Semaglutide vs Tirzepatide vs Retatrutide

Receptor coverage at a glance

• Semaglutide: GLP-1 only.
• Tirzepatide: GLP-1 + GIP (dual agonist).
• Retatrutide: GLP-1 + GIP + glucagon (triple agonist).

Semaglutide: the GLP-1 benchmark

Semaglutide put the whole GLP-1 class on the map. It's a long-acting GLP-1 receptor agonist with an engineered fatty-acid side chain that extends its half-life to roughly seven days — enabling once-weekly research dosing. GLP-1 receptor activation slows gastric emptying, enhances glucose-dependent insulin secretion, and engages central appetite-regulation pathways in the hypothalamus.

Research sizes: 3, 6, 12, 20, 30 mg. Research protocols almost universally titrate — starting low and scaling up over 4–8 weeks because GI-related endpoints scale with dose.

Tirzepatide: adding GIP

Tirzepatide activates both the GLP-1 and GIP receptors. GIP (glucose-dependent insulinotropic polypeptide) is a second incretin hormone. On its own, GIP has relatively modest effects — but combined with GLP-1 receptor activation, the dual signal produces stronger metabolic endpoints than GLP-1 alone.

The clinical/research question with tirzepatide has always been: does the GIP component contribute independent benefit, or does it just amplify GLP-1 signaling? Published research suggests both are happening — distinct and additive effects.

Research sizes: 15, 30, 60 mg. Weekly dosing. Titration schedules comparable to semaglutide.

Retatrutide: adding glucagon

Retatrutide goes further: GLP-1 + GIP + glucagon receptor. The glucagon receptor addition is mechanistically interesting because glucagon has opposite effects to insulin in certain tissues — raising glucose production but also increasing energy expenditure. The triple-agonist design balances these effects to produce stronger overall metabolic endpoints than either single or dual agonists.

Research sizes: 10, 15, 20, 30 mg. Weekly dosing.

Direct research comparisons

In head-to-head research models:

• Tirzepatide produces larger weight-loss endpoints than semaglutide at comparable doses.
• Retatrutide produces larger endpoints than tirzepatide in early research.
• Tolerance endpoints (GI effects) scale roughly with efficacy — more receptor coverage typically means more tolerability work in protocol design.

Where do cagrilintide stacks fit?

Cagrilintide is a long-acting amylin analog — a completely different receptor system. Amylin is co-secreted with insulin and regulates satiety and gastric emptying through its own pathway. Combining cagrilintide with a GLP-1-class compound adds a fourth receptor to the stack:

• Cagri-Sema — cagrilintide + semaglutide. Amylin + GLP-1.
• Cagri-Reta — cagrilintide + retatrutide. Amylin + GLP-1 + GIP + glucagon.

Cagri-Reta represents the broadest receptor coverage available in the current pre-blended research stacks.

Survodutide and mazdutide

Two dual agonists in a different pair than tirzepatide:

Survodutide

GLP-1 + glucagon (no GIP). A different take on the dual-agonist idea.

Mazdutide

GLP-1 + glucagon, developed from Chinese research pipelines.

Which one fits which research question?

• Baseline GLP-1 biology — semaglutide. Largest literature to compare against.
• Dual-agonist research — tirzepatide (GIP) or survodutide/mazdutide (glucagon).
• Triple-agonist research — retatrutide.
• Quad receptor coverage — Cagri-Reta.

Practical protocol notes

Weekly dosing is standard across the class. Reconstitute in bacteriostatic water to the target concentration — higher dilutions for smaller research doses, more concentrated for larger. Aliquot before freezing. Reconstituted vials keep ~28 days refrigerated.

Research-use notice

These compounds are not substitutes for prescribed pharmaceuticals. Every vial sold through Tidemaxxing is for laboratory research only. Nothing on this page is medical advice.