Trulicity (Dulaglutide) Safety Signals and FDA Actions: What Patients and Clinicians Need to Know

What is the main FDA safety signal for Trulicity?

Trulicity is a once-weekly subcutaneous GLP-1 receptor agonist approved as a biologic in September 2014 (BLA 125469) [1]. The current prescribing information is effective June 16, 2026 (version 62), and the severe gastrointestinal adverse reactions section was updated in March 2026 [1]. Its most prominent safety signal is the boxed warning for thyroid C-cell tumors.

In male and female rats, dulaglutide caused a dose-related and treatment-duration-dependent increase in thyroid C-cell tumors, including adenomas and carcinomas, after lifetime exposure [1]. The label states that human relevance has not been determined and that it is unknown whether Trulicity causes thyroid C-cell tumors, including medullary thyroid carcinoma, in humans [1]. Trulicity is contraindicated in patients with a personal or family history of medullary thyroid carcinoma or with multiple endocrine neoplasia syndrome type 2 [1]. The label advises counseling about the potential risk and symptoms of thyroid tumors, such as a mass in the neck, dysphagia, dyspnea or persistent hoarseness [1]. Routine serum calcitonin monitoring or thyroid ultrasound is of uncertain value for early detection, according to the label [1].

What other warnings are on the Trulicity label?

The Warnings and Precautions section lists acute pancreatitis; hypoglycemia when used with insulin or an insulin secretagogue; hypersensitivity reactions; acute kidney injury due to volume depletion; severe gastrointestinal adverse reactions, with a statement that Trulicity is not recommended in patients with severe gastroparesis; diabetic retinopathy complications in patients with a history of diabetic retinopathy; acute gallbladder disease; and pulmonary aspiration during general anesthesia or deep sedation [1].

The label gives specific monitoring instructions. It says to monitor renal function in patients reporting adverse reactions that could lead to volume depletion, especially during initiation and dose escalation [1]. It says to monitor patients with a history of diabetic retinopathy [1]. It also says to instruct patients to inform healthcare providers of planned surgeries or procedures because of the aspiration risk [1].

What did REWIND show about cardiovascular outcomes?

REWIND was a double-blind, placebo-controlled trial in 9,901 adults aged 50 or older with type 2 diabetes and either established cardiovascular disease or cardiovascular risk factors; 31.5% had established cardiovascular disease [2]. Participants received dulaglutide 1.5 mg weekly or placebo and were followed for a median of 5.4 years [2]. The primary composite of non-fatal myocardial infarction, non-fatal stroke or cardiovascular death occurred in 12.0% of the dulaglutide group versus 13.4% of the placebo group (hazard ratio 0.88, 95% CI 0.79-0.99; p=0.026) [2]. All-cause death occurred in 10.8% versus 12.0% (HR 0.90, not significant) [2]. The label separately reports fatal or non-fatal stroke in 3.2% versus 4.1% (HR 0.76) [1].

What did REWIND show about kidney outcomes?

An exploratory analysis of REWIND examined a renal composite of new macroalbuminuria, a sustained decline in eGFR of 30% or more, or chronic renal replacement therapy [3]. The composite occurred in 17.1% of dulaglutide patients (3.5 per 100 person-years) and 19.6% of placebo patients (4.1 per 100 person-years) [3]. The label's indications are glycemic control and cardiovascular risk reduction, not kidney protection [1].

Separately, the label warns about acute kidney injury due to volume depletion, with most reported events occurring in patients who had gastrointestinal reactions such as nausea, vomiting or diarrhea leading to dehydration [1]. Some postmarketing cases required hemodialysis [1].

How common are gastrointestinal side effects?

In the adult placebo-controlled pool, nausea occurred in 5.3% of placebo patients, 12.4% of patients on 0.75 mg and 21.1% of patients on 1.5 mg [1]. Diarrhea occurred in 6.7%, 8.9% and 12.6%, and vomiting in 2.3%, 6.0% and 12.7%, respectively [1]. Any gastrointestinal adverse reaction occurred in 21%, 32% and 41% [1]. Treatment was stopped for gastrointestinal reasons in 0.2%, 1.3% and 3.5% [1]. Severe gastrointestinal adverse reactions were reported in 1.4% on placebo, 2.2% on 0.75 mg and 4.3% on 1.5 mg [1].

In the AWARD-11 trial of 1,842 adults on metformin, adverse reaction rates through 36 weeks were nausea in 13.4% with 1.5 mg, 15.6% with 3 mg and 16.4% with 4.5 mg; diarrhea in 7.0%, 11.4% and 10.7%; and vomiting in 5.6%, 8.3% and 9.3% [4].

What about hypoglycemia?

The label says that combining Trulicity with insulin or an insulin secretagogue can increase the risk of hypoglycemia, including severe hypoglycemia, and that reducing the dose of the insulin secretagogue or insulin may be necessary [1]. In the label's placebo-controlled table, glucose below 54 mg/dL occurred in 14.7% of patients adding Trulicity 1.5 mg to insulin glargine versus 9.3% on placebo plus glargine [1]. With glimepiride, the rate was 3.3% on Trulicity 1.5 mg versus 0% on placebo [1].

What does the label say about pancreatitis and gallbladder disease?

The label lists acute pancreatitis, including fatal and non-fatal hemorrhagic or necrotizing pancreatitis, as a warning for GLP-1 receptor agonists including Trulicity [1]. It says to observe patients for signs and symptoms such as persistent or severe abdominal pain, sometimes radiating to the back, with or without nausea or vomiting, and to discontinue Trulicity if pancreatitis is suspected [1].

For gallbladder disease, the label lists acute gallbladder disease as a warning and says that gallbladder studies are indicated if cholelithiasis or cholecystitis are suspected [1].

What postmarketing reactions are in the label?

The label describes postmarketing reports of serious hypersensitivity reactions, including anaphylactic reactions and angioedema [1]. If a hypersensitivity reaction occurs, the label says to discontinue Trulicity, treat promptly per standard of care and monitor until signs and symptoms resolve [1]. It also describes postmarketing reports of acute kidney injury, covered above [1].