Comparison

Two or three molecules, side by side.

Mechanism, how mature the indexed evidence is, regulatory status, and known safety concerns. Empty cells say “Not established.” Nothing here is a winner. A finding about one compound does not transfer to the next.

CJC-1295 with DAC is not its own entry. The no-DAC page is here because the FDA naming note says those structures are not the same chemical.

First compoundSecond compoundThird, optional

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Classification

Semaglutide: GLP-1 receptor agonist, albumin-binding analog. Pharmaceutical, not a typical research peptide.
Tirzepatide: Dual GIP and GLP-1 receptor agonist. Pharmaceutical.
Retatrutide: Investigational GLP-1, GIP, and glucagon receptor agonist

Form on the page

Semaglutide: The approved products are solutions or tablets. Research material is often a lyophilized powder and is not equivalent.
Tirzepatide: Approved form is a solution in a pen. Research catalogs often sell lyophilized powder.
Retatrutide: Lyophilized powder in research catalogs. The trial drug is the sponsor’s formulation.

Mechanism

Semaglutide: GLP-1 receptor activation slows gastric emptying, reduces appetite, and supports glucose-dependent insulin release. The approved effect is on blood sugar and body weight. Muscle loss can accompany the weight loss if protein and loading are ignored — that is physiology, not a side quest.
Tirzepatide: Hits both incretin receptors. Appetite, gastric emptying, and glucose-dependent insulin all move. In trials it produced larger average weight loss than semaglutide, with a similar GI adverse-event shape.
Retatrutide: The glucagon-receptor piece is the difference from tirzepatide. It adds energy-expenditure signaling on top of incretin appetite effects, which is also why heart rate and liver enzymes get more attention in the trial papers.

What the research is about

Semaglutide: This is an approved drug (Ozempic, Wegovy, Rybelsus) with a real label, real titration, and real contraindications, including a boxed warning about thyroid C-cell tumors from rodent data. Research vials and compounded copies are not those products. The FDA has repeatedly warned about unapproved semaglutide.
Tirzepatide: Approved as Mounjaro (type 2 diabetes) and Zepbound (weight management), with a labeled titration and a thyroid C-cell tumor boxed warning from rodent data. A lyophilized research vial is not a pen.
Retatrutide: TRIUMPH-1 (NEJM, online 29 September 2026, journal issue 5 November 2026) randomized 2,339 adults with obesity and no diabetes to once-weekly retatrutide 4, 9, or 12 mg or placebo for 80 weeks. Primary comparisons were the 9 mg and 12 mg groups versus placebo. Mean weight change was −17.6%, −23.7%, and −25.0% versus −3.9% with placebo. Pain fell more in 574 participants with knee osteoarthritis, and apnea–hypopnea events fell more in 243 with obstructive sleep apnea. Gastrointestinal effects were the common adverse events. The trial drug is the sponsor’s formulation. It is not a research vial, and it is not an approval.

Evidence maturity

Semaglutide: A randomized trial of a defined product is indexed. That is not a blanket efficacy claim.
Tirzepatide: Not established in this index. A missing entry is not proof that no papers exist, and it is not proof of safety.
Retatrutide: A randomized trial is indexed and the compound is still investigational.

Indexed human findings

Semaglutide: STEP 1: phase 3 randomized, placebo-controlled trial of once-weekly semaglutide 2.4 mg in adults with overweight or obesity. It studies the approved medicine, not a research-catalog vial. Effect sizes live in the paper; they are not recopied here.
Tirzepatide: Not established.
Retatrutide: TRIUMPH-1: phase 3, randomized, double-blind, 80-week trial. 2,339 adults with obesity without diabetes were assigned once-weekly retatrutide 4 mg, 9 mg, 12 mg, or placebo. Primary comparisons were 9 mg and 12 mg versus placebo. Mean weight change was −17.6%, −23.7%, and −25.0% versus −3.9% with placebo. In 574 participants with knee osteoarthritis, pain scores fell more than with placebo. In 243 with obstructive sleep apnea, apnea–hypopnea events fell more than with placebo. The most common adverse events were gastrointestinal. A published trial is not an approval.

Safety notes on this site

Semaglutide: Nausea, vomiting, constipation, and diarrhea are the labeled center of the adverse-event table, worst during escalation. Gallbladder disease, pancreatitis, and possible worsening of diabetic retinopathy are labeled concerns. A resting heart-rate bump is described. Injection-site redness happens and is usually local. Severe upper-abdominal pain, especially through to the back, is a stop-and-get-care symptom on the label (pancreatitis). Dehydration from vomiting is how people end up in trouble, not the nausea itself.
Tirzepatide: Nausea, diarrhea, decreased appetite, vomiting, and constipation dominate the label. Gallbladder events and pancreatitis are in the warnings. Heart rate can rise modestly. Injection-site reactions are usually mild. Same abdominal-pain rule as other incretins: severe, persistent, radiating pain is not “normal GI.”
Retatrutide: Nausea and other GI effects, as with the rest of this class. Heart-rate elevation was notable in published trial data. Skin sensitivity or dysesthesia has been discussed in trial reporting more than with semaglutide. There is no approved label to hide behind. Trial eligibility excluded a lot of people you cannot see from a vial. Persistent tachycardia, severe abdominal pain, or fainting is an emergency, not a titration event.

Regulatory status

Semaglutide: United States: FDA-approved medicine in named products (Ozempic, Wegovy, Rybelsus) for indications on those labels, including type 2 diabetes and chronic weight management. A research vial is not those products. Check the current label before relying on the indication list.
Tirzepatide: United States: FDA-approved medicine as Mounjaro (type 2 diabetes; first approved 2022) and Zepbound (chronic weight management; first approved 2023). Later label changes exist. A lyophilized research vial is not those pens.
Retatrutide: United States: Investigational. TRIUMPH-1 was published online in the New England Journal of Medicine on 29 September 2026 and issued on 5 November 2026. It is a phase 3 trial, not an approval. No FDA-approved retatrutide product was identified in this review.

Human pharmacokinetics

Semaglutide: Not established in this index.
Tirzepatide: Not established in this index.
Retatrutide: Not established in this index.

Still unanswered

Semaglutide: Controlled human outcomes for this exact substance are not established in this index. A mechanism, a nickname, or a supplier claim is not a result.
Tirzepatide: Controlled human outcomes for this exact substance are not established in this index. A mechanism, a nickname, or a supplier claim is not a result.
Retatrutide: Whether regulators will approve any product, and for which indication. Whether the trial’s gastrointestinal and heart-rate findings look the same outside the sponsor’s formulation. Long-term outcomes past the 80 weeks reported in TRIUMPH-1.

	Semaglutide	Tirzepatide	Retatrutide
Classification	GLP-1 receptor agonist, albumin-binding analog. Pharmaceutical, not a typical research peptide.	Dual GIP and GLP-1 receptor agonist. Pharmaceutical.	Investigational GLP-1, GIP, and glucagon receptor agonist
Form on the page	The approved products are solutions or tablets. Research material is often a lyophilized powder and is not equivalent.	Approved form is a solution in a pen. Research catalogs often sell lyophilized powder.	Lyophilized powder in research catalogs. The trial drug is the sponsor’s formulation.
Mechanism	GLP-1 receptor activation slows gastric emptying, reduces appetite, and supports glucose-dependent insulin release. The approved effect is on blood sugar and body weight. Muscle loss can accompany the weight loss if protein and loading are ignored — that is physiology, not a side quest.	Hits both incretin receptors. Appetite, gastric emptying, and glucose-dependent insulin all move. In trials it produced larger average weight loss than semaglutide, with a similar GI adverse-event shape.	The glucagon-receptor piece is the difference from tirzepatide. It adds energy-expenditure signaling on top of incretin appetite effects, which is also why heart rate and liver enzymes get more attention in the trial papers.
What the research is about	This is an approved drug (Ozempic, Wegovy, Rybelsus) with a real label, real titration, and real contraindications, including a boxed warning about thyroid C-cell tumors from rodent data. Research vials and compounded copies are not those products. The FDA has repeatedly warned about unapproved semaglutide.	Approved as Mounjaro (type 2 diabetes) and Zepbound (weight management), with a labeled titration and a thyroid C-cell tumor boxed warning from rodent data. A lyophilized research vial is not a pen.	TRIUMPH-1 (NEJM, online 29 September 2026, journal issue 5 November 2026) randomized 2,339 adults with obesity and no diabetes to once-weekly retatrutide 4, 9, or 12 mg or placebo for 80 weeks. Primary comparisons were the 9 mg and 12 mg groups versus placebo. Mean weight change was −17.6%, −23.7%, and −25.0% versus −3.9% with placebo. Pain fell more in 574 participants with knee osteoarthritis, and apnea–hypopnea events fell more in 243 with obstructive sleep apnea. Gastrointestinal effects were the common adverse events. The trial drug is the sponsor’s formulation. It is not a research vial, and it is not an approval.
Evidence maturity	A randomized trial of a defined product is indexed. That is not a blanket efficacy claim.	Not established in this index. A missing entry is not proof that no papers exist, and it is not proof of safety.	A randomized trial is indexed and the compound is still investigational.
Indexed human findings	STEP 1: phase 3 randomized, placebo-controlled trial of once-weekly semaglutide 2.4 mg in adults with overweight or obesity. It studies the approved medicine, not a research-catalog vial. Effect sizes live in the paper; they are not recopied here.	Not established.	TRIUMPH-1: phase 3, randomized, double-blind, 80-week trial. 2,339 adults with obesity without diabetes were assigned once-weekly retatrutide 4 mg, 9 mg, 12 mg, or placebo. Primary comparisons were 9 mg and 12 mg versus placebo. Mean weight change was −17.6%, −23.7%, and −25.0% versus −3.9% with placebo. In 574 participants with knee osteoarthritis, pain scores fell more than with placebo. In 243 with obstructive sleep apnea, apnea–hypopnea events fell more than with placebo. The most common adverse events were gastrointestinal. A published trial is not an approval.
Safety notes on this site	Nausea, vomiting, constipation, and diarrhea are the labeled center of the adverse-event table, worst during escalation. Gallbladder disease, pancreatitis, and possible worsening of diabetic retinopathy are labeled concerns. A resting heart-rate bump is described. Injection-site redness happens and is usually local. Severe upper-abdominal pain, especially through to the back, is a stop-and-get-care symptom on the label (pancreatitis). Dehydration from vomiting is how people end up in trouble, not the nausea itself.	Nausea, diarrhea, decreased appetite, vomiting, and constipation dominate the label. Gallbladder events and pancreatitis are in the warnings. Heart rate can rise modestly. Injection-site reactions are usually mild. Same abdominal-pain rule as other incretins: severe, persistent, radiating pain is not “normal GI.”	Nausea and other GI effects, as with the rest of this class. Heart-rate elevation was notable in published trial data. Skin sensitivity or dysesthesia has been discussed in trial reporting more than with semaglutide. There is no approved label to hide behind. Trial eligibility excluded a lot of people you cannot see from a vial. Persistent tachycardia, severe abdominal pain, or fainting is an emergency, not a titration event.
Regulatory status	United States: FDA-approved medicine in named products (Ozempic, Wegovy, Rybelsus) for indications on those labels, including type 2 diabetes and chronic weight management. A research vial is not those products. Check the current label before relying on the indication list.	United States: FDA-approved medicine as Mounjaro (type 2 diabetes; first approved 2022) and Zepbound (chronic weight management; first approved 2023). Later label changes exist. A lyophilized research vial is not those pens.	United States: Investigational. TRIUMPH-1 was published online in the New England Journal of Medicine on 29 September 2026 and issued on 5 November 2026. It is a phase 3 trial, not an approval. No FDA-approved retatrutide product was identified in this review.
Human pharmacokinetics	Not established in this index.	Not established in this index.	Not established in this index.
Still unanswered	Controlled human outcomes for this exact substance are not established in this index. A mechanism, a nickname, or a supplier claim is not a result.	Controlled human outcomes for this exact substance are not established in this index. A mechanism, a nickname, or a supplier claim is not a result.	Whether regulators will approve any product, and for which indication. Whether the trial’s gastrointestinal and heart-rate findings look the same outside the sponsor’s formulation. Long-term outcomes past the 80 weeks reported in TRIUMPH-1.