Trulicity
Evidence Grade A — Regulatory approved. 1161 published studies. 73 registered clinical trials.
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Dulaglutide (sold as Trulicity) is a once-weekly injectable treatment for type 2 diabetes that mimics the gut hormone GLP-1 to help control blood sugar and promote modest weight loss. It became one of the most prescribed diabetes medications in the world, largely because the REWIND trial — the longest cardiovascular outcomes study for any GLP-1 drug — showed it also reduces the risk of heart attacks and strokes.
1,161 published studies: 735 human, 45 animal, 20 in-vitro, 308 reviews
Dulaglutide is marketed as Trulicity (approved September 2014) and has become one of the most prescribed GLP-1 treatments worldwide. The REWIND trial was a landmark study — it enrolled over 9,900 patients and followed them for a median of 5.4 years, making it the longest cardiovascular outcomes trial for any GLP-1 medication. REWIND showed a 12% reduction in major cardiovascular events.
Importantly, REWIND enrolled a broader patient population than previous cardiovascular trials, with only 31% having established heart disease at baseline, suggesting the cardiovascular benefit may extend beyond high-risk patients. While Trulicity's blood sugar and weight loss effects are more modest than semaglutide or tirzepatide, its long safety track record and extensive cardiovascular data make it a well-established treatment option.
Dulaglutide works through the same GLP-1 pathway as other medications in this class: it promotes insulin release when blood sugar is elevated, reduces the hormone that raises blood sugar, slows stomach emptying, and suppresses appetite. What makes it structurally different is that rather than using a fatty acid chain to extend its life in the body (like semaglutide and liraglutide), dulaglutide is physically attached to a large antibody fragment. This makes the molecule too large to be quickly filtered out by the kidneys, giving it a long enough duration for once-weekly dosing.
The REWIND trial followed over 9,900 patients for a median of 5.4 years and showed a 12% reduction in major cardiovascular events. Notably, REWIND enrolled a broader population than earlier cardiovascular trials (only 31% had existing heart disease), suggesting the heart benefits may apply to a wider range of people with diabetes. The trial also showed kidney-protective effects. However, dulaglutide has been substantially overtaken by newer treatments. In head-to-head comparisons, semaglutide and tirzepatide both deliver greater blood sugar control and significantly more weight loss. Trulicity sales peaked at $7.4 billion in 2022 but have declined as patients and doctors shift to these more potent alternatives. Dulaglutide remains a well-established option for patients who value its extensive long-term safety record and cardiovascular evidence.
Emulation of the REWIND Cardiovascular Outcomes Trial in Healthcare Claims Data.
A Study to Evaluate the Effect of Fasting Duration and Dulaglutide (LY2189265) Withholding on Gastric Retention in Participants With Type 2 Diabetes Mellitus
A Phase 3 Study of HS-20094 in Patients With T2DM
A Study of HDM1005 in Participants With T2DM Not Controlled With Diet/Exercise or Metformin
A Study of Dulaglutide (LY2189265) 3.0 mg and 4.5 mg in Pediatric Participants With Type 2 Diabetes Mellitus (AWARD-PEDS PLUS)
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Exenatide was the first GLP-1 receptor agonist approved anywhere, reaching the market as Byetta in April 2005. The once-weekly formulation Bydureon followed in 2012. Clinical trials showed blood sugar reductions (HbA1c) of 1.6–1.9% and modest weight loss of 2–4 kg. The EXSCEL cardiovascular outcomes trial, involving over 14,700 patients, showed a trend toward cardiovascular benefit but narrowly missed statistical significance. While exenatide was groundbreaking as the first in its class, it has been largely overtaken by newer GLP-1 treatments that offer greater efficacy, less frequent dosing, and proven cardiovascular benefits. It remains available and in clinical use, particularly in combination products.
Lixisenatide was marketed as Adlyxin in the US (approved July 2016), though it has since been discontinued in the US market. The ELIXA cardiovascular trial, involving over 6,000 patients, was the first cardiovascular outcomes trial for any GLP-1 medication to report results. It showed a neutral cardiovascular profile — neither harmful nor beneficial — meeting safety requirements but not demonstrating the heart benefits later shown by semaglutide and liraglutide. Lixisenatide found its primary clinical role in combination with basal insulin, marketed as Soliqua (lixisenatide plus insulin glargine). This combination addresses both fasting blood sugar (via insulin) and post-meal spikes (via lixisenatide) in a single daily injection. As a standalone treatment, it has been largely superseded by more potent GLP-1 medications.
Pramlintide is marketed as Symlin (approved March 2005) and remains the only approved amylin-based treatment. It is used alongside mealtime insulin in both type 1 and type 2 diabetes. Clinical trials showed modest blood sugar improvements (HbA1c reductions of 0.2–0.6%) and approximately 2.3 kg of weight loss — less dramatic than GLP-1 treatments but meaningful as an add-on therapy. Symlin carries a boxed warning for severe hypoglycaemia, particularly when combined with insulin, and requires careful dose adjustment. Practical uptake has been limited by the need for separate injections at each meal alongside existing insulin injections. Despite its modest clinical impact, pramlintide remains the only medication that addresses the amylin deficiency in diabetes, filling a distinct biological role that GLP-1 treatments do not cover.
