Semaglutide
The most rigorously trialled compound in the peptide space. Multiple large phase 3 randomized trials with cardiovascular outcome data.
Metabolic & Weight
Dulaglutide
An approved weekly GLP-1 agonist for type 2 diabetes with a completed cardiovascular outcomes trial. Weight loss is modest compared with semaglutide or tirzepatide.
Overview
Dulaglutide is a GLP-1 molecule stitched onto a fragment of an antibody, which makes it large enough to avoid rapid clearance and lets it stay active for a week. It tells the pancreas to release insulin when blood glucose is high, suppresses glucagon, slows stomach emptying and reduces appetite. Because the insulin release is glucose-dependent, it does not by itself drive blood sugar too low.
A recombinant fusion of two GLP-1(7-37) analogue chains to a modified human IgG4 Fc via a peptide linker. Substitutions at positions 8, 22 and 36 confer DPP-4 resistance and reduce immunogenicity. The ~63 kDa size limits renal clearance and Fc-mediated recycling extends the half-life to roughly 5 days. Downstream signalling is canonical GLP-1R Gs-coupled cAMP/PKA activity in pancreatic beta cells, with central effects via hindbrain and hypothalamic GLP-1R populations. REWIND demonstrated a reduction in the composite MACE endpoint over median 5.4 years.
Research areas
Type 2 diabetesCardiovascular riskGlycaemic control
Dosing reported in the literature
Every protocol below is reproduced from a published study or approved labelling, with its source named. These are records of what was studied — not recommendations, and not a suggestion that any of them is appropriate for any person.
| Protocol as reported | Source |
|---|---|
| 0.75 mg once weekly starting dose, escalated to 1.5 mg, then optionally 3.0 mg and 4.5 mg | Approved product labelling |
| 1.5 mg once weekly for a median of 5.4 years in the cardiovascular outcomes trial | REWIND, The Lancet 2019 |
Trial status
Extensive phase 3 AWARD programme plus the REWIND cardiovascular outcomes trial, all completed and published.
Reported safety signals
- Nausea, diarrhoea and vomiting are the most common adverse effects, usually early and dose-related.
- Boxed warning for thyroid C-cell tumours based on rodent data; contraindicated with personal or family history of medullary thyroid carcinoma or MEN2.
- Pancreatitis has been reported; discontinue if suspected.
- Hypoglycaemia risk rises substantially when combined with sulfonylureas or insulin.
Common questions
How much weight does dulaglutide cause?
Roughly 2–4 kg on average in diabetes trials, rising a little at the 3.0 and 4.5 mg doses. That is meaningfully less than semaglutide 2.4 mg or tirzepatide, and dulaglutide is not approved for weight management.
Primary sources
- 01
Dulaglutide and cardiovascular outcomes in type 2 diabetes (REWIND): a double-blind, randomised placebo-controlled trial
- 02
Efficacy and safety of dulaglutide versus sitagliptin after 52 weeks in type 2 diabetes in a randomized controlled trial (AWARD-5)
- 03
Trulicity (dulaglutide) prescribing information
Medical disclaimer
This page is for informational and research purposes only. Nothing here constitutes medical advice. The compounds discussed are research chemicals. Consult a qualified clinician before starting any protocol.
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