representative of the reference population, which included commercially insured patients <65 years of age, but may not be aligned to the general population.9
CVOT=cardiovascular outcomes trial; GLP-1 RA=glucagon-like peptide-1 receptor agonist; CVD=cardiovascular disease;
CV=cardiovascular; MI=myocardial infarction
Select Important Safety Information:
Pancreatitis has been reported in clinical trials. Observe patients for signs and symptoms including persistent severe abdominal pain sometimes radiating to the back, which may or may not be accompanied by vomiting. If pancreatitis is suspected, discontinue Trulicity promptly. Do not restart if pancreatitis is confirmed. Consider other antidiabetic therapies in patients with a history of pancreatitis.
Trulicity is the first and only GLP-1 RA to reduce the risk of CV death, nonfatal MI, or nonfatal stroke* in both primary and secondary prevention† patients1
*Trulicity 1.5 mg reduced the risk of MACE-3 (CV death, nonfatal MI, or nonfatal stroke) by 12% in patients without established CVD who have multiple CV risk factors and patients with established CVD.2
†Primary prevention: Reducing the risk of atherosclerotic cardiovascular disease (ASCVD) by preventing or managing risk factors. Secondary prevention: Reducing the risk of another event in people who have had a serious CV incident or procedure.3
CV indications for GLP-1 RAs‡
A chart compares the cardiovascular (CV) indications of oral or injectable GLP-1 RAs that are marketed in the US, have a cardiovascular outcomes trial (CVOT), and are indicated for risk reduction of major adverse cardiovascular events, which include CV death, nonfatal myocardial infarction (MI), and nonfatal stroke for patients with type 2 diabetes.
The five medications in the chart are given a checkmark showing if they are indicated for primary prevention patients with multiple CV risk factors or for secondary prevention patients with established cardiovascular disease (CVD).
Trulicity1 is shown to be indicated for both primary prevention patients with multiple CV risk factors and for secondary prevention patients with established CVD.
Rybelsus11 is shown to be indicated for neither primary prevention patients with multiple CV risk factors nor for secondary prevention patients with established CVD.
Ozempic12 is shown to be indicated for secondary prevention patients with established CVD but not primary prevention patients with multiple CV risk factors.
Victoza13 is shown to be indicated for secondary prevention patients with established CVD but not primary prevention patients with multiple CV risk factors.
Bydureon14 is shown to be indicated for neither primary prevention patients with multiple CV risk factors nor for secondary prevention patients with established CVD.
‡Indicated for risk reduction of major adverse CV events (CV death, nonfatal MI, or nonfatal stroke) for patients with type 2 diabetes.
MI=myocardial infarction
This chart includes oral or injectable GLP-1 RAs that are marketed in the US and have a CVOT.
Trulicity showed a significant reduction of MACE-3,* even with a majority primary prevention patient population†2
Median follow-up was 5.4 years with the Kaplan-Meier curves starting to diverge within the first year.
Trulicity is indicated to reduce the risk of major adverse CV events (cardiovascular death, nonfatal myocardial infarction, nonfatal stroke) in adults with type 2 diabetes mellitus.1
- Without established CVD who have multiple CV risk factors
- With established CVD
The primary composite outcome (MACE-3) occurred in 594 (12.0%) participants assigned to Trulicity + standard of care and 663 (13.4%) participants assigned to placebo + standard of care (hazard ratio [HR] 0.88, 95% confidence interval [CI] 0.79-0.99; P=.026).
The safety profile of Trulicity was consistent with the GLP-1 receptor agonist class.2 The most common adverse events leading to the discontinuation of Trulicity were gastrointestinal events.15
*MACE-3 is a composite outcome comprising CV death, nonfatal MI, or nonfatal stroke.†Primary prevention: Reducing the risk of ASCVD by preventing or managing risk factors.
Secondary prevention: Reducing the risk of another event in people who have had a serious CV incident or procedure.3
In the Trulicity CVOT, risk reduction was seen even with a relatively well-controlled mean baseline A1C for patients with type 2 diabetes2,4
REWIND participants had lower baseline A1C levels compared to other GLP-1 RA CVOTs 2,4-8,10,16
Mean Baseline A1C
No comparison can be made between GLP-1 RA CVOT outcomes due to differences in study design, population, and key inclusion/exclusion criteria.
A chart displays patients’ mean baseline A1C levels within different GLP-1 RAs cardiovascular outcome trials.
Trulicity’s REWIND2,4 study participants had a mean baseline A1C of 7.3%.
Bydureon’s EXSCEL5 study participants had a mean baseline A1C of 8.0% (median).
Victoza’s LEADER6 study participants had a mean baseline A1C of 8.7%.
Ozempic’s SUSTAIN-67 study participants had a mean baseline A1C of 8.7%.
Rybelsus’ PIONEER 68,9 study participants had a mean baseline A1C of 8.2%.
Adlyxin’s ELIXA10 study participants had a mean baseline A1C of 7.7%.
Trulicity CVOT study description2,4
REWIND was a global, randomized, double-blind, placebo-controlled, event-driven study
Trulicity’s cardiovascular outcomes trial (CVOT), REWIND, was a global, randomized, double-blind, placebo-controlled, event-driven study. It was designed to include patients1 with type 2 diabetes who are at least 50 years old, have an A1C less than or equal to 9.5%, have cardiovascular disease (CVD) or cardiovascular risk factors, and have been on no more than 2 oral antidiabetic drugs with or without basal insulin for 3 months or longer.
The primary objective was to determine whether treatment with Trulicity (1.5 milligrams once a week) has a lower hazard of cardiovascular events compared with placebo in patients receiving standard of care.
The primary outcome was MACE-3 (composite of CV death, nonfatal myocardial infarction, or nonfatal stroke).
*Criteria listed do not encompass the full inclusion/exclusion criteria of the trial. See the REWIND study description for a more complete representation.
- Gerstein HC, Colhoun HM, Dagenais GR, et al. Design and baseline characteristics of participants in the Researching cardiovascular Events with a Weekly INcretin in Diabetes (REWIND) trial on the cardiovascular effects of dulaglutide. Diabetes Obes Metab. 2018;20(1):42‐49.
REWIND did not include patients with a coronary or cerebrovascular event within 2 months prior to randomization or plans to revascularize, and an eGFR<15 mL/min/1.73m2 or on dialysis.
CV=cardiovascular; CVD=cardiovascular disease; OADs=oral antidiabetic drugs; MACE-3=major adverse cardiovascular events; MI=myocardial infarction
REWIND study description2,4
- Multicenter, randomized, double-blind, placebo-controlled, event-driven trial designed to assess whether once-weekly Trulicity 1.5 mg safely reduces the incidence of cardiovascular (CV) outcomes compared to placebo in adult patients with type 2 diabetes with and without CVD
- Key inclusion criteria: Established or newly detected type 2 diabetes with an A1C ≤9.5%; stable dose of up to 2 oral glucose-lowering drugs with or without basal insulin; BMI ≥23 kg/m2; age ≥50 years with established clinical vascular disease*, OR age ≥55 years and subclinical† vascular disease, OR age ≥60 years and at least 2 or more CV risk factors‡
- Key exclusion criteria: Uncontrolled diabetes; severe hypoglycemia in preceding year; coronary or cerebrovascular event in preceding 2 months; plans to revascularize; estimated glomerular filtration rate (eGFR) <15 mL/min/1.73 m2; on dialysis; gastric bypass or emptying abnormality; prior pancreatitis; liver disease; family or personal history of C-cell hyperplasia, medullary thyroid cancer, multiple endocrine neoplasia (MEN) 2A or 2B, or calcitonin ≥20 pg/mL; unwilling to stop GLP-1 RA, dipeptidyl peptidase-4 (DPP-4) inhibitor, or weight loss drug; cancer within preceding 5 years; possible pregnancy; life expectancy <1 year
- 9901 patients were randomized to receive Trulicity 1.5 mg or same volume of placebo in addition to standard of care treatments such as oral antidiabetic treatments, insulin, and antihypertensive, antiplatelet, and lipid-lowering therapies; patients were assessed every 6 months until 1200 confirmed primary outcomes had accrued
- Primary outcome was the first occurrence of the composite of either nonfatal MI, nonfatal stroke, or CV death (MACE-3). All outcomes occurring on or after randomization were included in analysis; Kaplan-Meier estimates were used to generate cumulative risks and Cox proportional hazard models were used to determine the effect of intervention on the outcome and to estimate HR and 95% CIs
Study results2
The primary composite outcome, major adverse cardiovascular events (MACE-3), occurred in 594 (12.0%) participants assigned to Trulicity and 663 (13.4%) participants assigned to placebo (hazard ratio [HR] 0.88, 95% confidence interval [CI] 0.79-0.99; P=.026).
Study Groups2,4
Placebo (n=4952)
Trulicity 1.5 mg QW, SC (n=4949)
*History of myocardial infarction (MI), ischemic stroke, revascularization, hospitalization for unstable angina with concordant new ischemic electrocardiogram changes, or a positive stress test with concordant imaging.4
†Myocardial ischemia, coronary, carotid, or lower extremity artery stenosis exceeding 50%, ankle to brachial index <0.9, hypertension with left ventricular hypertrophy, eGFR <60 mL/min per 1.73m2, or albuminuria.4
‡Tobacco use, dyslipidemia, hypertension, or abdominal obesity.2
Therapies at baseline
Most REWIND participants were taking various CV and antidiabetic medications at the beginning of the study2
CV therapies at baseline
Antidiabetic medications at baseline
ACE=angiotensin-converting enzyme; ARB=angiotensin-receptor blocker
Study Descriptions
REWIND2,4
- Multicenter, randomized, double-blind, placebo-controlled, event-driven trial designed to assess whether once-weekly Trulicity 1.5 mg safely reduces the incidence of cardiovascular (CV) outcomes compared to placebo in adult patients with type 2 diabetes with and without CVD
- Key inclusion criteria: Established or newly detected type 2 diabetes with an A1C ≤9.5%; stable dose of up to 2 oral glucose-lowering drugs with or without basal insulin; BMI ≥23 kg/m2; age ≥50 years with established clinical vascular disease*, OR age ≥55 years and subclinical† vascular disease, OR age ≥60 years and at least 2 or more CV risk factors‡
- Key exclusion criteria: Uncontrolled diabetes; severe hypoglycemia in preceding year; coronary or cerebrovascular event in preceding 2 months; plans to revascularize; estimated glomerular filtration rate (eGFR) <15 mL/min/1.73 m2; on dialysis; gastric bypass or emptying abnormality; prior pancreatitis; liver disease; family or personal history of C-cell hyperplasia, medullary thyroid cancer, multiple endocrine neoplasia (MEN) 2A or 2B, or calcitonin ≥20 pg/mL; unwilling to stop GLP-1 RA, dipeptidyl peptidase-4 (DPP-4) inhibitor, or weight loss drug; cancer within preceding 5 years; possible pregnancy; life expectancy <1 year
- 9901 patients were randomized to receive Trulicity 1.5 mg or same volume of placebo in addition to standard of care treatments such as oral antidiabetic treatments, insulin, and antihypertensive, antiplatelet, and lipid-lowering therapies; patients were assessed every 6 months until 1200 confirmed primary outcomes had accrued
- Primary outcome was the first occurrence of the composite of either nonfatal MI, nonfatal stroke, or CV death (MACE-3). All outcomes occurring on or after randomization were included in analysis; Kaplan-Meier estimates were used to generate cumulative risks and Cox proportional hazard models were used to determine the effect of intervention on the outcome and to estimate HR and 95% CIs
*History of myocardial infarction (MI), ischemic stroke, revascularization, hospitalization for unstable angina with concordant new ischemic electrocardiogram changes, or a positive stress test with concordant imaging.4
†Myocardial ischemia, coronary, carotid, or lower extremity artery stenosis exceeding 50%, ankle to brachial index <0.9, hypertension with left ventricular hypertrophy, eGFR <60 mL/min per 1.73m2, or albuminuria.4
‡Tobacco use, dyslipidemia, hypertension, or abdominal obesity.2
EXSCEL5
- Pragmatic, randomized, double-blind, placebo-controlled, parallel-group, event-driven trial to assess the long-term cardiovascular safety and efficacy of Bydureon in patients with type 2 diabetes
- Key inclusion criteria: ≥18 years of age with an A1C ≥6.5% to ≤10.0%; had been treated with ≤3 oral antihyperglycemic agents or insulin, alone or in combination with ≤2 oral antihyperglycemic agents; designed to have approximately 70% of patients with previous cardiovascular events defined as at least one of the following: history of major clinical manifestation of coronary artery disease (myocardial infarction, coronary revascularization, or coronary angiography showing at least one stenosis ≥50%); ischemic cerebrovascular disease (history of ischemic stroke or history of carotid disease with ≥50% stenosis); or atherosclerotic peripheral arterial disease (amputation, ankle to brachial index or toe to brachial index <0.9, or history of revascularization)
- 14752 patients were randomized to receive either Bydureon 2 mg (QW, SC) or matched placebo, in addition to standard of care
- Primary composite outcome was the first occurrence of nonfatal myocardial infarction, nonfatal stroke, or CV death
LEADER6
- Multicenter, randomized, double-blind, placebo-controlled, time- and event-driven trial to assess the long-term effects of Victoza on CV outcomes and other clinically important events in patients with type 2 diabetes
- Key inclusion criteria: Patients with type 2 diabetes with an A1C ≥7.0%, not previously treated with drugs for type 2 diabetes or had been treated with one or more antihyperglycemic agents with or without insulin, ≥50 years of age with at least one CV condition (coronary heart disease, cerebrovascular disease, peripheral vascular disease, chronic kidney disease of stage ≥3, or chronic heart failure [New York Heart Association class II or III]), ≥60 years of age with at least one CV risk factor (microalbuminuria or proteinuria, hypertension and left ventricular hypertrophy, left ventricular systolic or diastolic dysfunction, or an ankle to brachial index <0.9)
- 9340 patients were randomized to receive either Victoza 1.8 mg (or maximum tolerated dose QD, SC) or matched placebo, in addition to standard of care
- Primary composite outcome was the first occurrence of nonfatal myocardial infarction, nonfatal stroke, or CV death
SUSTAIN-67
- Randomized, double-blind, placebo-controlled, parallel-group, event-driven trial to assess the noninferiority of Ozempic as compared to placebo in terms of cardiovascular safety in patients with type 2 diabetes
- Key inclusion criteria: Type 2 diabetes and an A1C ≥7.0%; not previously treated for type 2 diabetes with an antihyperglycemic drug or had been treated with ≤2 oral antihyperglycemic agents with or without basal or premixed insulin; ≥50 years of age with established cardiovascular disease (previous cardiovascular, cerebrovascular, or peripheral vascular disease), chronic heart failure (New York Heart Association class II or III), or chronic kidney disease stage ≥3; ≥60 years of age with at least one CV risk factor (microalbuminuria or proteinuria, hypertension and left ventricular hypertrophy, left ventricular systolic or diastolic dysfunction, or an ankle to brachial index <0.9)
- 3297 patients were randomized to receive either Ozempic 0.5 mg or 1.0 mg (QW, SC) or volume-matched placebo, in addition to standard of care
- Primary composite outcome was the first occurrence of nonfatal myocardial infarction, nonfatal stroke, or CV death
PIONEER-68,9
- Randomized, double-blind, placebo-controlled, event-driven trial to assess the cardiovascular safety of Rybelsus in patients with type 2 diabetes
- Key inclusion criteria: Patients with type 2 diabetes, age ≥50 years with established CVD (prior myocardial infarction; prior stroke or transient ischemic attack; prior coronary, carotid or peripheral arterial revascularization; >50% stenosis of coronary, carotid, or lower extremity arteries; documented history of symptomatic coronary heart disease; documented asymptomatic cardiac ischemia or chronic heart failure [New York Heart Association class II or III]) or moderate (stage 3) chronic kidney disease; age ≥60 years with at least one cardiovascular risk factor (microalbuminuria or proteinuria, hypertension and left ventricular hypertrophy, left ventricular systolic or diastolic dysfunction, or ankle to brachial index <0.9)
- 3183 patients were randomized to receive either Rybelsus (target dose of 14 mg QD, PO) or placebo, in addition to standard of care
- Primary composite outcome was the first occurrence of nonfatal myocardial infarction, nonfatal stroke, or CV death
ELIXA10
- Multicenter, randomized, double-blind, placebo-controlled, event-driven trial to assess the effect of Adlyxin on cardiovascular outcomes in patients with type 2 diabetes who had had a recent acute coronary syndrome, defined as an ST-segment elevation myocardial infarction (STEMI), non-STEMI, or unstable angina
- Key inclusion criteria: Patients with type 2 diabetes who had had an acute coronary event ≤180 days prior to screening
- Key exclusion criteria: Age less than 30 years, A1C less than 5.5% or greater than 11%
- 6068 patients were randomized to receive either Adlyxin 10-20ug (QD, SC) or placebo, in addition to standard of care
- Primary composite outcome was the first occurrence of nonfatal myocardial infarction, nonfatal stroke, CV death or hospitalization for unstable angina
Indications and Limitations of Use
Trulicity1
Indication: Trulicity (dulaglutide) is indicated:
- as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.
- to reduce the risk of major adverse cardiovascular events (cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke) in adults with type 2 diabetes mellitus who have established cardiovascular disease or multiple cardiovascular risk factors.
Limitations of Use
- Has not been studied in patients with a history of pancreatitis. Consider other antidiabetic therapies in these patients.
- Not for the treatment of type 1 diabetes mellitus.
- Has not been studied in patients with severe gastrointestinal disease, including severe gastroparesis and is therefore not recommended in these patients.
Rybelsus11
Indication: Rybelsus is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.
Limitations of Use
- Rybelsus 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.
- Rybelsus has not been studied in patients with a history of pancreatitis. Consider other antidiabetic therapies in patients with a history of pancreatitis.
- Rybelsus is not indicated for use in patients with type 1 diabetes mellitus or for the treatment of patients with diabetic ketoacidosis, as it would not be effective in these settings.
Ozempic12
Indication: Ozempic is indicated:
- as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.
- to reduce the risk of major adverse cardiovascular events (cardiovascular death, nonfatal myocardial infarction or nonfatal stroke) in adults with type 2 diabetes mellitus and established cardiovascular disease.
Limitations of Use
- Ozempic has not been studied in patients with a history of pancreatitis. Consider other antidiabetic therapies in patients with a history of pancreatitis.
- Ozempic is not a substitute for insulin. Ozempic is not indicated for use in patients with type 1 diabetes mellitus or for the treatment of patients with diabetic ketoacidosis, as it would not be effective in these settings.
Victoza13
Indication: Victoza is indicated:
- as an adjunct to diet and exercise to improve glycemic control in patients 10 years and older with type 2 diabetes mellitus,
- to reduce the risk of major adverse cardiovascular events (cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke) in adults with type 2 diabetes mellitus and established cardiovascular disease.
Limitations of Use
- Victoza should not be used in patients with type 1 diabetes mellitus or for the treatment of diabetic ketoacidosis, as it would not be effective in these settings.
- The concurrent use of Victoza and prandial insulin has not been studied.
Bydureon14
Indication: Bydureon is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.
Limitations of Use
- Bydureon is not recommended as first-line therapy for patients who have inadequate glycemic control on diet and exercise because of the uncertain relevance of the rat thyroid C-cell tumor findings to humans.
- Bydureon is not a substitute for insulin. Bydureon is not indicated for use in patients with type 1 diabetes mellitus or for the treatment of diabetic ketoacidosis, as it would not be effective in these settings.
- The concurrent use of Bydureon with prandial insulin has not been studied.
- Bydureon is an extended-release formulation of exenatide. Bydureon should not be used with other products containing the active ingredient exenatide.
- Bydureon has not been studied in patients with a history of pancreatitis. Consider other antidiabetic therapies in patients with a history of pancreatitis.
References
- Trulicity [Prescribing Information]. Indianapolis, IN: Lilly USA, LLC.
- Gerstein HC, Colhoun HM, Dagenais GR, et al. Dulaglutide and cardiovascular outcomes in type 2 diabetes (REWIND): a double‐blind, randomised placebo‐controlled trial. Lancet. 2019;394(10193):121‐130.
- Grundy SM, Stone NJ, Bailey AL, et al. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 2019;139(25):e1082-e1143.
- Gerstein HC, Colhoun HM, Dagenais GR, et al. Design and baseline characteristics of participants in the Researching cardiovascular Events with a Weekly INcretin in Diabetes (REWIND) trial on the cardiovascular effects of dulaglutide. Diabetes Obes Metab. 2018;20(1):42‐49.
-
Holman RR, Bethel MA, Mentz RJ, et al. Effects of once‐weekly exenatide on cardiovascular outcomes in type 2 diabetes.
N Engl J Med. 2017;377(13):1228‐1239. - Marso SP, Daniels GH, Brown‐Frandsen K, et al. Liraglutide and cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2016;375(4):311‐322.
- Marso SP, Bain SC, Consoli A, et al. Semaglutide and cardiovascular outcomes in patients with type 2 diabetes. N Engl J Med. 2016;375(19):1834‐1844.
- Husain M, Birkenfeld AL, Donsmark M, et al. Oral semaglutide and cardiovascular outcomes in patients with type 2 diabetes. N Engl J Med. 2019;381(9):841‐851.
- Bain SC, Mosenzon O, Arechavaleta R, et al. Cardiovascular safety of oral semaglutide in patients with type2 diabetes: rationale, design and patient baseline characteristics for the PIONEER 6 trial. Diabetes Obes Metab. 2019;21(3):499‐508.
- Pfeffer MA, Claggett B, Diaz R, et al. Lixisenatide in patients with type 2 diabetes and acute coronary syndrome. N Engl J Med. 2015;373(23):2247‐2257.
- Rybelsus [Prescribing Information]. Bagsvaerd, Denmark: Novo Nordisk A/S.
- Ozempic [Prescribing Information]. Bagsvaerd, Denmark: Novo Nordisk A/S.
- Victoza [Prescribing Information]. Bagsvaerd, Denmark: Novo Nordisk A/S.
- Bydureon [Prescribing Information]. Wilmington, DE: AstraZeneca Pharmaceuticals LP.
- Data on file, Lilly USA, LLC. DOF-DG-US-0105.
- Bentley‐Lewis R, Aguilar D, Riddle MC, et al. Rationale, design, and baseline characteristics in Evaluation of LIXisenatide in Acute Coronary Syndrome, a long‐term cardiovascular end point trial of lixisenatide versus placebo. Am Heart J. 2015;169(5):631‐638.
INDICATION
Trulicity (dulaglutide) is indicated
- as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.
- to reduce the risk of major adverse cardiovascular events (cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke) in adults with type 2 diabetes mellitus who have established cardiovascular disease or multiple cardiovascular risk factors.
LIMITATIONS OF USE:
- Has not been studied in patients with a history of pancreatitis. Consider other antidiabetic therapies in these patients.
- Not for the treatment of type 1 diabetes mellitus.
- Has not been studied in patients with severe gastrointestinal disease, including severe gastroparesis and is therefore not recommended in these patients.
IMPORTANT SAFETY INFORMATION
WARNING: 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. It is unknown whether Trulicity 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.
Trulicity 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 Trulicity 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 is of uncertain value for early detection of MTC in patients treated with Trulicity.
Trulicity is contraindicated in patients with a personal or family history of MTC or in patients with MEN 2, and in patients with a serious hypersensitivity reaction to dulaglutide or any of the product components.
Risk of Thyroid C-cell Tumors: One case of MTC was reported in a patient treated with Trulicity in a clinical study. This patient had pretreatment calcitonin levels approximately 8 times the upper limit of normal (ULN). An additional case of C-cell hyperplasia with elevated calcitonin levels following treatment was reported in the cardiovascular outcomes trial (REWIND). If serum calcitonin is measured and found to be elevated or thyroid nodules are noted on physical examination or neck imaging, the patient should be further evaluated.
Pancreatitis: Has been reported in clinical trials. Observe patients for signs and symptoms including persistent severe abdominal pain sometimes radiating to the back, which may or may not be accompanied by vomiting. If pancreatitis is suspected, discontinue Trulicity promptly. Do not restart if pancreatitis is confirmed. Consider other antidiabetic therapies in patients with a history of pancreatitis.
Hypoglycemia: Patients receiving Trulicity in combination with an insulin secretagogue (e.g., sulfonylurea) or insulin may have an increased risk of hypoglycemia, including severe hypoglycemia. The risk of hypoglycemia may be lowered by a reduction in the dose of sulfonylurea (or other concomitantly administered insulin secretagogue) or insulin. Inform patients using these concomitant medications of the risk of hypoglycemia and educate them on the signs and symptoms of hypoglycemia.
Hypersensitivity Reactions: There have been postmarketing reports of serious hypersensitivity reactions (eg, anaphylactic reactions and angioedema) in patients treated with Trulicity. Instruct patients who experience symptoms to discontinue Trulicity and promptly seek medical advice. Use caution in a patient with a history of angioedema or anaphylaxis with another GLP-1 receptor agonist as it is unknown whether they will be predisposed to anaphylaxis with Trulicity.
Acute Kidney Injury: In patients treated with GLP-1 RAs, there have been postmarketing reports of acute renal failure and worsening of chronic renal failure, sometimes requiring hemodialysis. A majority of reported events occurred in patients who had experienced nausea, vomiting, diarrhea, or dehydration. In patients with renal impairment, use caution when initiating or escalating doses of Trulicity and monitor renal function in patients experiencing severe adverse gastrointestinal reactions.
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.
Diabetic Retinopathy Complications: Have been reported in a cardiovascular outcomes trial. Monitor patients with a history of diabetic retinopathy.
Acute Gallbladder Disease: Acute events of gallbladder disease such as cholelithiasis or cholecystitis have been reported in GLP-1 receptor agonist trials and postmarketing. In a cardiovascular outcomes trial with a median follow up of 5.4 years, cholelithiasis occurred at a rate of 0.62/100 patient-years in Trulicity-treated patients and 0.56/100 patient-years in placebo-treated patients after adjusting for prior cholecystectomy. Serious events of acute cholecystitis were reported in 0.5% and 0.3% of patients on Trulicity and placebo respectively. If cholelithiasis is suspected, gallbladder studies and appropriate clinical follow-up are indicated.
The most common adverse reactions reported in ≥5% of Trulicity-treated patients in trials were nausea, diarrhea, vomiting, abdominal pain, decreased appetite, dyspepsia, and fatigue.
Gastric emptying: Trulicity slows gastric emptying, which may impact absorption of concomitantly administered oral medications. Use caution when oral medications are used with Trulicity. Drug levels of oral medications with a narrow therapeutic index should be adequately monitored when concomitantly administered with Trulicity. In clinical pharmacology studies, Trulicity did not affect the absorption of the tested, orally administered medications to a clinically relevant degree.
Pregnancy: Limited data with Trulicity in pregnant women are not sufficient to determine a drug-associated risk for major birth defects and miscarriage. Based on animal reproduction studies, there may be risks to the fetus from exposure to dulaglutide. Use only if potential benefit justifies the potential risk to the fetus.
Lactation: There are no data on the presence of dulaglutide in human milk, the effects on the breastfed infant, or the effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for Trulicity and any potential adverse effects on the breastfed infant from Trulicity or from the underlying maternal condition.
Pediatric Use: Safety and effectiveness of Trulicity have not been established and use is not recommended in patients less than 18 years of age.
Please click to access Prescribing Information, including Boxed Warning about possible thyroid tumors including thyroid cancer, and Medication Guide.
Please see Instructions for Use included with the pen.
DG HCP ISI 10JUN2022