Introduction

Not a fan of needles? You may be considering Rybelsus, the first oral GLP-1 medication, as an alternative to injectable options like Zepbound.

But how do they compare when it comes to weight loss, side effects, and real-world results?

In this blog, we break down Zepbound vs Rybelsus so you can choose the right GLP-1 therapy based on your lifestyle, goals, and preferences.

Quick Comparison

Feature	Zepbound	Rybelsus
Active Ingredient	Tirzepatide	Semaglutide (oral)
Hormone Type	GLP-1 + GIP	GLP-1 only
Administration	Weekly injection	Daily oral tablet
FDA Approved For	Weight loss	Type 2 diabetes only
Avg. Weight Loss	15–22.5% of body weight	5–10% (off-label)

Active Ingredient & Mechanism

Zepbound (tirzepatide)

• Dual action: GLP-1 + GIP

• Suppresses appetite, slows digestion, and improves insulin sensitivity

• Leads to more dramatic weight and fat loss

Rybelsus (semaglutide oral)

• Activates only GLP-1

• Works similarly to Ozempic, but in pill form

• Best results seen at 14 mg/day, the highest dose

Learn more: How GLP-1 Medications Work

Weight Loss Comparison

Medication	Avg. Weight Loss	Duration	Notes
Zepbound	Up to 22.5%	72 weeks	FDA-approved for weight loss
Rybelsus	5–10% (off-label)	26–52 weeks	FDA-approved for diabetes

Zepbound SURMOUNT-1 Study – NEJM

Rybelsus PIONEER Trials

Zepbound consistently produces more weight loss, but Rybelsus may still help some users who prefer pills.

Convenience: Pill vs. Injection

Factor	Zepbound	Rybelsus
Frequency	1x per week	1x daily
How to Take	Self-injection	Oral pill—empty stomach only
Timing Restrictions	None	Must take 30 min before food or drink

Rybelsus must be taken first thing in the morning with water, on an empty stomach—this can be hard to follow consistently.

Side Effects

Both medications may cause:

• Nausea

• Constipation

• Fatigue

• Bloating or stomach upset

Rybelsus side effects may feel more consistent due to daily dosing, while Zepbound’s may spike after each weekly injection but fade faster.

FDA Approval & Insurance

Medication	FDA Approved For	Covered for Weight Loss?	Savings Options
Zepbound	Weight loss	With criteria	Zepbound Savings
Rybelsus	Type 2 diabetes	No (off-label only)	Rybelsus Card

Rybelsus is often NOT covered for weight loss unless you have a diabetes diagnosis. Zepbound is FDA-approved for obesity and more likely to be approved by insurance when criteria are met.

Who Should Choose Zepbound?

Great choice if you:

• Want maximum weight loss

• Prefer weekly dosing over daily routines

• Need help with insulin resistance or PCOS

• Can tolerate injectable medications

Who Should Choose Rybelsus?

May be best if you:

• Refuse or fear injections

• Have mild weight loss goals

• Have Type 2 diabetes

• Want to try a pill before committing to injectables

Final Thoughts

Zepbound offers greater weight loss and metabolic benefits, but Rybelsus provides a needle-free option for those looking to ease into GLP-1 therapy. Your best choice depends on your lifestyle, preferences, and how aggressively you want to lose weight.

Zepbound = stronger results, weekly injection
Rybelsus = daily pill, easier for injection-averse users
Both can reduce appetite and improve blood sugar

Visit our GLP-1 Comparison Hub for downloadable charts, side-by-side guides, and a free GLP-1 decision quiz.