Tirzepatide (Hero TZ): The Dual GIP/GLP-1 Agonist Explained

Key facts

Also known as	LY3298176
Class	GIP / GLP-1 receptor dual agonist
Developer	Eli Lilly and Company
Length	39 amino acids, GIP-based backbone
Half-life (human studies)	About 5 days
Status	FDA approved (Mounjaro 2022, Zepbound 2023)
Hero product	Hero TZ

For years, GLP-1 was the only incretin hormone anyone could turn into a working compound. GIP, its partner hormone, was written off. Then tirzepatide arrived as the first compound to activate both GIP and GLP-1 receptors, and its trial results changed how the field thinks about GIP. Researchers sometimes call it a “twincretin”.

This guide covers how tirzepatide is built, why it’s described as an imbalanced and biased agonist, and what the major SURPASS and SURMOUNT trials reported.

Origin story: the comeback of GIP

GIP (glucose-dependent insulinotropic polypeptide) is released from K cells in the upper small intestine after a meal. Along with GLP-1, it’s responsible for the incretin effect: the extra insulin released when glucose arrives through the gut instead of the bloodstream. Early work suggested GIP’s insulin effect was blunted in type 2 diabetes, so attention moved to GLP-1 alone.

Lilly’s discovery team took another look. The 2018 paper introducing LY3298176, later named tirzepatide, showed that a single peptide could engage both receptors and outperform a GLP-1 agonist alone in preclinical models and early human studies (Coskun et al., 2018). See our receptor explainer for how GIP and GLP-1 differ.

How tirzepatide is built

• Backbone: 39 amino acids, based on the native GIP sequence, with substitutions that add GLP-1 receptor activity.
• DPP-4 protection: Non-standard amino acids (aminoisobutyric acid, “Aib”) at key positions block breakdown by the DPP-4 enzyme, which inactivates native incretins within minutes.
• Albumin binding: A C20 fatty diacid attached through a linker binds albumin in the blood, stretching the half-life to about five days in human studies.

Retatrutide uses a very similar design strategy, then adds glucagon receptor activity. Compare the two in our retatrutide guide.

Why tirzepatide is “imbalanced” and “biased”

Two words come up constantly in tirzepatide research:

• Imbalanced: Tirzepatide is roughly as potent as native GIP at the GIP receptor, but considerably weaker than native GLP-1 at the GLP-1 receptor. It’s a GIP-leaning dual agonist.
• Biased: At the GLP-1 receptor, tirzepatide favors cAMP signaling over β-arrestin recruitment, which leads to less receptor internalization. That may help the receptor stay responsive over time (Willard et al., 2020).

Both properties are now design targets for the next generation of incretin compounds.

Tirzepatide’s two powers

GLP-1 receptor

Increases glucose-dependent insulin secretion, lowers post-meal glucagon, slows gastric emptying and acts on appetite pathways in the brain.

GIP receptor

Adds to insulin secretion and acts on fat tissue, where GIP signaling is involved in how fat is stored and handled. GIP receptors in the brain may also contribute to reduced food intake and better tolerance of GLP-1 effects.

What the SURPASS trials found (type 2 diabetes)

SURPASS was Lilly’s phase 3 program in type 2 diabetes. The most cited trial, SURPASS-2, compared three doses of tirzepatide with semaglutide 1 mg over 40 weeks in 1,879 adults. All three tirzepatide doses reduced HbA1c more than semaglutide, and reduced body weight more as well (Frías et al., 2021).

What the SURMOUNT trials found (obesity)

Trial	Population	Length	Key result
SURMOUNT-1	2,539 adults with obesity or overweight, no diabetes	72 weeks	Mean weight change −15.0%, −19.5% and −20.9% across doses vs −3.1% on placebo
SURMOUNT-OSA	Adults with obesity and obstructive sleep apnea	52 weeks	Significant reduction in apnea-hypopnea index vs placebo
SURMOUNT-5	Adults with obesity, head-to-head vs semaglutide 2.4 mg	72 weeks	−20.2% with tirzepatide vs −13.7% with semaglutide

Sources: Jastreboff et al., 2022; Malhotra et al., 2024; Aronne et al., 2025.

SURMOUNT-5 matters because it’s a true head-to-head trial, not a cross-trial comparison. It’s the clearest evidence so far that adding GIP receptor activity changes outcomes compared with a GLP-1 agonist alone.

Approvals and where tirzepatide stands

Unlike retatrutide, tirzepatide is an approved drug. The FDA approved it as Mounjaro for type 2 diabetes in May 2022 and as Zepbound for chronic weight management in November 2023, and later added an obstructive sleep apnea indication. That makes it the reference compound for most dual and triple agonist research.

Weak spots: what the safety data show

• Gastrointestinal effects (nausea, diarrhea, vomiting, constipation) were the most common, mostly during dose escalation, and similar in type to GLP-1 agonists.
• Class warnings shared with GLP-1 agonists include pancreatitis, gallbladder events and thyroid C-cell tumors seen in rodent studies.

Tirzepatide vs retatrutide vs semaglutide

	Semaglutide	Tirzepatide	Retatrutide
Receptors	GLP-1	GIP + GLP-1	GIP + GLP-1 + glucagon
Half-life	~7 days	~5 days	~6 days
Status	Approved	Approved	Investigational
Hero product	Hero SM	Hero TZ	Hero RT

Handling tirzepatide in the lab

Hero TZ ships lyophilized. Reconstitute it with bacteriostatic water using our reconstitution guide, and use the peptide calculator to get concentration and syringe units. Keep reconstituted vials refrigerated and protected from light.

Tirzepatide FAQ

Is tirzepatide a GLP-1?

It’s a GLP-1 receptor agonist and a GIP receptor agonist in one molecule, so it’s usually called a dual agonist rather than a GLP-1.

What is the difference between tirzepatide and semaglutide?

Semaglutide activates only the GLP-1 receptor. Tirzepatide also activates the GIP receptor, and in the head-to-head SURMOUNT-5 trial it produced greater weight reduction.

What is Hero TZ?

Hero TZ is Hero Peptides’ research-grade tirzepatide, supplied as a lyophilized powder for laboratory research use only.

References

1. Coskun T, et al. LY3298176, a novel dual GIP and GLP-1 receptor agonist for the treatment of type 2 diabetes mellitus: From discovery to clinical proof of concept. Mol Metab. 2018;18:3-14.
2. Willard FS, et al. Tirzepatide is an imbalanced and biased dual GIP and GLP-1 receptor agonist. JCI Insight. 2020;5(17):e140532.
3. Frías JP, et al. Tirzepatide versus semaglutide once weekly in patients with type 2 diabetes. N Engl J Med. 2021;385(6):503-515.
4. Jastreboff AM, et al. Tirzepatide once weekly for the treatment of obesity. N Engl J Med. 2022;387(3):205-216.
5. Malhotra A, et al. Tirzepatide for the treatment of obstructive sleep apnea and obesity. N Engl J Med. 2024;391(13):1193-1205.
6. Aronne LJ, et al. Tirzepatide as compared with semaglutide for the treatment of obesity. N Engl J Med. 2025;393(1):26-36.

For laboratory research use only. Not for human or veterinary use. This article summarizes published research and is not medical advice.