Foundayo vs. Zepbound: a daily GLP-1 pill against a weekly shot

Foundayo is orforglipron, approved on April 1, 2026. It is a small, non-peptide molecule that activates the GLP-1 receptor. That structure lets it work as an ordinary tablet, swallowed with or without food at any time of day, per its label. Doses start at 0.8 mg daily, then 2.5 mg and 5.5 mg, each for at least 30 days. They can then rise to 9, 14.5 or 17.2 mg. Tablets are stored at room temperature.

Zepbound is tirzepatide, a peptide that activates both GIP and GLP-1 receptors. It is injected under the skin once a week. It starts at 2.5 mg and rises by 2.5 mg every 4 weeks or more to a 5, 10 or 15 mg maintenance dose. Zepbound is also approved for obstructive sleep apnea with obesity, which Foundayo is not.

No trial has compared Foundayo with Zepbound, so the numbers below come from separate studies with different participants.

Foundayo: ATTAIN-1 (NEJM 2025) enrolled 3,127 adults with obesity and no diabetes for 72 weeks. Counting everyone randomized, average weight change was −7.5%, −8.4% and −11.2% on the three doses, versus −2.1% on placebo. The top trial dose matches the 17.2 mg tablet. At that dose, 54.6% lost at least 10% of body weight, versus 12.9% on placebo. Lilly reports 12.4% for people who stayed on the top dose. Side effects led 5.3% to 10.3% of orforglipron users to stop, versus 2.7% on placebo.

Zepbound: SURMOUNT-1 (NEJM 2022) also ran 72 weeks and reported −15.0%, −19.5% and −20.9% at 5, 10 and 15 mg, against −3.1% on placebo.

Switching evidence. ATTAIN-MAINTAIN (Nature Medicine, 2026) moved people from tirzepatide or semaglutide to orforglipron or placebo for 52 weeks. People coming off tirzepatide kept an estimated 74.7% of their weight reduction on orforglipron, versus 49.2% on placebo. For people coming off semaglutide, the figures were 79.3% versus 37.6%. There was no arm that stayed on the injection, so it cannot show how the pill compares with continuing Zepbound.

Stomach effects dominate both, and they are most common during dose increases. At the top doses, compared with placebo in each program:

• Nausea: Foundayo 17.2 mg 35% vs 10%; Zepbound 15 mg 28% vs 8%
• Vomiting: 24% vs 4%; 13% vs 2%
• Diarrhea: 25% vs 11%; 23% vs 8%
• Constipation: 24% vs 9%; 11% vs 5%

About 10% stopped Foundayo 17.2 mg because of side effects, versus 6.7% on Zepbound 15 mg, per the two labels.

Interactions differ. Foundayo is capped at 9 mg with strong CYP3A4 inhibitors, such as clarithromycin. Simvastatin should not exceed 20 mg. Birth-control pills need backup for 30 days after starting and after each increase; Zepbound's label says 4 weeks. Both carry thyroid tumor boxed warnings. Orforglipron did not cause tumors in rodents, but the label keeps the warning and the MTC and MEN2 contraindication.

Zepbound may be the better fit if you want the larger average weight effect, are comfortable injecting once a week, and have fridge space. It is also the only one of the two approved for obstructive sleep apnea with obesity.

Foundayo may be the better fit if needles are the barrier or a fixed weekly day does not suit you. It also fits if you travel often, since it does not need refrigeration. It may suit people who have already lost weight on an injection and want an oral way to maintain it. ATTAIN-MAINTAIN supports that use, though not against continuing the injection.

Check your medicines first with Foundayo. Several common drugs interact with it through CYP3A4, and the dose cap or dose change matters.

Neither fits with a personal or family history of medullary thyroid carcinoma or MEN2, pregnancy, or a past serious allergic reaction to either drug. Foundayo is filled by LillyDirect at $149 for 30 days of the 0.8 mg starting tablet [usetemi.com/medications/foundayo, verified Sep 28, 2026].