Dulaglutide vs Semaglutide

Both are once-weekly GLP-1 receptor agonists but achieve their half-life differently: dulaglutide is fused to an antibody Fc fragment, semaglutide binds albumin through a fatty-acid side chain.

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Dulaglutide

A once-weekly GLP-1 receptor agonist made by fusing two GLP-1 analogues to an antibody Fc fragment.

BEST STUDIED FOR

Incretin & metabolic

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	Dulaglutide	Semaglutide
The key difference	GLP-1 analogue fused to an Fc fragment	Fatty-acid acylated GLP-1 analogue
Class	Incretin & metabolic	Incretin & metabolic
Mechanism	Dulaglutide’s Fc fusion gives it a large size and slow clearance, allowing weekly dosing at the GLP-1 receptor with the class’s glucose-dependent insulin and glucagon effects.	Semaglutide is a GLP-1 analogue with amino-acid substitutions and a C18 fatty-diacid chain that binds albumin, extending its half-life to about a week.
Status	Approved for type 2 diabetes; the REWIND cardiovascular-outcomes trial is its landmark dataset.	Approved medicine (type 2 diabetes and chronic weight management) in many countries, with a large phase 3 programme (STEP, SUSTAIN, SELECT). Prescription-only in South Africa.
Reported safety signals	Class gastrointestinal effects; REWIND exploratory analyses also examined renal and cognitive outcomes.	Reviews document gastrointestinal effects as the most common; pancreatitis, gallbladder events and the effect on lean mass are active topics. Trials show weight regain after stopping.
A key study	REWIND measured major adverse cardiovascular events with dulaglutide versus placebo in type 2 diabetes. (Lancet 2019, PMID 31189511)	Reviews the safety profile of semaglutide across subcutaneous and oral formulations. (Front Endocrinol (Lausanne) 2021, PMID 34305810)

Dulaglutide has a cardiovascular-outcome trial (REWIND); semaglutide has the larger weight-management programme. Both are discussed here strictly as research compounds; nothing on this page is medical advice or a dosing guide.

REFERENCES (PUBMED)

[Dulaglutide] Dulaglutide and cardiovascular outcomes in type 2 diabetes (REWIND): a double-blind, randomised placebo-controlled trial — Lancet 2019. PMID 31189511
[Dulaglutide] Dulaglutide: A Review in Type 2 Diabetes — Drugs 2020. PMID 32002850
[Dulaglutide] Effect of dulaglutide on cognitive impairment in type 2 diabetes: an exploratory analysis of the REWIND trial — Lancet Neurol 2020. PMID 32562683
[Semaglutide] Safety of Semaglutide — Front Endocrinol (Lausanne) 2021. PMID 34305810
[Semaglutide] A systematic review of the effect of semaglutide on lean mass: insights from clinical trials — Expert Opin Pharmacother 2024. PMID 38629387
[Semaglutide] Effect of Continued Weekly Subcutaneous Semaglutide vs Placebo on Weight Loss Maintenance in Adults With Overweight or Obesity: The STEP 4 Randomized Clinical Trial — JAMA 2021. PMID 33755728

FREQUENTLY ASKED

What is the difference between Dulaglutide and Semaglutide?

Both are once-weekly GLP-1 receptor agonists but achieve their half-life differently: dulaglutide is fused to an antibody Fc fragment, semaglutide binds albumin through a fatty-acid side chain.

What is the regulatory status of Dulaglutide and Semaglutide?

Dulaglutide: Approved for type 2 diabetes; the REWIND cardiovascular-outcomes trial is its landmark dataset. Semaglutide: Approved medicine (type 2 diabetes and chronic weight management) in many countries, with a large phase 3 programme (STEP, SUSTAIN, SELECT). Prescription-only in South Africa.

What safety signals have been reported?

Dulaglutide: Class gastrointestinal effects; REWIND exploratory analyses also examined renal and cognitive outcomes. Semaglutide: Reviews document gastrointestinal effects as the most common; pancreatitis, gallbladder events and the effect on lean mass are active topics. Trials show weight regain after stopping.

Which studies is this comparison based on?

For Dulaglutide: “Dulaglutide and cardiovascular outcomes in type 2 diabetes (REWIND): a double-blind, randomised placebo-controlled trial” (PMID 31189511); “Dulaglutide: A Review in Type 2 Diabetes” (PMID 32002850); “Effect of dulaglutide on cognitive impairment in type 2 diabetes: an exploratory analysis of the REWIND trial” (PMID 32562683). For Semaglutide: “Safety of Semaglutide” (PMID 34305810); “A systematic review of the effect of semaglutide on lean mass: insights from clinical trials” (PMID 38629387); “Effect of Continued Weekly Subcutaneous Semaglutide vs Placebo on Weight Loss Maintenance in Adults With Overweight or Obesity: The STEP 4 Randomized Clinical Trial” (PMID 33755728).