Dulaglutide (Trulicity)
Dulaglutide (LY2189265), a recombinant GLP-1 receptor agonist fused to a modified human IgG4 Fc fragment (PMID 25912221; FDA label 2025).
Dulaglutide is a once-weekly subcutaneous GLP-1 receptor agonist marketed as Trulicity, FDA-approved for glycemic control in adults and pediatric patients 10 years and older with type 2 diabetes, and to reduce the risk of major adverse cardiovascular events in adults with type 2 diabetes and established cardiovascular disease or multiple cardiovascular risk factors (FDA label 2025; PMID 33591618; PMID 31183384).
Last updated: 2026-03-10
Safety Summary
In a pooled analysis of 787 Chinese patients from AWARD-CHN1/CHN2, 28.6% reported at least one GI treatment-emergent adverse event (TEAE) by week 26. The most frequent were diarrhea (13.1%), nausea (6.6%), abdominal distension (6.4%), and vomiting (3.0%). Per FDA label, GI events were graded mild in approximately 48-58%, moderate in 35-42%, and severe in 7-11% of cases, with events peaking during the first 2 weeks and declining thereafter (PMID 32621083; FDA label 2025). Pancreatic amylase increased modestly within normal range (LS mean +5.7 U/L at 26 weeks) without associated pancreatitis events (PMID 34453682).
Known Side Effects
common
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rare
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Who Should NOT Use This
FDA boxed warning. GLP-1 receptor agonists caused thyroid C-cell tumors in rodents at clinically relevant exposures. Patients with personal or family history of MTC or MEN 2 must not use dulaglutide (FDA label 2025; PMID 25912221).
Serious hypersensitivity reactions including anaphylaxis and angioedema have been reported in the label (FDA label 2025).
Dulaglutide has not been studied in severe gastrointestinal disease and is not recommended in severe gastroparesis because it delays gastric emptying and can worsen GI intolerance. Patients with clinically significant gastric emptying abnormality were excluded from trials (FDA label 2025; PMID 34453682).
Patients with history of chronic or acute pancreatitis were excluded from AWARD trials. Acute pancreatitis has been reported; discontinue promptly if suspected (FDA label 2025; PMID 34453682).
Combination therapy increases hypoglycemia risk. The label recommends considering dose reduction of insulin secretagogues or insulin when used with dulaglutide (FDA label 2025; PMID 29430801; PMID 31758520).
Animal studies showed adverse fetal effects. The FDA label states dulaglutide should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Discontinue at least 2 months before planned pregnancy (FDA label 2025).
Cases of acute kidney injury and worsening of chronic renal failure have been reported postmarketing, sometimes in association with nausea, vomiting, diarrhea, or dehydration. Use caution in patients with renal impairment (FDA label 2025).
Cholelithiasis and cholecystitis have been reported in postmarketing data and the REWIND trial population. If cholelithiasis is suspected, gallbladder studies and clinical follow-up are indicated (FDA label 2025).
Talk to Your Doctor
Before considering Dulaglutide (Trulicity), discuss it with your healthcare provider. Ask about potential interactions with your current medications, whether it is appropriate for your health conditions, and what monitoring may be needed.
Sources: [1-21]
Evidence Assessment
Tier 1 -- FDA-approved biologic (September 2014) with extensive Phase 3 RCT data from the AWARD program (10+ trials, 5000+ patients). REWIND cardiovascular outcomes trial (n=9,901, median 5.4 years follow-up) demonstrated MACE reduction (PMID 33591618, PMID 31183384). Additional Phase 3 studies in Chinese and Japanese populations (PMID 32219675, PMID 31228090, PMID 30949907, PMID 31758520). Blood pressure meta-analysis from pooled AWARD data (PMID 36894938). Pancreatic safety data (PMID 34453682). GI safety pooled analysis (PMID 32621083). Biosimilar equivalence study (PMID 40214296). All source pack studies are published in peer-reviewed journals (FDA label 2025; PMID 24742660; PMID 25912221; PMID 32219675; PMID 33591618).
1Efficacy and safety of dulaglutide versus sitagliptin after 52 weeks in type 2 diabetes in a randomized controlled trial (AWARD-5)PMID 24742660
(2014) - Phase 3 RCT - N=1098 metformin-treated adults with type 2 diabetes
Dulaglutide 1.5 mg superior to sitagliptin for HbA1c change (-1.10% vs -0.39%), FPG, and body weight at 52 weeks.
2Safety and efficacy of once-weekly dulaglutide versus sitagliptin after 104 weeks in type 2 diabetes (AWARD-5 extension)PMID 25912221
(2015) - Phase 3 RCT extension - N=1098 (657 completed 104 weeks)
Sustained superiority over sitagliptin at 104 weeks. HbA1c -0.99% with 1.5 mg. HOMA2-%B improved. Molecule structure and DPP-4 resistance described.
3REWIND design and baseline characteristics of the cardiovascular outcome trial of dulaglutidePMID 31183384
(2019) - CVOT design/baseline - N=9,901
Large cardiovascular outcomes trial. 68.5% had no prior CV events. Mean HbA1c 7.3%, median follow-up 5.4 years.
4Dulaglutide and cardiovascular and renal outcomes in type 2 diabetes: REWIND analysisPMID 33591618
(2021) - CVOT post-hoc analysis - N=9,901
Dulaglutide reduced total burden of CV or fatal events. HR 0.88 (95% CI 0.79-0.99, p=0.026) for MACE over 5.4 years.
5Effects of dulaglutide on all-cause mortality in REWINDPMID 33239067
(2020) - CVOT analysis - N=9,901
Evaluated all-cause mortality outcomes in the REWIND population.
6Efficacy and Safety of Dulaglutide in Older Patients: A post hoc Analysis of the REWIND trialPMID 33537745
(2020) - CVOT post-hoc subgroup analysis - N=9,901 (5256 aged 65+, 4645 younger than 65)
Similar MACE reduction in patients 65+ vs younger. No increased safety risks in older adults. Similar efficacy and tolerability across age subgroups.
7Weight-dependent and weight-independent effects of dulaglutide on blood pressurePMID 36894938
(2023) - Pooled meta-analysis - Pooled from AWARD-1, 5, 8, 10
SBP -2.6 mmHg (36% weight-dependent, 64% weight-independent). Pulse pressure -2.5 mmHg (86% weight-independent).
8Pancreatic Safety of Once-Weekly Dulaglutide in Chinese Patients with Type 2 DiabetesPMID 34453682
(2021) - Phase 3 post-hoc safety analysis - N=203 Chinese patients
Modest pancreatic amylase increase (+5.7 U/L) within normal range. No pancreatitis signal. Not associated with baseline factors.
9Evaluation of Characteristics of Gastrointestinal Adverse Events with Once-Weekly DulaglutidePMID 32621083
(2020) - Phase 3 pooled GI safety analysis - N=787 Chinese patients
28.6% reported GI TEAEs by week 26. Diarrhea 13.1%, nausea 6.6%, abdominal distension 6.4%, vomiting 3.0%. Most mild to moderate, peaked first 2 weeks.
10Efficacy and safety of dulaglutide monotherapy compared with glimepiride in Chinese patients (AWARD-CHN1)PMID 32219675
(2020) - Phase 3 RCT - N=264 (OAM-naive Chinese patients; N=492 total study)
HbA1c -2.02% with 1.5 mg vs -1.37% glimepiride at 26 weeks. Weight -1.40 kg vs +0.73 kg.
11Efficacy and safety of dulaglutide versus insulin glargine in Chinese patients with type 2 diabetes (AWARD-CHN2)PMID 31228090
(2019) - Phase 3 RCT - N=607 Chinese patients
Dulaglutide non-inferior to insulin glargine for HbA1c reduction with weight loss advantage.
12Effect of the first administration of once-weekly dulaglutide on glucose levels in Japanese patients with type 2 diabetesPMID 30949907
(2019) - Pharmacodynamic crossover study - N=12 Japanese patients
Postprandial glucose AUC improved by week 1. CGM showed lower daily average glucose beginning the day after the first dose.
13Once-weekly dulaglutide with insulin therapy for type 2 diabetes: efficacy and safety in Japanese patientsPMID 31758520
(2020) - Phase 4 study - N=159 Japanese patients on insulin therapy
Dulaglutide 0.75 mg add-on to insulin improved HbA1c versus placebo in Japanese patients.
14Dulaglutide with insulin: subgroup analysis by insulin regimenPMID 31994009
(2020) - Phase 4 subgroup analysis - Japanese patients
Efficacy consistent across insulin regimen subgroups.
15Dulaglutide 1.5 mg as an add-on option for patients uncontrolled on insulinPMID 29430801
(2018) - Phase 3 RCT - N=445 on dulaglutide 1.5 mg + insulin
HbA1c -1.44% with dulaglutide vs -0.67% placebo. Effective across baseline HbA1c, age, and diabetes duration.
16Comprehensive review of dulaglutide clinical data (AWARD program overview)PMID 28606095
(2017) - Review - Review of AWARD Phase 3 program (5000+ patients)
Summarizes AWARD-1 through AWARD-10 results. Dulaglutide demonstrated consistent efficacy and tolerability.
17Patient-reported outcomes with dulaglutide in Japanese patients with type 2 diabetesPMID 27161178
(2016) - PRO analysis - Japanese patients
No deterioration in patient-reported outcomes with dulaglutide treatment.
18Effect of Orally Administered Semaglutide Versus Dulaglutide on Diabetes-Related Biomarkers (PIONEER 10)PMID 33460016
(2021) - Phase 3 RCT - N=458 (dulaglutide 0.75 mg, n=65)
Compared oral semaglutide to injectable dulaglutide 0.75 mg. Semaglutide showed greater HbA1c reduction at higher doses.
19Dulaglutide and Dapagliflozin Combination Concurrently Improves Endothelial Glycocalyx, Vascular, and Renal MarkersPMID 39768420
(2025) - RCT - N=60 (30 combination, 30 DPP-4i)
Combination improved PWV (-9.1%), endothelial glycocalyx (-8.1%), UACR (-52.3%), and GLS (18.19%) vs DPP-4i control.
20Efficacy and Safety of Dulaglutide Biosimilar (LY05008) in Chinese PatientsPMID 40214296
(2025) - Phase 3 biosimilar equivalence RCT - N=440 (222 LY05008, 218 dulaglutide)
LY05008 demonstrated pharmaceutical equivalence to dulaglutide. HbA1c LS mean difference within predefined margin. NMPA approved dulaglutide in China in 2019. 90% sequence homology confirmed.
21Efficacy and Safety of Once-Weekly Dulaglutide in Elderly Chinese Patients with Type 2 Diabetes: A Post Hoc Analysis of AWARD-CHN StudiesPMID 32857293
(2020) - Phase 3 post-hoc subgroup analysis - N=766 Chinese patients (222 aged 60+, 544 aged <60)
Similar HbA1c reduction in patients 60+ vs younger. Low incidence of hypoglycemia and GI TEAEs in both age groups.