Tirzepatide (Mounjaro) Explained: How the Dual GIP/GLP-1 Drug Works for Weight Loss

Tirzepatide (Mounjaro) Explained: How the Dual GIP/GLP-1 Drug Works for Weight Loss

Weight loss medicine changed in 2022. That's not hyperbole — it's what the data said when the SURMOUNT-1 trial results were published in the New England Journal of Medicine. A weekly injection called tirzepatide produced average weight reductions of up to 20.9% over 72 weeks in adults with obesity who did not have type 2 diabetes.¹ For context, that's roughly equivalent to losing 21 kg if you weigh 100 kg — from a once-weekly injection.

The drug behind those numbers is tirzepatide, sold under the brand name Mounjaro. This article explains exactly what it is, how it works at a biological level, and why its dual-receptor mechanism represents a meaningful clinical advance over earlier generation weight-loss medications.

What Is Tirzepatide?

Tirzepatide is a dual GIP/GLP-1 receptor agonist — a single molecule that activates two separate hormone receptors simultaneously. It was developed by Eli Lilly and Company and is administered as a once-weekly subcutaneous injection.

Two hormones are central to understanding how tirzepatide works:

• GLP-1 (glucagon-like peptide-1): A gut-derived incretin hormone released after eating. It stimulates insulin secretion, suppresses glucagon, slows gastric emptying, and — critically — signals the brain's satiety centres to reduce appetite.
• GIP (glucose-dependent insulinotropic polypeptide): Also released from the gut after meals. GIP has historically been less studied in the weight-loss context, but emerging evidence suggests it plays an important synergistic role alongside GLP-1 — amplifying insulin response and influencing fat metabolism and energy storage.²

Tirzepatide is a single peptide molecule engineered to bind and activate receptors for both hormones. This is distinct from earlier GLP-1 receptor agonists (like semaglutide), which act on the GLP-1 pathway alone.

The Dual Mechanism: Why Two Is Better Than One

To understand why the dual mechanism matters, it helps to see how the two pathways interact.

GLP-1 receptor activation reduces appetite, slows the movement of food through the stomach (increasing feelings of fullness), and stimulates glucose-dependent insulin secretion. GLP-1 agonists like semaglutide work on this pathway alone, which is why drugs like Ozempic and Wegovy have been clinically effective.

GIP receptor activation adds a separate but complementary layer. GIP receptors are found not just in the pancreas but also in adipose (fat) tissue, the brain, and bone. When GIP receptors in fat tissue are activated, the evidence suggests tirzepatide may improve the body's ability to store and utilise fat more efficiently — and at the brain level, GIP appears to augment the appetite-suppressive signal of GLP-1 rather than simply duplicate it.³

The net effect is a greater overall reduction in caloric intake and body weight than either pathway produces alone. Think of it as two independent braking systems working simultaneously, rather than pressing the same brake twice.

What Does the Clinical Evidence Show?

The headline data comes from SURMOUNT-1, the Phase 3 randomised controlled trial published in the New England Journal of Medicine in July 2022.¹

Study design:

• 2,539 adults with a BMI ≥30 (or ≥27 with at least one weight-related comorbidity) and without type 2 diabetes
• Randomised to once-weekly tirzepatide (5 mg, 10 mg, or 15 mg) or placebo
• Duration: 72 weeks
• All participants received lifestyle counselling

Key efficacy results:

| Dose | Average weight loss (%) | Average weight loss (kg, ~100 kg baseline) | |---|---|---| | Placebo | −3.1% | −3.1 kg | | 5 mg | −15.0% | −15.0 kg | | 10 mg | −19.5% | −19.5 kg | | 15 mg | −20.9% | −20.9 kg |

At the highest dose, 91% of participants achieved at least 5% weight loss, compared with 35% on placebo. More than half (57%) of participants on 15 mg tirzepatide lost 20% or more of their body weight — a threshold previously associated only with bariatric surgery outcomes.¹

All three doses were statistically superior to placebo (p<0.001).

How Does Tirzepatide Compare to Semaglutide?

Semaglutide 2.4 mg (Wegovy) is the best-known GLP-1 receptor agonist for weight management. In the STEP 1 trial, semaglutide 2.4 mg weekly produced an average weight loss of 14.9% over 68 weeks in adults without diabetes.⁴

Comparing across trials is imperfect (different populations, different durations), but the directionality is clear: tirzepatide at its two higher doses consistently outperformed semaglutide's benchmarks. The SURMOUNT-5 head-to-head trial, which directly compared tirzepatide 10 mg and 15 mg to semaglutide 2.4 mg, found tirzepatide produced approximately 47% greater relative weight loss than semaglutide at 72 weeks.⁵

The mechanistic explanation is intuitive: a molecule that activates two complementary weight-reduction pathways should, all else equal, produce a larger effect than one that activates only one.

How Is Tirzepatide Taken?

Tirzepatide is administered as a once-weekly subcutaneous injection — typically into the abdomen, thigh, or upper arm. It comes in pre-filled auto-injector pens.

Dosing follows a step-up protocol to minimise gastrointestinal side effects:

• Week 1–4: 2.5 mg weekly (initiation dose, not a therapeutic dose)
• Week 5–8: 5 mg weekly
• Thereafter, titrated upward by 2.5 mg increments every 4 weeks as tolerated
• Maintenance doses: 5 mg, 10 mg, or 15 mg weekly

Side Effects

The most commonly reported adverse effects are gastrointestinal in nature, consistent with GLP-1 class effects:

• Nausea (the most common, particularly during dose escalation)
• Diarrhoea
• Vomiting
• Constipation
• Reduced appetite

In SURMOUNT-1, the majority of GI adverse events were mild to moderate in severity and occurred most frequently during dose escalation. Approximately 4.3–7.4% of participants on active treatment discontinued due to adverse events (versus 2.6% on placebo).¹

Tirzepatide is contraindicated in individuals with a personal or family history of medullary thyroid carcinoma or Multiple Endocrine Neoplasia syndrome type 2. It should be used with caution in individuals with a history of pancreatitis.

Is Tirzepatide Right for You?

Tirzepatide represents a clinically significant advance in pharmacological weight management. The SURMOUNT-1 data places it among the most effective non-surgical interventions for obesity ever studied.

Whether it is appropriate for any individual depends on their full medical history, current medications, and clinical assessment. Tirzepatide is a prescription-only medicine. A qualified physician should evaluate candidacy, initiate dosing, and monitor ongoing treatment.

References

1. Jastreboff AM, et al. "Tirzepatide Once Weekly for the Treatment of Obesity." *N Engl J Med.* 2022;387(3):205–216. https://doi.org/10.1056/NEJMoa2206038
2. Nauck MA, Müller TD. "Incretin hormones and type 2 diabetes." *Diabetologia.* 2023;66(8):1319–1334. https://doi.org/10.1007/s00125-023-05956-x
3. Coskun T, et al. "LY3298176, a novel dual GIP and GLP-1 receptor agonist for the treatment of type 2 diabetes mellitus." *Mol Metab.* 2018;18:3–14. https://doi.org/10.1016/j.molmet.2018.09.009
4. Wilding JPH, et al. "Once-Weekly Semaglutide in Adults with Overweight or Obesity." *N Engl J Med.* 2021;384(11):989–1002. https://doi.org/10.1056/NEJMoa2032183
5. Wadden TA, et al. "SURMOUNT-5: Tirzepatide vs. Semaglutide for Weight Management." *N Engl J Med.* 2025. https://doi.org/10.1056/NEJMoa2410421

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This article is for educational purposes only. It does not constitute medical advice. Consult a licensed physician before starting any prescription medication.

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