Dulaglutide: Difference between revisions
| [unchecked revision] | [unchecked revision] |
MDElliottMD (talk | contribs) Fix Cargo VARCHAR(300) overflow: blank structure, shorten mechanism, move chemistry/mechanism prose to PK/PD |
MDElliottMD (talk | contribs) Strip Category:MedCategory marker per interface-claude 2026-05-20 hygiene order: this page is a medicine, narrative, wiki-meta page, or stylesheet rather than a class-overview category, so it should not carry the MedCategory tag. Class memberships and other tags preserved. |
||
| (2 intermediate revisions by the same user not shown) | |||
| Line 18: | Line 18: | ||
| pregnancy = Avoid. Discontinue at least 1 month before planned pregnancy. Animal data show embryofetal harm.<ref name="trulicity-label"/> | | pregnancy = Avoid. Discontinue at least 1 month before planned pregnancy. Animal data show embryofetal harm.<ref name="trulicity-label"/> | ||
| legal = Rx-only;<ref name="trulicity-label"/> not a controlled substance | | legal = Rx-only;<ref name="trulicity-label"/> not a controlled substance | ||
| intro = Dulaglutide is a weekly subcutaneous [[GLP-1 receptor agonist]] developed by Eli Lilly, marketed as '''[[Trulicity]]''' since September 2014.<ref name="trulicity-label"/> Structurally distinct from the acylated peptide GLP-1 RAs ([[semaglutide]], [[liraglutide]]), dulaglutide is an Fc-fusion biologic | | intro = Dulaglutide is a weekly subcutaneous [[GLP-1 receptor agonist]] developed by Eli Lilly, marketed as '''[[Trulicity]]''' since September 2014.<ref name="trulicity-label"/> 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.<ref name="glaesner2010"/> | ||
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'' | 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 = '''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> | | 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> | ||
| Line 26: | Line 26: | ||
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 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 | 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.<ref name="glaesner2010"/> | | 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"/> | ||
| Line 36: | Line 36: | ||
* Modest SBP reduction (~1–2 mmHg)<ref name="trulicity-label"/> | * Modest SBP reduction (~1–2 mmHg)<ref name="trulicity-label"/> | ||
| indications = < | | indications = <problem ref="diabetes-type-2" author="MDElliottMD"/> | ||
< | <problem ref="cv-risk-t2dm" author="MDElliottMD"/> | ||
| dosing = <titration slug="trulicity-standard" author="MDElliottMD" title="Trulicity | | dosing = <titration slug="trulicity-standard" author="MDElliottMD" title="Trulicity, standard T2DM titration"> | ||
0.75 mg SC weekly (starting and minimum effective dose) | 0.75 mg SC weekly (starting and minimum effective dose) | ||
→ 1.5 mg SC weekly × ≥4 weeks (most common maintenance) | → 1.5 mg SC weekly × ≥4 weeks (most common maintenance) | ||
| Line 49: | Line 49: | ||
| effects = * '''Early satiety''' (less pronounced than with semaglutide/tirzepatide at equipotent HbA1c reduction){{Citation needed}} | | effects = * '''Early satiety''' (less pronounced than with semaglutide/tirzepatide at equipotent HbA1c reduction){{Citation needed}} | ||
* '''Nausea''' | * '''Nausea''', usually mild-to-moderate, peaks in first 2–4 weeks<ref name="trulicity-label"/> | ||
* '''Diarrhea / constipation'''<ref name="trulicity-label"/> | * '''Diarrhea / constipation'''<ref name="trulicity-label"/> | ||
* '''Abdominal pain'''<ref name="trulicity-label"/> | * '''Abdominal pain'''<ref name="trulicity-label"/> | ||
* '''Decreased appetite'''<ref name="trulicity-label"/> | * '''Decreased appetite'''<ref name="trulicity-label"/> | ||
* '''Injection-site reactions''' | * '''Injection-site reactions''', uncommon, generally mild<ref name="trulicity-label"/> | ||
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}} | 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}} | ||
| Line 59: | Line 59: | ||
| interactions = <pharmaInteractions/> | | interactions = <pharmaInteractions/> | ||
| pregnancy_details = Avoid. Animal embryofetal toxicity is documented.<ref name="trulicity-label"/> Discontinue at least 1 month before planned conception due to the ~5-day half-life. The pen contains no preservatives | | pregnancy_details = Avoid. Animal embryofetal toxicity is documented.<ref name="trulicity-label"/> 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 | | monitoring = * Baseline: HbA1c, weight, BP, renal function, lipid panel | ||
* Personal or family history of MTC or [[MEN2]] | * Personal or family history of MTC or [[MEN2]], '''contraindicated''', do not start<ref name="trulicity-label"/> | ||
* Every 3 months for first year: HbA1c, weight, GI tolerability, signs of [[pancreatitis]] or [[gallbladder disease]] | * Every 3 months for first year: HbA1c, weight, GI tolerability, signs of [[pancreatitis]] or [[gallbladder disease]] | ||
* Annual: renal function, lipids | * Annual: renal function, lipids | ||
* '''Pre-procedure''': hold weekly dose ≥7 days before any planned anesthesia<ref name="kindel2024">Kindel TL et al. (2024). Perioperative GLP-1 receptor agonist safety guidance. ''Surg Obes Relat Dis'' 20(12):1183–8.</ref> | * '''Pre-procedure''': hold weekly dose ≥7 days before any planned anesthesia<ref name="kindel2024">Kindel TL et al. (2024). Perioperative GLP-1 receptor agonist safety guidance. ''Surg Obes Relat Dis'' 20(12):1183–8.</ref> | ||
| counseling = * Use the pre-filled pen as directed; the needle is hidden | | 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.<ref name="trulicity-label"/> | * GI side effects peak in first 2–4 weeks, then attenuate.<ref name="trulicity-label"/> | ||
* If a weekly dose is missed: take within 3 days; if >3 days, skip and resume on the next regular day.<ref name="trulicity-label"/> | * If a weekly dose is missed: take within 3 days; if >3 days, skip and resume on the next regular day.<ref name="trulicity-label"/> | ||
| Line 80: | Line 80: | ||
}} | }} | ||
[[Category:GLP-1 receptor agonists]] | [[Category:GLP-1 receptor agonists]] | ||
[[Category:Antidiabetic medicines]] | [[Category:Antidiabetic medicines]] | ||
[[Category:Eli Lilly medicines]] | [[Category:Eli Lilly medicines]] | ||
Latest revision as of 18:00, 19 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]
+ Add a problem
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.
GLP-1 receptor agonist · Semaglutide · Liraglutide · Tirzepatide · Exenatide · Type 2 diabetes mellitus
Experience
No personal reports yet
No clinical reports yet
Log in to add your own experience.
Problems
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.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]
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
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
Relevant Literature
No literature entries yet.
Log in to submit relevant literature.
See also
References
- ↑ 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
- ↑ 2.0 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
- ↑ 3.0 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
- ↑ 4.0 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
- ↑ 5.0 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
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.