Evidence Grade A — Regulatory approved. 1207 published studies. 107 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.
Dulaglutide is also known by these brand and alternate names:
1,207 published studies: 753 human, 46 animal, 20 in-vitro, 326 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.
PeptideTrace tracks 107 registered clinical trials for Dulaglutide sourced from ClinicalTrials.gov.
Efficacy and Safety of Triple Therapy With Dulaglutide, SGLT2 Inhibitors, and Finerenone in Chinese Adults With Type 2 Diabetes and Chronic Kidney Disease
Emulation of the REWIND Cardiovascular Outcomes Trial in Healthcare Claims Data.
INcreTin-based thERapies for Cardiovascular Event PrevenTion in Patients With and Without ASCVD (INTERCEPT-ASCVD)
A Study to Evaluate the Effect of Fasting Duration and Dulaglutide (LY2189265) Withholding on Gastric Retention in Participants With Type 2 Diabetes Mellitus
Role of GLP1 RA Dulaglutide on Severe Intracranial Atherosclerosis
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Dulaglutide is a GLP-1 receptor agonist consisting of a modified GLP-1 analogue (90% homology to native GLP-1) covalently fused to a modified human IgG4 Fc fragment via a 16-amino-acid glycine-rich linker. The large molecular weight (~63 kDa) and Fc-mediated recycling via the neonatal Fc receptor (FcRn) produce a half-life of approximately 4–5 days, enabling once-weekly subcutaneous dosing.
Dulaglutide activates the GLP-1 receptor through the standard Gs/cAMP/PKA pathway, producing glucose-dependent insulin secretion, glucagon suppression, delayed gastric emptying, and central appetite suppression. The IgG4 Fc fragment reduces renal clearance (too large for glomerular filtration) and exploits FcRn-mediated endosomal recycling to extend circulation time. The linker length and flexibility were engineered to allow the GLP-1 moiety full receptor engagement despite the large Fc domain.
Dulaglutide is marketed as Trulicity (approved September 18, 2014). The REWIND trial (N=9,901; median follow-up 5.4 years—the longest GLP-1 RA cardiovascular outcomes trial) demonstrated a 12% reduction in 3-point MACE (HR 0.88; 95% CI 0.79–0.99; P=0.026). Notably, REWIND enrolled a broader population than other GLP-1 RA CVOTs, with approximately 69% of participants lacking established cardiovascular disease. Nonfatal stroke was reduced by 24% (HR 0.76; P=0.017). The AWARD trial program demonstrated HbA1c reductions of 0.62–1.77%, with AWARD-11 showing the 4.5 mg dose achieving −1.77% HbA1c reduction. Dulaglutide provides moderate weight loss of approximately 3–5 kg.
Linaclotide is marketed as Linzess (approved August 2012). It is taken as a daily oral capsule on an empty stomach, at least 30 minutes before the first meal. The recommended dose is 290 mcg for IBS-C and 72 or 145 mcg for chronic constipation. In clinical trials, approximately 34% of IBS-C patients met the composite improvement endpoint compared to 17% on placebo. Diarrhoea is the most common side effect (approximately 20%) and the leading reason for discontinuation. Linaclotide has a boxed warning against use in children under 6 years due to deaths in young mice, though no such events have been reported in humans. It competes with plecanatide (which targets the same pathway) and other IBS-C treatments.
Elamipretide (Forzinity) was approved by the FDA for Barth syndrome based on the TAZPOWER trial. The randomised crossover phase (12 patients) did not meet its primary endpoints, but the open-label extension (168 weeks) demonstrated durable improvements in walking distance and muscle strength that formed the basis for approval. Barth syndrome affects approximately 1 in 300,000–400,000 births. A larger Phase III trial in primary mitochondrial myopathy (218 patients, MMPOWER-3) did not meet its primary endpoint, and the drug was not approved for that broader indication. Elamipretide remains approved exclusively for Barth syndrome. See also SS-31 (#158) for the research compound context.
Glucagon has been available as an emergency injection since the 1960s and remains the standard rescue treatment for severe hypoglycaemia. Recent innovation has focused on making it easier to administer in emergencies. Baqsimi, approved in 2019, was the first needle-free option as a nasal powder. Gvoke, also approved in 2019, eliminated the need to mix and reconstitute the medication before injection — a significant advance since severe hypoglycaemia often impairs the ability to follow complex preparation steps. Dasiglucagon (Zegalogue), a next-generation stable liquid glucagon approved in 2021, further improved on the convenience of rescue administration. Beyond emergency rescue, glucagon's receptor is now a major research target — dual and triple agonists combining glucagon receptor activity with GLP-1 (such as survodutide and retatrutide) are in advanced clinical trials for obesity and metabolic disease.
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