Dulaglutide solved the once-weekly problem a different way from semaglutide. Instead of a fatty acid that binds albumin, two GLP-1 analogue chains are fused to a modified antibody Fc fragment, which is large enough to circulate for about a week. It is a large protein, filed as a biologic (a BLA rather than an NDA), and it comes in a single-use pen with a hidden needle that made it the easiest injection in the class for years.
Mechanism and receptor profile
The Trulicity label describes dulaglutide as a human GLP-1 receptor agonist with 90% amino-acid sequence homology to endogenous human GLP-1(7-37). It activates the GLP-1 receptor on pancreatic beta cells, raising cyclic AMP and glucose-dependent insulin release, and it lowers glucagon and slows gastric emptying. GLP-1 receptor only; no GIP or glucagon activity.
FDA approvals, with dates
| Date | What was approved | Record |
|---|---|---|
| 18 Sep 2014 | New molecular entity, glycemic control in adults with type 2 diabetes; 0.75 and 1.5 mg | BLA 125469, original |
| 21 Feb 2020 | Reduction of major adverse cardiovascular events in adults with type 2 diabetes with established cardiovascular disease or multiple risk factors (REWIND) | BLA 125469, S-033 |
| 3 Sep 2020 | 3 mg and 4.5 mg weekly doses | BLA 125469, S-036 |
| 17 Nov 2022 | Pediatric patients aged 10 and older with type 2 diabetes | BLA 125469, S-051 |
The cardiovascular indication is unusual in the class because REWIND enrolled mostly people without a prior cardiovascular event, so the label wording covers "multiple cardiovascular risk factors" as well as established disease.
Dosing as the label states it
- Adults: 0.75 mg once weekly to start. After 4 weeks, may increase to 1.5 mg. If more glycemic control is needed, increase in 1.5 mg steps after at least 4 weeks on the current dose, to a maximum of 4.5 mg weekly.
- Patients aged 10 to 17: 0.75 mg once weekly; may increase to 1.5 mg after at least 4 weeks. Maximum 1.5 mg.
- Missed dose: take it if at least 3 days (72 hours) remain before the next scheduled dose; otherwise skip.
- Any time of day, with or without food, in the abdomen, thigh or upper arm.
Pivotal trials and their numbers
| Trial | Population and duration | Result | PubMed |
|---|---|---|---|
| REWIND | 9,901 adults with type 2 diabetes, median HbA1c 7.2%, most without prior cardiovascular events; median 5.4 years | Primary composite 12.0% vs 13.4% (2.4 vs 2.7 per 100 person-years); hazard ratio 0.88 (0.79 to 0.99); all-cause mortality not significantly different (0.90, 0.80 to 1.01) | 31189511 |
| AWARD-5 | Adults with type 2 diabetes on metformin, against sitagliptin; 52 weeks | HbA1c -1.10 (1.5 mg) and -0.87 (0.75 mg) points vs -0.39 with sitagliptin; weight -3.03 and -2.60 kg vs -1.53 kg | 24742660 |
| SURPASS-CVOT (as comparator) | 13,299 adults with type 2 diabetes and cardiovascular disease | Primary endpoint 13.1% on dulaglutide 1.5 mg vs 12.2% on tirzepatide; hazard ratio 0.92 (0.83 to 1.01) favouring tirzepatide, not significant for superiority | 41406444 |
In REWIND 47.4% of the dulaglutide group reported a gastrointestinal adverse event during follow-up.
Adverse reactions from the label
| Adverse reaction | Placebo % | 0.75 mg % | 1.5 mg % |
|---|---|---|---|
| Nausea | 5.3 | 12.4 | 21.1 |
| Diarrhea | 6.7 | 8.9 | 12.6 |
| Vomiting | 2.3 | 6.0 | 12.7 |
| Abdominal pain | 4.9 | 6.5 | 9.4 |
| Decreased appetite | 1.6 | 4.9 | 8.6 |
| Dyspepsia | 2.3 | 4.1 | 5.8 |
| Fatigue | 2.6 | 4.2 | 5.6 |
The 3 mg and 4.5 mg doses were added later and have their own tables in the label's section 6.1.
Boxed warning and other warnings
The class boxed warning, in the dulaglutide wording: in male and female rats, a dose-related and duration-dependent increase in thyroid C-cell tumors after lifetime exposure; human relevance unknown; contraindicated with a personal or family history of medullary thyroid carcinoma or MEN 2. Section 5 covers pancreatitis, hypoglycemia with insulin or secretagogues, hypersensitivity, acute kidney injury, severe gastrointestinal reactions, retinopathy complications, gallbladder disease, and aspiration under anaesthesia.
Status and manufacturer
Approved and marketed by Eli Lilly, which also makes tirzepatide and orforglipron.
Where next
The other antibody-and-albumin approach to weekly dosing, albiglutide, was discontinued by its manufacturer; reading the two entries together shows why fusion proteins lost to fatty-acid peptides. The comparison table has a preset for the older GLP-1s.
Questions people ask
Is Trulicity approved for weight loss?
No. Trulicity is approved for glycemic control in type 2 diabetes from age 10 and for cardiovascular risk reduction in adults with type 2 diabetes. Weight loss in its trials was modest (about 3 kg at 1.5 mg over 52 weeks in AWARD-5) and it has no weight-management indication.
Why does dulaglutide matter for tirzepatide?
Because it was the comparator in SURPASS-CVOT, the trial behind tirzepatide's August 2026 cardiovascular indication. Tirzepatide was non-inferior to dulaglutide 1.5 mg, which itself had reduced cardiovascular events against placebo in REWIND.
Sources
- Drugs@FDA: BLA 125469 Trulicity (approval 2014-09-18; supplements 33, 36 and 51) Accessed September 4, 2026.
- Trulicity prescribing information, Eli Lilly, DailyMed set id 463050bd-2b1c-40f5-b3c3-0a04bb433309 Accessed September 4, 2026.
- Gerstein HC et al. Dulaglutide and cardiovascular outcomes in type 2 diabetes (REWIND). Lancet 2019. PubMed 31189511 Accessed September 4, 2026.
- Nauck M et al. Efficacy and safety of dulaglutide versus sitagliptin after 52 weeks in type 2 diabetes (AWARD-5). Diabetes Care 2014. PubMed 24742660 Accessed September 4, 2026.
- Cardiovascular outcomes with tirzepatide versus dulaglutide in type 2 diabetes (SURPASS-CVOT). N Engl J Med 2026. PubMed 41406444 Accessed September 4, 2026.
Canonical URL: https://formblendsglp1s.com/agents/dulaglutide. Written by the FormBlends editorial team. This page is educational and is not medical advice; see the medical disclaimer.