GLP-1 Comparison Matrix
A comprehensive, side-by-side comparison of the three major GLP-1 receptor agonist peptides covered in this database: Tirzepatide, Retatrutide, and Semaglutide.
Overview
| Feature |
Tirzepatide |
Retatrutide |
Semaglutide |
| Brand Name |
Mounjaro / Zepbound |
Unnamed (investigational) |
Ozempic / Wegovy / Rybelsus |
| Developer |
Eli Lilly |
Eli Lilly |
Novo Nordisk |
| Class |
GIP/GLP-1 dual agonist |
GIP/GLP-1/GCGR triple agonist |
Selective GLP-1 agonist |
| FDA Approval |
Yes (2022 T2D, 2023 obesity) |
Investigational (Phase 3) |
Yes (2017 T2D, 2021 obesity) |
| Route |
SC weekly |
SC weekly |
SC weekly / Oral daily |
| Half-life |
~5 days |
~6 days |
~7 days |
Chemical Profile Comparison
| Property |
Tirzepatide |
Retatrutide |
Semaglutide |
| CAS Number |
2023788-19-2 |
2381089-83-3 |
910463-68-2 |
| Molecular Formula |
C₂₂₅H₃₄₈N₄₈O₆₈ |
C₂₂₈H₃₅₄N₄₆O₆₈ |
C₁₈₇H₂₉₁N₄₅O₅₉ |
| Molecular Weight |
4813.45 g/mol |
4840.58 g/mol |
4113.58 g/mol |
| Sequence Length |
39 amino acids |
39 amino acids |
31 amino acids |
| Fatty Acid Modification |
C20 diacid |
C20 diacid |
C18 diacid |
| Purity (HPLC) |
≥ 98% |
≥ 98% |
≥ 98% |
Receptor Pharmacology Comparison
| Receptor |
Tirzepatide |
Retatrutide |
Semaglutide |
| GLP-1R EC50 |
0.06 nM |
0.09 nM |
0.04 nM |
| GIPR EC50 |
0.29 nM |
0.12 nM |
Inactive |
| GCGR EC50 |
Inactive |
0.26 nM |
Inactive |
| Receptor Activation Profile |
Balanced GIP/GLP-1 |
Balanced triple agonist |
Selective GLP-1 |
Pharmacokinetic Comparison
| Parameter |
Tirzepatide |
Retatrutide |
Semaglutide |
| Bioavailability (SC) |
~80% |
~75% |
~89% |
| Tmax |
8–24 h |
12–24 h |
12–24 h |
| Volume of Distribution |
~0.3 L/kg |
~0.25 L/kg |
~0.3 L/kg |
| Protein Binding |
~99% |
~99% |
~99% |
| Metabolism |
Proteolytic |
Proteolytic |
Proteolytic |
| Elimination |
Renal/Fecal |
Renal/Fecal |
Renal/Fecal |
Clinical Efficacy Comparison
| Endpoint |
Tirzepatide (15 mg) |
Retatrutide (12 mg) |
Semaglutide (2.4 mg) |
| HbA1c Reduction (T2D) |
2.1–2.4% |
1.6–2.2% (Phase 2) |
1.5–1.9% |
| Body Weight Reduction (T2D) |
11–15% |
10–15% (Phase 2) |
6–10% |
| Body Weight Reduction (Metabolic Research) |
15–22.5% |
17.5% |
14.9% |
| MACE Reduction |
Ongoing trials |
Ongoing trials |
20–26% reduction |
| Onset of Action |
2–4 weeks |
2–4 weeks |
2–4 weeks |
| Max Effect (Weight) |
40–60 weeks |
48–72 weeks |
60–68 weeks |
Safety Profile Comparison
| Adverse Event |
Tirzepatide |
Retatrutide |
Semaglutide |
| Nausea |
17–30% |
20–38% |
20–44% |
| Diarrhea |
13–23% |
15–28% |
13–28% |
| Vomiting |
6–10% |
8–15% |
5–15% |
| Pancreatitis |
~0.2% |
< 0.3% |
0.1–0.3% |
| Gallbladder events |
~0.4% |
~0.5% |
0.5–1.5% |
| Heart rate increase |
2–4 bpm |
2–4 bpm |
2–4 bpm |
| Discontinuation (GI) |
~5–8% |
~7–12% |
~5–10% |
Dosing Comparison
| Parameter |
Tirzepatide |
Retatrutide |
Semaglutide |
| Starting Dose |
2.5 mg/week |
1 mg/week |
0.25 mg/week |
| Maintenance Dose Range (Research) |
5–15 mg/week |
4–12 mg/week |
1.0–2.4 mg/week |
| Dose Escalation |
Every 4 weeks |
Every 4 weeks |
Every 4 weeks |
| Max Dose (Research) |
2.0 mg/week |
1.2 mg/week |
2.4 mg/week |
| Administration |
SC injection |
SC injection |
SC injection / Oral |
Selection Considerations
Choose Tirzepatide when:
- Research requires both GIP and GLP-1 receptor activation
- Superior weight loss efficacy is the primary endpoint
- Head-to-head comparison against selective GLP-1 agonism
Choose Retatrutide when:
- Triple receptor activation is of research interest
- Studying the glucagon receptor contribution to energy expenditure
- Investigating maximal weight loss potential
Choose Semaglutide when:
- A well-characterized selective GLP-1 agonist is needed
- Cardiovascular outcome research is the focus
- Oral administration route is required
Analytical Method Comparison
| Parameter |
Tirzepatide |
Retatrutide |
Semaglutide |
| HPLC Gradient |
20–60% B (30 min) |
25–65% B (30 min) |
20–60% B (30 min) |
| Retention Time |
~14–16 min |
~15–17 min |
~13–15 min |
| Column |
C18 (4.6×250 mm) |
C18 (4.6×250 mm) |
C18 (4.6×250 mm) |
| Detection |
UV 214 nm |
UV 214 nm |
UV 214 nm |
| MS Ionization |
ESI+ |
ESI+ |
ESI+ |
| Charge States |
+4 to +8 |
+4 to +8 |
+3 to +7 |
References
- Coskun T, et al. (2018). Dual GIP/GLP-1 agonist tirzepatide. Diabetes. DOI: 10.2337/db18-0027
- Coskun T, et al. (2022). Triple agonist retatrutide. Nature Metabolism. DOI: 10.1038/s42255-022-00647-2
- Frias JP, et al. (2021). Tirzepatide vs semaglutide (SURPASS-2). The Lancet. DOI: 10.1016/S0140-6736(21)01324-6
- Jastreboff AM, et al. (2022). Tirzepatide for obesity (SURMOUNT-1). NEJM. DOI: 10.1056/NEJMoa2206038
- Jastreboff AM, et al. (2023). Retatrutide for obesity management. NEJM. DOI: 10.1056/NEJMoa2301972
- Marso SP, et al. (2016). Semaglutide CV outcomes (SUSTAIN-6). NEJM. DOI: 10.1056/NEJMoa1607141
- Wilding JPH, et al. (2021). Semaglutide for obesity (STEP-1). NEJM. DOI: 10.1056/NEJMoa2032183
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