Body journey · 6 steps

Inside the body with Dulaglutide

Dulaglutide copies a gut hormone called GLP-1. It helps the pancreas release insulin when blood sugar is high and slows how fast the stomach empties. It is joined to part of an antibody, which keeps it in the body for days, so it is given once a week. It is approved for type 2 diabetes.

Scroll to follow it through the body

00Skin
How it is taken
Subcutaneous injection, once weekly, from a single-dose pen (approved use in type 2 diabetes).
01Bloodstream
Injected, then a slow, long-lasting presence in the blood
The medicine goes under the skin and slowly moves into the blood. It is joined to part of an antibody, which helps it stay in the body much longer. So it lasts for days, not minutes.
For experts +For experts −
After subcutaneous administration, time to peak concentration at steady state is 24 to 72 hours (median 48 hours); steady state is reached in 2 to 4 weeks with an accumulation ratio of about 1.56 and elimination half-life of about 5 days. The GLP-1 analogue is fused to a modified IgG4 Fc. In animal studies only (rats and cynomolgus monkeys), LY2189265 (the development code for dulaglutide) had a half-life of 1.5 to 2 days, and serum immunoreactivity representing active compound persisted for more than 6 days.[src][src]
02Pancreas
Switches on GLP-1 receptors in the pancreas
In the pancreas, dulaglutide fits the same lock as the natural GLP-1 hormone. This tells insulin-making cells to release insulin, mostly when blood sugar is high.
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Dulaglutide activates the GLP-1 receptor, a membrane receptor coupled to adenylyl cyclase, on pancreatic beta cells. Intracellular cAMP rises, leading to glucose-dependent insulin release. In patients with type 2 diabetes both first- and second-phase insulin secretion were increased versus placebo.[src]
03Pancreas
Turns down glucagon
Another pancreas hormone, glucagon, tells the liver to release sugar. Dulaglutide lowers glucagon, so less sugar is released.
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Dulaglutide decreases glucagon secretion. In a monotherapy trial, fasting glucagon fell by 1.71 and 2.05 pmol/L from baseline at week 26 at the two studied doses. In a separate clinical pharmacology study, fasting and 2-hour postprandial glucose were lower than placebo, an effect that can be seen after a single dose and was sustained after 6 weeks of dosing.[src]
04Stomach
Slows the stomach
Food leaves the stomach more slowly, so sugar from a meal enters the blood more gradually. This effect is biggest after the first dose and fades a bit over time.
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Dulaglutide delays gastric emptying. The delay is dose-dependent, attenuated with adequate dose escalation, largest after the first dose and diminishing with subsequent doses. The most common adverse reactions (5% or more) are nausea, diarrhoea, vomiting, abdominal pain and decreased appetite.[src]
05Heart
Fewer heart and stroke events in a large trial
In a large trial of people with type 2 diabetes, those given dulaglutide had somewhat fewer heart attacks, strokes or heart-related deaths than those given placebo. Scientists do not fully know how.
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In REWIND (9,901 participants, median 5.4 years), the primary composite of non-fatal myocardial infarction, non-fatal stroke or cardiovascular death occurred in 12.0% on dulaglutide versus 13.4% on placebo (HR 0.88, 95% CI 0.79-0.99, p=0.026). All-cause mortality did not differ significantly (HR 0.90, 95% CI 0.80-1.01). This is a human outcome result; the trial does not establish the mechanism.[src]
06Elsewhere
Broken down like any protein
Dulaglutide is a protein. The body eventually breaks it into amino acids, the small building blocks of all proteins.
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Dulaglutide is presumed to be degraded into component amino acids by general protein catabolism. Age, sex, race, body weight and renal or hepatic impairment did not have clinically relevant effects on its pharmacokinetics. Apparent population mean clearance is 0.142 L/h.[src]

Schematic animation — real structure where marked

Under the skin

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AI-generated illustration · not to scale

About these visuals

What is real and what is drawn

The scenes are schematic animations made for this page. Shapes, colours, speeds and sizes are chosen to explain, not to measure. Nothing is to scale.

Related structure: Experimental structure · cryo-EM 2.1 Å · PDB 6X18 (2020). It shows GLP-1(7-36)NH2 (native hormone), not Dulaglutide. From “Differential GLP-1R Binding and Activation by Peptide and Non-peptide Agonists.” Mol Cell 2020. RCSB PDB entry. The coordinates are experimental; the movement into place is illustrative.