GLP-1 Trial Results Q2 2026: ATTAIN-MAINTAIN, ATTAIN-2 & Foundayo Updates

This is the second quarterly digest of GLP-1 receptor-agonist and incretin-multiagonist trial activity. It captures every peer-reviewed Phase 3 readout, FDA approval, label update, and meaningful trial-registry status change that landed between January 1, 2026 and May 23, 2026. Each PMID was verified live against PubMed E-utilities and each NCT ID was verified live against the ClinicalTrials.gov v2 API on the publication date. The first quarter’s headline was the FDA approval of Foundayo (orforglipron) on April 1, 2026 — the first oral small-molecule GLP-1 receptor agonist approved for chronic weight management. The second was the ATTAIN-MAINTAIN Phase 3b weight-maintenance readout, the first prospective discontinuation-vs-continuation Phase 3 of an oral GLP-1^[2]. New label updates for Wegovy, Zepbound, and Foundayo all published to DailyMed within the quarter. We refresh this digest each quarter.

Recent positive Phase 3 readouts

Four major Phase 3 readouts published or formally indexed in PubMed during the Q2 2026 window. Each was anchored to a registered NCT ID and a peer-reviewed primary publication before we cited it.

ATTAIN-MAINTAIN (orforglipron)

Published: May 13, 2026, Nature Medicine^[2].
Registry: NCT06584916, status COMPLETED; primary completion 2025-11-21 (actual)^[15].
Design: phase 3b, randomized, double-blind, placebo-controlled, withdrawal-style maintenance trial. After a ~36-week lead-in on open-label orforglipron, participants who reached a target body-weight reduction were randomized 1:1 to continue orforglipron or switch to placebo for an additional maintenance period.
Topline: participants who continued orforglipron maintained their lead-in weight loss; participants randomized to placebo regained a meaningful fraction of the lost weight, consistent with the published pattern from injectable GLP-1 discontinuation studies. The clinically important takeaway: oral orforglipron behaves the same way as injectable semaglutide and tirzepatide after discontinuation — weight regain is expected, supporting a chronic, indefinite-duration treatment paradigm.

ATTAIN-2 (orforglipron in T2D)

Published: Lancet, print 2026 Dec 20, e-pub 2025 Nov 20^[3].
Registry: NCT05872620, status COMPLETED; primary completion 2025-08-08 (actual)^[15].
Design: phase 3, double-blind, randomized, multicentre, placebo-controlled, 72-week trial of three doses of orforglipron (3 mg, 12 mg, 36 mg) in adults with type 2 diabetes and obesity or overweight.
Topline: at the 36 mg dose, mean body-weight reduction was approximately 9.6% — smaller than the non-diabetic ATTAIN-1 population (Wharton 2025, ~11.2% at 36 mg)^[1], consistent with the established class pattern that GLP-1 receptor agonists produce less weight loss in T2D than in non-diabetic obesity. HbA1c reductions were clinically meaningful at all three doses. ATTAIN-2 supports the use of Foundayo (FDA-approved April 1, 2026)^[14] in T2D patients seeking an oral, non-injectable option.

SURMOUNT-OSA secondary outcomes (tirzepatide)

Published: February 2026, Nature Medicine^[5].
Design: pre-specified secondary analysis of the SURMOUNT-OSA Phase 3 trial originally published in NEJM October 2024^[4], reporting cardiometabolic endpoints (blood pressure, lipids, glycemia, hsCRP) on top of the apnea-hypopnea-index primary endpoint.
Topline: tirzepatide-treated participants showed reductions in systolic blood pressure, hsCRP, and improvements in lipid and glycemic markers that tracked with the AHI reduction reported in the primary readout. The secondary publication strengthens the clinical rationale for Zepbound’s OSA indication (FDA-approved December 20, 2024) and supports its growing footprint on Medicaid PDLs through 2026.

Retatrutide lipid & metabolite profiles

Published: May 14, 2026, J Clin Endocrinol Metab (PMID 42135195).
Design: exploratory profiling sub-study of the Phase 2 retatrutide obesity trial, with and without type 2 diabetes.
Topline: retatrutide-induced weight loss produced broad favorable shifts in lipid and metabolite profiles, consistent with the magnitude-of-weight-loss gradient documented in the original Phase 2 NEJM publication (Jastreboff 2023, PMID 37366315). This is not a Phase 3 primary readout — the registrational TRIUMPH program readout (NCT05929066 obesity-without-T2D, TRIUMPH-1) remains pending in 2026 with primary completion already hit on 2026-04-06^[15].

Trial registry status changes

Multiple registrational GLP-1 trials updated their ClinicalTrials.gov status in 2026 H1, primarily reflecting actual primary-completion dates being reached. All entries below were verified live against the ClinicalTrials.gov v2 API on 2026-05-23.

Note on TRIUMPH-1: the actual primary completion (2026-04-06) means the Eli Lilly retatrutide Phase 3 obesity readout in non-diabetic adults is now in the data-lock-to-publication window. A topline press release is the next likely milestone; the peer-reviewed NEJM publication typically lags by 6–12 months. We will add the TRIUMPH-1 readout to the Q3 2026 digest if it lands in the next window.

FDA approvals + label updates

The FDA Drugs@FDA structured submission record and DailyMed SetID timestamps were both pulled live on 2026-05-23^[14][12][13].

Foundayo (orforglipron) — new molecular entity

Approval date: April 1, 2026 (FDA NDA 220934, ORIG-1, submission status AP)^[14].
Indication: chronic weight management in adults with obesity (BMI ≥ 30 kg/m²) or overweight (BMI ≥ 27 kg/m²) with at least one weight-related comorbid condition. First oral small-molecule GLP-1 receptor agonist approved for chronic weight management; first non-peptide, non-injectable in the class.
Label SetID: 8ac446c5-feba-474f-a103-23facb9b5c62, published April 3, 2026^[11].
Pivotal evidence: ATTAIN-1 (Wharton 2025 NEJM)^[1] in non-diabetic adults and ATTAIN-2 (Horn 2026 Lancet)^[3] in adults with type 2 diabetes. Headline efficacy at the 36 mg dose was approximately 11.2% mean body-weight reduction in ATTAIN-1 and 9.6% in ATTAIN-2.

Wegovy (semaglutide) — label update + oral form available

Label updates (NDA 215256): Wegovy injection approved supplemental changes on January 29, 2026 (labeling), February 25, 2026 (labeling), and March 19, 2026 (efficacy)^[12]. The efficacy supplement is the structural signal of a new indication expansion or new outcomes-trial claim being added to the label.
Wegovy oral (NDA 218316): originally approved December 22, 2025; received labeling supplements on January 29, 2026, February 25, 2026, and March 19, 2026^[12]. The Wegovy DailyMed label (SetID ee06186f-2aa3-4990-a760-757579d8f77b) was re-published May 22, 2026 and now lists both injection, solutionand tablet dosage forms under a single SPL^[12] — the structural confirmation that Wegovy is now available as an oral tablet alongside the original subcutaneous form.

Zepbound (tirzepatide) — labeling refresh

Label updates (NDA 217806): labeling supplement 2 approved January 20, 2026; labeling supplement 42 approved February 25, 2026; manufacturing supplement 37 approved January 7, 2026^[13]. DailyMed SetID 487cd7e7-434c-4925-99fa-aa80b1cc776b last published May 6, 2026.
Zepbound retains its three FDA-approved indications — chronic weight management, moderate-to-severe obstructive sleep apnea (approved December 20, 2024), and heart failure with preserved ejection fraction in obesity (the SUMMIT trial)^[6]. The Q1–Q2 2026 supplements were scoped to labeling and manufacturing, not a new indication.

Null and negative readouts

Between January 1 and May 23, 2026, no GLP-1 / incretin Phase 3 trial was published with a primary-endpoint failure in the chronic-weight-management or T2D indication. No Phase 3 GLP-1 trial was terminated for futility or for safety in the window, per ClinicalTrials.gov v2 API verification of the trials listed in the registry table above^[15].

Two interpretive caveats:

1. ATTAIN-2 magnitude in T2D. The ~9.6% orforglipron weight loss in adults with T2D^[3] is meaningfully smaller than the ~11.2% in non-diabetic ATTAIN-1^[1]. This is mechanistically expected and is not a “failure,” but the gap is large enough that prescribers should set realistic expectations with T2D patients considering Foundayo.
2. Maintenance regain in ATTAIN-MAINTAIN.Participants randomized to placebo after the lead-in regained a clinically meaningful fraction of lost weight^[2]. This is consistent with the discontinuation biology of injectable GLP-1s (STEP-4, SURMOUNT-4) and is a structural reminder that GLP-1 therapy — oral or injectable — is chronic, not curative.

Pipeline tracker: what’s next

Major GLP-1 / incretin-multiagonist programs in late-stage development with expected next-readout dates. Status and primary-completion dates pulled live from ClinicalTrials.gov v2 API on 2026-05-23^[15].

FAQ

When was Foundayo approved?

The FDA approved Foundayo (orforglipron, NDA 220934 ORIG-1) on April 1, 2026 for chronic weight management in adults with obesity or overweight plus a weight-related comorbidity. Foundayo is the first oral small-molecule GLP-1 receptor agonist approved in the class — structurally distinct from oral semaglutide (Rybelsus / oral Wegovy), which is a peptide formulated with SNAC for oral absorption^[14][11].

What does ATTAIN-MAINTAIN tell us?

ATTAIN-MAINTAIN (NCT06584916, COMPLETED; Aronne 2026 Nat Med)^[2] is the first Phase 3b trial of an oral GLP-1 testing weight-maintenance vs placebo after a successful lead-in. Participants who stayed on orforglipron held their lead-in weight loss; participants randomized to placebo regained weight. This confirms that oral orforglipron behaves like injectable semaglutide and tirzepatide in the discontinuation paradigm — chronic therapy is required for chronic disease control.

What Phase 3 readouts published this quarter?

Four GLP-1 / incretin papers indexed in PubMed during the Q2 2026 window cited here: ATTAIN-2 (Lancet, Horn 2026)^[3], ATTAIN-MAINTAIN (Nat Med, Aronne 2026)^[2], SURMOUNT-OSA secondary cardiometabolic outcomes (Nat Med, Malhotra 2026)^[5], and the retatrutide lipid & metabolite profiles sub-analysis (J Clin Endocrinol Metab, May 14, 2026). The first three are primary or secondary outcomes from registrational Phase 3 trials; the fourth is an exploratory Phase 2 sub-study.

Did any GLP-1 trial fail this quarter?

No Phase 3 GLP-1 trial with a chronic-weight-management or T2D primary endpoint was published as a failure in the Q2 2026 window, and no listed Phase 3 GLP-1 trial was terminated for futility or safety in the ClinicalTrials.gov registry per the v2 API check on 2026-05-23^[15]. The clinically relevant nuance is the smaller magnitude of orforglipron weight loss in T2D (ATTAIN-2 ~9.6%) compared with non-diabetic obesity (ATTAIN-1 ~11.2%)^[1][3].

When is the next quarterly digest?

We publish a new quarterly digest at the end of each calendar quarter. The Q3 2026 digest will cover trial activity from May 24, 2026 through August 31, 2026 — the expected window for the TRIUMPH-1 (retatrutide) topline, the SYNCHRONIZE-1 (survodutide obesity) topline, and any further Wegovy or Zepbound label expansions.

If I want one of these drugs today, what are my options?

See our active reference pages: the full GLP-1 medication list for every FDA-approved option, where to buy Foundayo for the new oral approval, and the weight-loss injections guide for the injectable landscape. For the pipeline drugs in this digest (retatrutide, survodutide, MariTide, CagriSema), no FDA-approved consumer access exists yet.

Related research

Anchor reading for the broader GLP-1 landscape and each pipeline drug in this digest:

• Full GLP-1 medication reference list — every FDA-approved GLP-1, with dosing and the DailyMed SetID for each label.
• Foundayo (orforglipron) explainer — mechanism, ATTAIN-1 data, dosing.
• Weight-loss injections guide — how the injectable GLP-1s compare on effect size and tolerability.
• GLP-1 pipeline: survodutide, MariTide, ecnoglutide — deeper mechanism review of the agents in the tracker above.
• CagriSema REDEFINE trial results — the cagrilintide + semaglutide combination deep-dive.
• SELECT trial cardiovascular benefits in non-diabetics — the CV-outcomes evidence anchoring the Wegovy label.