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Create Dulaglutide page (initial draft, MedTemplate, full inline cites)
 
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| generic = Dulaglutide
| generic = Dulaglutide
| brand = Trulicity
| brand = Trulicity
| structure = '''Fc-fusion construct''': two identical GLP-1 analog peptides (each modified at positions 8, 22, 36 for DPP-4 resistance and reduced immunogenicity) linked to a human IgG4 Fc fragment via a small glycine-rich peptide linker. The Fc tail drives the long half-life through FcRn recycling.<ref name="glaesner2010">Glaesner W, Vick AM, Millican R et al. (2010). Engineering and characterization of the long-acting glucagon-like peptide-1 analogue LY2189265, an Fc fusion protein. ''Diabetes Metab Res Rev'' 26(4):287–96. doi:10.1002/dmrr.1080</ref>
| structure =  
 
| classes = [[GLP-1 receptor agonist]] · [[Antidiabetic medicines|Antidiabetic]] · Fc-fusion biologic
| classes = [[GLP-1 receptor agonist]] · [[Antidiabetic medicines|Antidiabetic]] · Fc-fusion biologic
| mechanism = Selective long-acting agonist of the [[GLP-1 receptor]]. The Fc-IgG4 structure differentiates it pharmacokinetically (large protein cleared by FcRn-mediated recycling rather than albumin binding) but the receptor pharmacology is the standard GLP-1 RA profile.<ref name="glaesner2010"/>
| mechanism = Long-acting agonist of the [[GLP-1 receptor]]; Fc-fusion construct.
 
| uses = [[Type 2 diabetes mellitus]] · [[Cardiovascular risk reduction]] in T2DM
| uses = [[Type 2 diabetes mellitus]] · [[Cardiovascular risk reduction]] in T2DM
| starting_dose = 0.75 mg SC weekly<ref name="trulicity-label">US FDA. ''Trulicity (dulaglutide) prescribing information.'' Eli Lilly. https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/125469s044lbl.pdf</ref>
| starting_dose = 0.75 mg SC weekly<ref name="trulicity-label">US FDA. ''Trulicity (dulaglutide) prescribing information.'' Eli Lilly. https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/125469s044lbl.pdf</ref>
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Dulaglutide's principal clinical distinction is the [[REWIND trial|REWIND trial]], in which dulaglutide reduced major adverse cardiovascular events by 12% in T2DM patients ''including a majority with no prior cardiovascular disease'' — making it the first GLP-1 RA to demonstrate cardiovascular benefit in ''primary'' prevention.<ref name="rewind">Gerstein HC et al. (2019). Dulaglutide and cardiovascular outcomes in type 2 diabetes (REWIND). ''Lancet'' 394(10193):121–30. doi:10.1016/S0140-6736(19)31149-3</ref>
Dulaglutide's principal clinical distinction is the [[REWIND trial|REWIND trial]], in which dulaglutide reduced major adverse cardiovascular events by 12% in T2DM patients ''including a majority with no prior cardiovascular disease'' — making it the first GLP-1 RA to demonstrate cardiovascular benefit in ''primary'' prevention.<ref name="rewind">Gerstein HC et al. (2019). Dulaglutide and cardiovascular outcomes in type 2 diabetes (REWIND). ''Lancet'' 394(10193):121–30. doi:10.1016/S0140-6736(19)31149-3</ref>


| pharmacokinetics = The Fc-IgG4 fusion confers protection from renal filtration (~63 kDa, well above the glomerular cutoff) and triggers FcRn-mediated recycling, producing a terminal half-life of ~120 hours.<ref name="glaesner2010"/><ref name="trulicity-label"/> Cleared by proteolytic catabolism; no CYP-mediated metabolism. No dose adjustment for renal or hepatic impairment.<ref name="trulicity-label"/>
| pharmacokinetics = '''Chemistry'''. '''Fc-fusion construct''': two identical GLP-1 analog peptides (each modified at positions 8, 22, 36 for DPP-4 resistance and reduced immunogenicity) linked to a human IgG4 Fc fragment via a small glycine-rich peptide linker. The Fc tail drives the long half-life through FcRn recycling.<ref name="glaesner2010">Glaesner W, Vick AM, Millican R et al. (2010). Engineering and characterization of the long-acting glucagon-like peptide-1 analogue LY2189265, an Fc fusion protein. ''Diabetes Metab Res Rev'' 26(4):287–96. doi:10.1002/dmrr.1080</ref>
 
The Fc-IgG4 fusion confers protection from renal filtration (~63 kDa, well above the glomerular cutoff) and triggers FcRn-mediated recycling, producing a terminal half-life of ~120 hours.<ref name="glaesner2010"/><ref name="trulicity-label"/> Cleared by proteolytic catabolism; no CYP-mediated metabolism. No dose adjustment for renal or hepatic impairment.<ref name="trulicity-label"/>


The large molecular size limits both injection-site dispersion and oral bioavailability — dulaglutide cannot be formulated for oral use.
The large molecular size limits both injection-site dispersion and oral bioavailability — dulaglutide cannot be formulated for oral use.


| pharmacodynamics = At maintenance doses:
| pharmacodynamics = '''Receptor pharmacology'''. Selective long-acting agonist of the [[GLP-1 receptor]]. The Fc-IgG4 structure differentiates it pharmacokinetically (large protein cleared by FcRn-mediated recycling rather than albumin binding) but the receptor pharmacology is the standard GLP-1 RA profile.<ref name="glaesner2010"/>
 
At maintenance doses:
* HbA1c reduction of ~0.8–1.5 percentage points (1.5 mg/wk) and ~1.6–1.9 (4.5 mg/wk) in T2DM<ref name="award11">Frias JP, Bonora E, Nevarez Ruiz L et al. (2021). Efficacy and safety of dulaglutide 3 and 4.5 mg versus 1.5 mg in metformin-treated patients with type 2 diabetes (AWARD-11). ''Diabetes Care'' 44(3):765–73. doi:10.2337/dc20-1473</ref>
* HbA1c reduction of ~0.8–1.5 percentage points (1.5 mg/wk) and ~1.6–1.9 (4.5 mg/wk) in T2DM<ref name="award11">Frias JP, Bonora E, Nevarez Ruiz L et al. (2021). Efficacy and safety of dulaglutide 3 and 4.5 mg versus 1.5 mg in metformin-treated patients with type 2 diabetes (AWARD-11). ''Diabetes Care'' 44(3):765–73. doi:10.2337/dc20-1473</ref>
* Weight loss of ~2–5 kg, dose-dependent<ref name="award11"/>
* Weight loss of ~2–5 kg, dose-dependent<ref name="award11"/>

Revision as of 23:33, 16 May 2026

GLP-1 receptor agonist · Antidiabetic · Fc-fusion biologic
Dulaglutide
Trulicity
Dulaglutide is a weekly subcutaneous GLP-1 receptor agonist developed by Eli Lilly, marketed as Trulicity since September 2014.[1] Structurally distinct from the acylated peptide GLP-1 RAs (semaglutide, liraglutide), dulaglutide is an Fc-fusion biologic — its long half-life comes from FcRn-mediated recycling rather than albumin binding.[2] Dulaglutide's principal clinical distinction is the REWIND trial, in which dulaglutide reduced major adverse cardiovascular events by 12% in T2DM patients including a majority with no prior cardiovascular disease — making it the first GLP-1 RA to demonstrate cardiovascular benefit in primary prevention.[3]

Experience

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Problems

<indication ref="diabetes-type-2" author="MDElliottMD"/> <indication ref="cv-risk-t2dm" author="MDElliottMD"/>

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Titration strategies

Trulicity — standard T2DM titration0
0.75 mg SC weekly (starting and minimum effective dose)

→ 1.5 mg SC weekly × ≥4 weeks (most common maintenance) → 3 mg weekly × ≥4 weeks if additional HbA1c reduction needed → 4.5 mg weekly (max)[1]

The 0.75 mg starting dose is therapeutic (unlike the non-therapeutic ramps with semaglutide and tirzepatide). Most patients escalate to 1.5 mg within the first month.

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Effects

  • Early satiety (less pronounced than with semaglutide/tirzepatide at equipotent HbA1c reduction)[citation needed]
  • Nausea — usually mild-to-moderate, peaks in first 2–4 weeks[1]
  • Diarrhea / constipation[1]
  • Abdominal pain[1]
  • Decreased appetite[1]
  • Injection-site reactions — uncommon, generally mild[1]

GI tolerability is generally considered modestly better than weekly exenatide and comparable to or slightly better than weekly semaglutide at equivalent glycemic effect.[citation needed]

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Pharmacokinetics

Chemistry. Fc-fusion construct: two identical GLP-1 analog peptides (each modified at positions 8, 22, 36 for DPP-4 resistance and reduced immunogenicity) linked to a human IgG4 Fc fragment via a small glycine-rich peptide linker. The Fc tail drives the long half-life through FcRn recycling.[2]

The Fc-IgG4 fusion confers protection from renal filtration (~63 kDa, well above the glomerular cutoff) and triggers FcRn-mediated recycling, producing a terminal half-life of ~120 hours.[2][1] Cleared by proteolytic catabolism; no CYP-mediated metabolism. No dose adjustment for renal or hepatic impairment.[1]

The large molecular size limits both injection-site dispersion and oral bioavailability — dulaglutide cannot be formulated for oral use.

Pharmacodynamics

Receptor pharmacology. Selective long-acting agonist of the GLP-1 receptor. The Fc-IgG4 structure differentiates it pharmacokinetically (large protein cleared by FcRn-mediated recycling rather than albumin binding) but the receptor pharmacology is the standard GLP-1 RA profile.[2]

At maintenance doses:

  • HbA1c reduction of ~0.8–1.5 percentage points (1.5 mg/wk) and ~1.6–1.9 (4.5 mg/wk) in T2DM[4]
  • Weight loss of ~2–5 kg, dose-dependent[4]
  • 12% relative risk reduction in MACE (REWIND)[3]
  • Modest SBP reduction (~1–2 mmHg)[1]

    Interactions

No interactions reported yet.

Pregnancy and lactation

Avoid. Animal embryofetal toxicity is documented.[1] Discontinue at least 1 month before planned conception due to the ~5-day half-life. The pen contains no preservatives — single-dose only.

Monitoring

  • Baseline: HbA1c, weight, BP, renal function, lipid panel
  • Personal or family history of MTC or MEN2 — contraindicated, do not start[1]
  • Every 3 months for first year: HbA1c, weight, GI tolerability, signs of pancreatitis or gallbladder disease
  • Annual: renal function, lipids
  • Pre-procedure: hold weekly dose ≥7 days before any planned anesthesia[5]

    Patient counseling

  • Use the pre-filled pen as directed; the needle is hidden — patients do not see it. This is often the preferred GLP-1 RA for needle-averse patients.[citation needed]
  • GI side effects peak in first 2–4 weeks, then attenuate.[1]
  • If a weekly dose is missed: take within 3 days; if >3 days, skip and resume on the next regular day.[1]
  • Surgery: hold dose 7 days pre-op.[5]
  • Pregnancy planning: stop ≥1 month before trying to conceive.[1]

    Relevant anecdote

0

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Relevant Literature

No literature entries yet.

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See also

GLP-1 receptor agonist · Semaglutide · Liraglutide · Tirzepatide · Exenatide · Type 2 diabetes mellitus

References

  1. ↑ 1.00 1.01 1.02 1.03 1.04 1.05 1.06 1.07 1.08 1.09 1.10 1.11 1.12 1.13 1.14 1.15 1.16 1.17 1.18 1.19 1.20 1.21 1.22 1.23 1.24 US FDA. Trulicity (dulaglutide) prescribing information. Eli Lilly. https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/125469s044lbl.pdf
  2. ↑ 2.0 2.1 2.2 2.3 Glaesner W, Vick AM, Millican R et al. (2010). Engineering and characterization of the long-acting glucagon-like peptide-1 analogue LY2189265, an Fc fusion protein. Diabetes Metab Res Rev 26(4):287–96. doi:10.1002/dmrr.1080
  3. ↑ 3.0 3.1 Gerstein HC et al. (2019). Dulaglutide and cardiovascular outcomes in type 2 diabetes (REWIND). Lancet 394(10193):121–30. doi:10.1016/S0140-6736(19)31149-3
  4. ↑ 4.0 4.1 Frias JP, Bonora E, Nevarez Ruiz L et al. (2021). Efficacy and safety of dulaglutide 3 and 4.5 mg versus 1.5 mg in metformin-treated patients with type 2 diabetes (AWARD-11). Diabetes Care 44(3):765–73. doi:10.2337/dc20-1473
  5. ↑ 5.0 5.1 Kindel TL et al. (2024). Perioperative GLP-1 receptor agonist safety guidance. Surg Obes Relat Dis 20(12):1183–8.
Summary
Classes
GLP-1 receptor agonist · Antidiabetic · Fc-fusion biologic
Common uses
Pharmacy
Starting dose
0.75 mg SC weekly[1]
Preparations
Pre-filled single-dose pen: 0.75 / 1.5 / 3 / 4.5 mg[1]
US FDA Max
4.5 mg/wk SC[1]
Pharmacology
Routes
Subcutaneous (abdomen, thigh, upper arm)[1]
Onset
Glycemic effect within days; near-maximal HbA1c effect by 4 weeks at any given dose[1]
Duration
~7 days (weekly dosing)[1]
Half-life
~5 days (~120 h)[1]
Bioavailability
SC ~47%–65%[1]
Pregnancy
Avoid. Discontinue at least 1 month before planned pregnancy. Animal data show embryofetal harm.[1]
Legal status
Rx-only;[1] not a controlled substance
Purported mechanism
Long-acting agonist of the GLP-1 receptor; Fc-fusion construct.
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