What Is Dulaglutide?
Dulaglutide is a medication that acts as a long-acting glucagon-like peptide-1 (GLP-1) receptor agonist. This means it mimics the action of a natural hormone in the body that helps regulate blood sugar levels. By activating GLP-1 receptors, dulaglutide helps the body release insulin when blood sugar is high, reduces the amount of sugar produced by the liver, and slows down digestion, which can contribute to a feeling of fullness. It is also described as having properties similar to a natural satiety hormone.
Dulaglutide is widely studied for the treatment of type 2 diabetes mellitus. Clinical trials are also investigating its potential role in managing conditions such as obesity and nonalcoholic fatty liver disease (NAFLD), including its more severe form, nonalcoholic steatohepatitis (NASH).
Research on dulaglutide began with the first trial on July 15, 2011. To date, 89 trials involving dulaglutide have been conducted or are ongoing, with a total enrollment of over 1.1 million participants. Most of these trials, 63, have been completed, while 6 are currently recruiting new participants.
Uses and Conditions Under Study
Dulaglutide is primarily studied for its effects on type 2 diabetes and related metabolic disorders. The majority of research, spanning 69 trials, focuses on various forms of type 2 diabetes mellitus. As a GLP-1 receptor agonist, dulaglutide helps improve blood sugar control in these patients by stimulating insulin release, reducing glucose production, and slowing gastric emptying.
Beyond diabetes, dulaglutide is also being investigated for its potential in managing weight. There are 6 trials specifically examining dulaglutide in individuals with obesity and those who are overweight. GLP-1 analogues are known to contribute to weight loss and act as natural satiety hormones, making them a subject of interest for weight management strategies.
Another significant area of study for dulaglutide involves nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH). These liver conditions are common in patients with type 2 diabetes, and research suggests that GLP-1 analogues may help improve liver enzyme levels and potentially address the progression of these diseases. Several trials are exploring these benefits.
Additionally, dulaglutide has been studied in 5 trials involving healthy volunteers. These studies typically assess the drug's pharmacokinetics (how the body absorbs, distributes, metabolizes, and excretes the drug) and overall safety profile in individuals without the target condition.
Other areas of interest mentioned in trial summaries include its potential role in intracranial large artery atherosclerotic disease (ICAD), type 1 diabetes with poor glycemic control, and endocrine complications in β-thalassemia patients, though these conditions are not listed as primary trial conditions with multiple studies.
Dosing
Dulaglutide is administered as a subcutaneous injection, meaning it is injected under the skin. It is typically given once weekly, as indicated in several study descriptions.
Various strengths of dulaglutide have been investigated in clinical trials for different purposes. Common doses include 0.75 milligrams (mg) and 1.5 mg, which have been studied in both healthy participants and those with type 2 diabetes mellitus to understand their effects and safety profiles. Higher doses such as 3 mg and 4.5 mg have also been explored, often in trials seeking to optimize glycemic control or weight management outcomes. A 0.5 mg dose has also been part of some investigations.
The drug is available in pre-filled pens or administered via manual syringes, facilitating its once-weekly injection. Some studies also evaluate dulaglutide in combination with other agents, such as SGLT2 inhibitors and finerenone, or with different insulin regimens, to assess the benefits of multi-drug therapies for complex conditions like type 2 diabetes and its associated complications.
Side Effects
Nausea was the most commonly reported side effect, affecting 15.3% of patients taking Dulaglutide, compared to 5.5% of patients on placebo across 16 trials involving 7463 patients. Diarrhea was also common, experienced by 13.2% of patients on Dulaglutide versus 8.4% on placebo in 15 trials with 7451 patients. Other frequent side effects observed in patients taking Dulaglutide (also known as Trulicity) included:
- Decreased appetite: 8.3% of patients reported this, compared to 2.2% on placebo (12 trials, 6727 patients).
- Vomiting: 7.8% of patients experienced vomiting, compared to 3.3% on placebo (12 trials, 6917 patients).
- Hypoglycaemia (low blood sugar): 8.4% of patients experienced this, compared to 7.2% on placebo (1 trial, 4943 patients).
- Constipation: 7.3% of patients experienced constipation, compared to 4.1% on placebo (9 trials, 6501 patients).
- Headache: 6.4% of patients reported headache, compared to 5.7% on placebo (11 trials, 6986 patients).
Some events, such as nasopharyngitis (10.4% on Dulaglutide vs 10.4% on placebo) and back pain (8.0% on Dulaglutide vs 8.0% on placebo), occurred at similar rates in both the Dulaglutide and placebo groups.
Clinical Trial Results
Cardiovascular Outcomes (NCT01394952)
The REWIND trial evaluated the cardiovascular effects of Dulaglutide in 4949 patients receiving Dulaglutide and 4952 patients receiving placebo. Key findings related to cardiovascular health included:
- A composite outcome of cardiovascular death, non-fatal myocardial infarction (heart attack), or non-fatal stroke occurred in 12.0% (594 patients) of those on Dulaglutide, compared to 13.4% (663 patients) on placebo.
- All-cause mortality was observed in 10.8% (536 patients) of the Dulaglutide group, versus 11.9% (592 patients) in the placebo group.
- A composite microvascular endpoint occurred in 22.2% (1099 patients) of patients on Dulaglutide, compared to 25.1% (1241 patients) on placebo.
- Hospitalization for unstable angina occurred in 1.8% (88 patients) of the Dulaglutide group, compared to 1.6% (77 patients) in the placebo group.
Drug Interactions: Warfarin (NCT01432938)
A study in healthy participants examined the effect of Dulaglutide on the blood-thinning medication Warfarin. When Dulaglutide was given with Warfarin, the overall exposure to Warfarin components (R-warfarin and S-warfarin) remained similar to Warfarin alone. However, the time to reach maximum concentration (Tmax) for Warfarin was delayed (e.g., 8.00 hours for R-warfarin with Dulaglutide vs 2.00 hours for Warfarin alone), and the maximum concentration (Cmax) of Warfarin was slightly lower.
Drug Interactions: Digoxin (NCT01436201)
In a study of healthy participants, Dulaglutide's effect on the heart medication Digoxin was assessed. The overall exposure to Digoxin (AUC) was similar whether taken with or without Dulaglutide. However, the maximum concentration (Cmax) of Digoxin was lower when taken with Dulaglutide (e.g., 1.34 ng/mL vs 1.71 ng/mL), and the time to reach maximum concentration (Tmax) was delayed (1.50 hours with Dulaglutide vs 1.00 hour without).
Drug Interactions: Oral Contraceptives (NCT01458210)
A study in healthy female participants investigated the interaction between Dulaglutide and oral contraceptives (Ortho-Cyclen, containing Ethinyl Estradiol and Norelgestromin). When taken with Dulaglutide, the maximum concentrations (Cmax) of both Ethinyl Estradiol and Norelgestromin were lower, and their time to maximum concentration (Tmax) was delayed. For Norelgestromin, overall exposure (AUC) was also slightly lower with Dulaglutide, while Ethinyl Estradiol exposure remained similar.
Dulaglutide Delivery Method (NCT01524770)
A study comparing the delivery of Dulaglutide via an auto-injector versus a manual syringe in healthy participants found that both methods resulted in similar overall drug exposure (AUC), maximum concentrations (Cmax), and time to maximum concentration (Tmax). For example, the time to maximum concentration was 48.0 hours for both the auto-injector and manual syringe.
Currently Recruiting Trials
Researchers are actively studying Dulaglutide in a variety of clinical trials to explore its potential benefits for different conditions. These studies aim to understand how Dulaglutide works and if it can help patients beyond its current uses.
- One study, NCT07282041, is a Phase 2/Phase 3 trial sponsored by the National University of Singapore. It is investigating the role of Dulaglutide in patients with severe intracranial atherosclerosis and ischemic stroke. The study aims to enroll 130 participants to evaluate if Dulaglutide can improve endothelial function, a key mechanism in these conditions.
- Another trial, NCT07319286, is a Phase 1/Phase 2 study from Ain Shams University. This research focuses on adolescent females with Type 1 diabetes mellitus who experience menstrual irregularities. It seeks to enroll 50 participants to assess the therapeutic effect of Dulaglutide on these irregularities.
- A Phase 2 study, NCT07109700, sponsored by Hangzhou Zhongmei Huadong Pharmaceutical Co., Ltd., is comparing an investigational drug, HDM1005, against Dulaglutide. This trial is for participants with Type 2 Diabetes not adequately controlled by diet, exercise, or metformin, with an enrollment target of 216 individuals.
- Eli Lilly and Company is sponsoring NCT06739122, a Phase 3 trial called AWARD-PEDS PLUS. This study is evaluating additional dosing options for Dulaglutide in pediatric participants with Type 2 Diabetes, planning to include 55 children.
- The University of Hong Kong is conducting NCT06324461, a Phase 4 study to determine if a GLP-1 Receptor Agonist can reduce myocardial injury after non-cardiac surgery. This trial is recruiting 372 patients undergoing elective non-cardiac surgery.
- Finally, NCT04731272, a Phase 2 study from the University of Pennsylvania, is exploring GLP-1 Agonist therapy in individuals with cystic fibrosis-related glucose intolerance. It aims to enroll 30 participants with pancreatic insufficient cystic fibrosis and abnormal glucose tolerance.
Where to Participate
Clinical trials for Dulaglutide are conducted across a broad geographic range, making participation accessible to many. Currently, studies are active at 42 sites in 38 cities across 26 states.
Some of the top locations for these trials include:
- Philadelphia, Pennsylvania (3 sites)
- Houston, Texas (2 sites)
- Los Angeles, California (2 sites)
- Washington D.C., District of Columbia (2 sites)
- Denver, Colorado (1 site)
- New Haven, Connecticut (1 site)
- Jacksonville, Florida (1 site)
- Miami, Florida (1 site)
- Orlando, Florida (1 site)
- Tamarac, Florida (1 site)
Eligibility for these trials generally includes participants aged 10 to 80 years, of all genders. Healthy volunteers are typically not included, but children are eligible for certain studies.
Development Timeline
The journey of Dulaglutide in clinical development began on July 15, 2011, with the earliest trials. Since then, a robust research program has unfolded, encompassing a total of 89 trials and involving over 1,135,695 participants.
Eli Lilly and Company has been a primary driver of this research, sponsoring 36 trials. Initial investigations explored conditions such as IBS-C and hyperphosphatemia. Over time, the scope of research expanded significantly, with a strong focus on Type 2 Diabetes Mellitus, which became a central indication.
The development pipeline broadened to include a diverse range of conditions, from general diabetes and obesity to more specific areas like cardiovascular risk, diabetic kidney disease, and even novel applications such as intracranial atherosclerosis and menstrual irregularities. The majority of studies have progressed to later stages, with 23 trials reaching Phase 3 and 19 trials in Phase 4, indicating a mature and comprehensive development program. The latest trial is projected to conclude on April 17, 2026, demonstrating ongoing commitment to exploring the full potential of Dulaglutide.