# GLP-1 and related metabolic therapies

[Home](../README.md) · [Metabolic health and longevity](../WATCHLIST.md#metabolic-health) · [Calendar](../MILESTONES.md)

Tags: [Drugs and biologics](../BROWSE.md#drugs) · [During or after weight loss](../BROWSE.md#after-weight-loss)

## Current state

Oral VK2735’s SUNRISE program is announced, while registry recruitment remains pending with November starts; maintenance wording is corrected to daily oral dosing. Zenagamtide switching now records an actual start. A monthly-or-less-frequent Pfizer GLP-1 protocol adds early safety research.

Status: active. Initial research baseline checked 2026-09-12.

## Questions to follow

- Notable human trial results, new agents, oral or long-acting formulations, combinations, new indications, and regulatory developments.
- Include GLP-1 receptor agonists, dual or triple agonists, and closely related obesity combinations when relevant to this category.
- Track weight and fat reduction, maintenance, discontinuation or weight regain, cardiometabolic and other indication-specific outcomes, adverse effects, and tolerability.
- Record studied populations, doses as study descriptors, comparators, follow-up duration, and whether endpoints were prespecified. Avoid cross-trial efficacy rankings without accounting for design differences.
- For body composition, report absolute changes and the measurement method; distinguish lean mass from muscle function.

## Programs and next milestones

### Focused update — 2026-10-16

<span class="note-anchor" id="note-2026-10-14-oral-vk2735-sunrise-initiation"></span>

#### Viking announces SUNRISE initiation; first treatment remains unverified

**October 14 sponsor announcement, checked against October 16 registries.** Viking announces initiation of oral VK2735’s SUNRISE Phase 3 program. SUNRISE-1 (NCT07868835) and SUNRISE-2 (NCT07868939) each plan **560 adults**, without and with type 2 diabetes respectively, comparing daily **27.5, 35 or 55 mg** with placebo for **68 weeks**.

Both records still say **not yet recruiting**, with estimated starts now **November 2026**, replacing October 15/16 estimates. The announcement does not identify a first participant dosed; program initiation and confirmed treatment start remain separate. Primary completion estimates remain **July 2028** and **October 2028**, respectively. No Phase 3 results or U.S. approval.

**Separate maintenance-study correction:** The same October 14 release expressly corrects its October 6 announcement: maintenance options are **daily oral doses, monthly or every-other-week subcutaneous doses, or placebo**—the earlier “weekly oral” wording was erroneous. That approximately 195-person Part 2 study follows 21 weeks of initial weekly injections through week 33; the sponsor forecasts results in **2027**, without a quarter. This is a study plan, not demonstrated maintenance efficacy.

**Sources:** [Source 1](https://ir.vikingtherapeutics.com/2026-10-14-Viking-Therapeutics-Announces-Initiation-of-VK2735-Oral-Phase-3-Clinical-Program-in-Patients-with-Obesity); [Source 2](https://clinicaltrials.gov/study/NCT07868835); [Source 3](https://clinicaltrials.gov/study/NCT07868939); [Source 4](https://ir.vikingtherapeutics.com/2026-10-06-Viking-Therapeutics-Announces-Initiation-of-VK2735-Oral-Maintenance-Dosing-Clinical-Trial-in-Patients-with-Obesity).

<span class="note-anchor" id="note-2026-10-16-zenagamtide-switch-recruiting"></span>

#### Zenagamtide switching study now records recruitment and an actual start

**NCT07868354 / NN9490-8554, October 16 update.** Novo Nordisk’s planned **60-person Phase 1 open-label sequential study** now says **recruiting** and records **October 8, 2026 as actual start**, replacing the previously unverified estimated start.

Adults with overweight/obesity, with or without type 2 diabetes, switch from maintenance tirzepatide to weekly subcutaneous zenagamtide. Primary is the number of treatment-emergent adverse events from the first zenagamtide dose through **day 57**; pharmacokinetics are secondary. This is not concurrent treatment with both medicines or a randomized weight-loss comparison against continued tirzepatide.

No results or adverse-event rates are posted. Estimated primary/final completion remains **September 7, 2028**, without an announced publication date. Zenagamtide remains investigational in the U.S.; recruitment/start confirmation does not establish safety or approval.

**Sources:** [Source 1](https://clinicaltrials.gov/study/NCT07868354).

<span class="note-anchor" id="note-2026-10-15-pf08656795-monthly-protocol"></span>

#### Pfizer registers multiple-dose testing of a monthly-or-less-frequent GLP-1 candidate

**NCT07876518 / C6541002, first posted October 15.** Pfizer plans **150 adults aged 18–70**, BMI 25–40, in a randomized participant/investigator-masked, sponsor-open Phase 1 study of subcutaneous **PF-08656795 (MET-815i)** versus placebo. The arms specify **monthly or less frequent dosing**.

The sponsor’s earlier pipeline identifies MET-815i as a **GLP-1 receptor agonist prodrug of MET-097i**, the program now called berobenatide. This is a newly public multiple-dose protocol, not proof that the compound has only just entered human development.

Primary is adverse-event incidence through **12 weeks after the last dose**; pharmacokinetics are secondary. It does not supply an efficacy estimate, prove a dosing interval maintains weight loss, or establish long-term safety. The record is **not yet recruiting**, with **October 30, 2026 estimated start** and **November 16, 2028 estimated primary/final completion**. No results; U.S. use remains investigational.

**Sources:** [Source 1](https://clinicaltrials.gov/study/NCT07876518); [Source 2](https://cdn.pfizer.com/pfizercom/product-pipeline/Q4%202025%20Pipeline%20Update_vFinal3.pdf?VersionId=XSLcQ04JnYn3Py.PPsUP_5lAboV.fDPh); [Source 3](https://www.pfizer.com/science/drug-product-pipeline?developement_phase=phase_1).

**Remaining gaps:** Read current canonical scope, shared summaries, state and assigned topic notes. Bounded registry discovery covered September 5–October 16, 2026; prior October 13 findings were deduplicated. Full-topic successful-check dates remain unchanged.; Retrieved all 886 records across 9 pages of the bounded ClinicalTrials.gov query, plus 23 named records. Selected relevant new/changed protocols were appraised; downloading all records does not establish exhaustive safety/results review.; Europe PMC original-literature discovery failed with HTTP 503 for this topic. Targeted primary-source web searches supplied a partial fallback. Worldwide literature, regulators, international registries and complete original conference/podcast recordings remain incomplete.; SUNRISE sponsor initiation versus registry pending status was reconciled explicitly. Zenagamtide switching records were compared with October 13 snapshots. Other formulation/PK, body-composition and pediatric entries were screened selectively; routine registry edits were not promoted. Full international entrants, all holds/harms and original EASD discussion remain incomplete.

**Informal-source coverage:** Reopened original October 9 ENLIGHTEN-6 weekly thread: the saved appetite/skin/sleep account persists, without independent identity or causality verification; no repeat alert. SOLIS-1 direct thread retrieval again failed, so no status confirmation or retraction was inferred. Near-30% EloraTZP and future combination/titration/date claims remain unconfirmed. Wider EASD/Q&A/podcast source-chain review incomplete.

[Full coverage record](../updates/2026-10-16_scheduled_research_update.md).


### Focused update — 2026-10-13

<span class="note-anchor" id="note-2026-09-29-zupreme1-primary-publication"></span>

#### ZUPREME-1 publication adds exact doses, uncertainty and gastrointestinal event counts

**Published September 29; newly appraised October 13 — ZUPREME-1, NCT06662539.** This 42-week randomized placebo-controlled trial enrolled adults without type 2 diabetes. Of 493 randomized, 485 received treatment; mean BMI was 36.7 and 86% were White. Week-28 efficacy-estimand weight changes (95% CI) were:

| Weekly dose | Weight change |
| --- | --- |
| 1 mg | −7.9% (−9.0 to −6.7) |
| 2.5 mg | −7.9% (−9.0 to −6.7) |
| 5 mg | −9.8% (−10.9 to −8.6) |
| 7 mg | −9.3% (−10.5 to −8.2) |
| 9 mg | −9.4% (−10.5 to −8.3) |
| Placebo | −1.7% (−2.8 to −0.5) |

Nausea occurred in **79/404 active versus 5/81 placebo**; vomiting **12/404 versus 5/81**. No deaths were reported. Missing-data analyses assumed missing at random. These estimates do not establish superior tolerability to another drug or supply full safety tables. Petrelintide remains investigational; this is not the diabetes ZUPREME-2 readout.

**Sources:** [Source 1](https://pubmed.ncbi.nlm.nih.gov/42810355/); [Source 2](https://clinicaltrials.gov/study/NCT06662539).

<span class="note-anchor" id="note-2026-10-13-maritide-autoinjector"></span>

#### MariTide registers a home-autoinjector study

**NCT07871409, first posted October 13.** Amgen plans a Phase 3 open-label single-group study in **230 adults with overweight/obesity** receiving subcutaneous maridebart cafraglutide (MariTide). The co-primary endpoints are successful delivery of a full dose at home at **weeks 12, 16 and 20**, using attempted-injection and all-entering-home-phase denominators separately.

This tests delivery/usability; its Phase 3 label does not make it a randomized efficacy or cardiovascular-outcomes study. Safety and drug/device experience are additional considerations; no results are posted. Status is **not yet recruiting**. Start **October 28, 2026**, primary completion **June 16, 2027**, final completion **September 8, 2027** are registry estimates. MariTide remains investigational in the U.S.; no commercial device availability follows from registration.

**Sources:** [Source 1](https://clinicaltrials.gov/study/NCT07871409).

<span class="note-anchor" id="note-2026-09-25-selene3-lenbelintide-baseline"></span>

#### SELENE-3 studies lenbelintide added to an established incretin regimen

**Baseline program recovery, checked October 13 — SELENE-3, NCT07776509 / D8750C00011.** AstraZeneca's randomized double-blind Phase 3 trial plans **500 adults** with obesity/overweight and a related comorbidity, with or without type 2 diabetes. Weekly subcutaneous **lenbelintide (AZD6234)** or matching placebo is added to a stable background incretin medication.

Primary is percentage body-weight change at **68 weeks**. Eligibility requires a stable incretin dose for at least three months and weight change no more than 3% during three months before randomization. This is an add-on/plateau population, not a trial starting both drugs together in untreated participants; it does not establish efficacy or superiority to EloraTZP.

The sponsor page and September 25 registry say **recruiting**, actual start **August 24, 2026**, estimated primary/final completion **August 9, 2028**. No results. U.S. use is investigational. A Reddit recruitment lead led to this primary protocol; source recovery does not make August initiation new October news.

**Sources:** [Source 1](https://www.astrazenecaclinicaltrials.com/study/D8750C00011/); [Source 2](https://clinicaltrials.gov/study/NCT07776509).

**Remaining gaps:** Read current canonical scope, shared summaries/state and assigned topic notes. September 5–October 13 overlap preserves the September 12 full-review dates; October 6/9 entries were deduplicated. All pages of each bounded ClinicalTrials.gov query were downloaded, and named records plus selected relevant new/changed protocols were appraised. This is focused partial review, not a worldwide full literature/regulator/safety census; successful full-topic dates must remain unchanged.; Bounded query retrieved 804 records across 9 pages; incidental studies excluded. Named topic records refreshed: 20. Full older evidence, international registries, comprehensive harms and all original conference/podcast recordings remain gaps.

**Informal-source coverage:** Opened original October 9 ENLIGHTEN-6 weekly thread and permalink, selecting clearly unconfirmed symptoms. October 11/12 discussion contains speculation about slower titration, future EloraTZP/retatrutide combinations and access dates; none is a sponsor commitment. SOLIS-1 original direct fetch failed again; official record now active-not-recruiting with 940 actual participants, but that does not validate the saved anonymous symptoms. Prior near-30% EloraTZP rumor remains unconfirmed; no new matching source recovered. Full original EASD/Q&A/audio still incomplete.

[Full coverage record](../updates/2026-10-13_scheduled_research_update.md).


### Focused update — 2026-10-09

**Related evidence:** [COURAGE reports one-year lean-tissue preservation with low-dose trevogrumab](04_muscle.md#note-2026-10-01-courage52).

<span class="note-anchor" id="note-2026-10-07-zupreme2"></span>

#### Petrelintide reports phase 2b weight and HbA1c results in type 2 diabetes

**October 7 sponsor topline — ZUPREME-2, NCT06926842.** In U.S. adults with overweight/obesity and type 2 diabetes, mean baseline BMI was 36.3 and HbA1c 8.0%. The release reports 220 participants; the registry lists 221 actual participants, an unresolved denominator difference. Weekly subcutaneous petrelintide, an amylin analogue, was tested against placebo on background metformin with/without an SGLT2 inhibitor, diet and activity.

At week 28, efficacy-estimand weight loss was **7.4–9.2% versus 2.0%**. Maximum absolute HbA1c reduction was **0.65 percentage points**, versus a **0.23-point increase** with placebo; placebo-adjusted reductions ranged from **0.61 to 0.88 points**. No per-dose mapping, arm sizes, confidence intervals or exact p-values were released. Treatment-regimen estimates were called largely consistent without numerical values.

GI-related treatment discontinuation was **1.9% pooled active versus 1.7% placebo**; this is not the overall adverse-event rate. Detailed harms and longer-term outcomes remain pending. Petrelintide is investigational in the U.S. Full results are forecast for an undated conference.

**Sources:** [Primary source 1](https://www.globenewswire.com/de/news-release/2026/10/07/3376750/0/en/zealand-pharma-announces-positive-phase-2-zupreme-2-topline-results-for-amylin-analog-petrelintide-in-people-with-overweight-or-obesity-and-type-2-diabetes.html); [Primary source 2](https://clinicaltrials.gov/study/NCT06926842).

<span class="note-anchor" id="note-2026-10-07-petrelintide-phase3-start"></span>

#### Petrelintide phase 3 first treatment is confirmed

**Development status, not a new efficacy result.** Zealand's October 7 release confirms that the first participants have received treatment in its phase 3 program with Roche. Current protocols plan approximately 7,000 participants:

- **ZUPREME-3, NCT07843498:** 3,900 adults without type 2 diabetes; recruiting, actual start **September 30, 2026**. Estimated primary completion **December 21, 2028**; final **March 22, 2029**.
- **ZUPREME-4, NCT07843485:** 600 adults with type 2 diabetes; recruiting. September 30 remains an **estimated** start in this individual registry, so do not call it an independently verified actual dosing date. Estimated primary completion **October 20, 2028**; final **January 19, 2029**.
- **ZUPREME-5, NCT07843472:** 2,500 adults with established cardiovascular disease; recruiting, actual start **September 30, 2026**. Estimated primary completion **July 28, 2030**; final **October 6, 2030**.

Each compares weekly subcutaneous petrelintide with placebo and uses **64-week body-weight change** as primary. ZUPREME-5's cardiovascular population does not make this a cardiovascular-event-primary trial. Enrollment counts and completion dates are plans, not promised results. No posted results; U.S. use remains investigational.

**Sources:** [Primary source 1](https://www.globenewswire.com/de/news-release/2026/10/07/3376750/0/en/zealand-pharma-announces-positive-phase-2-zupreme-2-topline-results-for-amylin-analog-petrelintide-in-people-with-overweight-or-obesity-and-type-2-diabetes.html); [Primary source 2](https://clinicaltrials.gov/study/NCT07843498); [Primary source 3](https://clinicaltrials.gov/study/NCT07843485); [Primary source 4](https://clinicaltrials.gov/study/NCT07843472).

<span class="note-anchor" id="note-2026-10-09-oral-vk2735-sunrise"></span>

#### Oral VK2735 registers the SUNRISE phase 3 trials

**New registrations, first posted October 9 — not actual starts.** Viking's once-daily oral GLP-1/GIP agonist VK2735 enters registered phase 3 plans:

- **SUNRISE-1 / NCT07868835:** 560 adults without type 2 diabetes, obese or overweight with a weight-related comorbidity. Estimated start **October 15, 2026**; primary completion **July 2028**, final **August 2028**.
- **SUNRISE-2 / NCT07868939:** 560 adults with overweight/obesity and type 2 diabetes. Estimated start **October 16, 2026**; primary completion **October 2028**, final **December 2028**.

Both are randomized double-blind placebo-controlled trials of **27.5, 35 or 55 mg daily oral VK2735**, with percentage body-weight change at **68 weeks** primary. Both currently say **not yet recruiting**, have no results, and are distinct from the injectable VANQUISH program. VK2735 remains investigational; registration does not establish safety, efficacy, U.S. approval or actual initiation.

**Sources:** [Primary source 1](https://clinicaltrials.gov/study/NCT07868835); [Primary source 2](https://clinicaltrials.gov/study/NCT07868939).

<span class="note-anchor" id="note-2026-10-09-zenagamtide-switch"></span>

#### New trial studies tolerability when switching from tirzepatide to zenagamtide

**NCT07868354 / NN9490-8554, first posted October 9.** Novo Nordisk plans a phase 1 open-label sequential study in **60 adults with overweight/obesity, with or without type 2 diabetes**, taking maintenance tirzepatide. Participants switch from weekly subcutaneous tirzepatide to weekly subcutaneous zenagamtide.

The primary endpoint is the **number of treatment-emergent adverse events from the first zenagamtide dose through day 57**; pharmacokinetics are secondary. The design has no randomized continuing-tirzepatide comparator and does not test giving the two drugs together or establish which produces more weight loss. No results are posted.

Status remains **not yet recruiting** despite an **estimated October 8, 2026 start**, an elapsed plan rather than a verified start. Estimated primary/final completion is **September 7, 2028**; no public-result date is announced. Zenagamtide remains investigational in the U.S.

**Sources:** [Primary source 1](https://clinicaltrials.gov/study/NCT07868354).

**Remaining gaps:** Window: September 5–October 9, 2026, retaining the seven-day overlap from the last full successful check on September 12. October 6 findings were deduplicated.; 93 named NCT records across the ten topics and ten discovery queries downloaded successfully through the ClinicalTrials.gov public API. Download is not a claim that all fields/safety/results were exhaustively appraised.; Focused review only. Do not advance full successful-check timestamps or label incomplete remaining searches as no news.; GLP1 broad discovery returned 767 records; first 100 downloaded; selected relevant records screened; pagination and a worldwide entrant, safety/hold, formulation/approval census remain incomplete. Raw named records refreshed without treating routine edits as news. Root owns October 1 COURAGE; cross-link rather than duplicate. ZUPREME-2 exact dose mapping and complete harms/estimand tables unreleased.

**Informal-source coverage:** Oct8 original SOLIS-1 self-report and Oct9 comments retrieved through indexed original thread after direct fetch failure. Pfizer official study page independently matches GLP-1+dual amylin/calcitonin mechanism, but patient identity, allocation and causal attribution cannot be verified. Prior EloraTZP near-30% rumor remains unconfirmed; no new formal matching readout recovered. Full EASD/podcast audio and source-chain census remain incomplete.

[Full coverage record](../updates/2026-10-09_scheduled_research_update.md).


### Focused update — 2026-10-06

<span class="note-anchor" id="note-2026-09-29-triumph1"></span>

#### TRIUMPH-1 publication adds OSA and knee-pain substudies

**Source/event date: September 29, 2026. Evidence: peer-reviewed randomized phase 3 primary abstract.** TRIUMPH-1 (NCT05929066) randomized 2,339 adults with obesity without diabetes for 80 weeks. Treatment-regimen weight loss was 17.6%, 23.7% and 25.0% at 4, 9 and 12 mg versus 3.9% with placebo; adjusted differences for 9/12 mg were −19.8/−21.0 percentage points (both P<.001). These weight estimates were already in the sponsor baseline.

The publication adds 243-participant OSA and 574-participant knee-OA substudies. OSA intention-to-treat AHI changes were −22.8/−34.3/−32.1 versus −9.6 events/hour; adjusted 9/12-mg differences were −24.7/−22.5 (both P<.001). OA intention-to-treat pain differences were −1.4/−1.6 points (both P<.001). AHI is not cardiovascular benefit; pain is not cartilage repair. GI adverse events were most common. Full paper/supplements and confidence intervals were unavailable. The indexed hybrid-AHI paragraph has a sign inconsistency; it is not silently corrected. Retatrutide remains investigational. Next: full safety/supplement appraisal; no new approval date.

[Source 1](https://pubmed.ncbi.nlm.nih.gov/42814954/) · [Source 2](https://www.nejm.org/doi/10.1056/NEJMoa2604169)

**Coverage:** 2026-10-06: obesity GLP-1 trial October2026 retatrutide eloralintide AMPLIFY; 2026-10-06: NEJMoa2604169 PubMed; 2026-10-06: ClinicalTrials.gov LastUpdatePostDate September5–October6; interventional DRUG, obesity/GLP1; first50; 2026-10-06: Reddit EASD EloraTZP, original 1wu5875 claim and Oct5 1wyga38 repost

**Remaining gaps:** September5–October6 overlap; prioritize unpublished/recovered September29 TRIUMPH1 and newly registered metabolic trials. First50 recent drug-intervention records inspected; pagination remains. No worldwide safety/access/incretin census or new curve digitization.; Enicepatide NCT06628362 now COMPLETED in October6 record; endpoint timing discrepancy versus sponsor report was not fully reconciled.

**Informal-source coverage:** Read original u/Hopeful_Candle_9781 September30 thread and Oct5 r/Eloralintide repost; week31 near30%/future approvals remain unsupported/mixed-study claims. No new efficacy leak promoted. Full EASD Q&A/podcasts not reviewed.

**Related findings:**

- [Zenagamtide registers an 8,500-person cardiovascular-outcomes trial](07_cardiovascular.md#note-2026-10-06-ambience): see the study-specific population, endpoints and safety.
- [REMODEL reports null primary MRI comparisons alongside secondary kidney signals](17_kidney.md#note-2026-10-01-remodel): see the study-specific population, endpoints and safety.
- [New trial tests finerenone plus semaglutide in non-diabetic CKD](17_kidney.md#note-2026-09-30-finerenonesemaglutide): see the study-specific population, endpoints and safety.
- [ARO-INHBE adds a randomized MASH phase 2 plan](13_liver.md#note-2026-10-06-aroinhbe): see the study-specific population, endpoints and safety.
- [GLP-1 hair-symptom survey](19_hair_loss.md#note-2026-10-02-scopglp1): self-reported cross-sectional complaints do not establish a drug-caused adverse-event rate.

[Full coverage record](../updates/2026-10-06_scheduled_research_update.md).


### Focused update — 2026-10-02

#### EloraTZP improves weight and A1c more than tirzepatide, with more discontinuations

**Source/event date:** 2026-09-30. **Evidence:** Sponsor-reported randomized phase 2b conference results.

NCT06603571 randomized 367 adults with overweight/obesity and type 2 diabetes. At 48 weeks, eloralintide 9 mg plus tirzepatide 15 mg produced 23.3% mean weight loss versus 14.8% with tirzepatide 15 mg and 3.0% with placebo. These are efficacy-estimand estimates assuming continued treatment; placebo comparison was primary and tirzepatide comparison secondary. From mean A1c 8.1%, the slides report decreases of 2.91, 2.41 and 0.29 percentage points, respectively. Eloralintide alone at 6 mg reduced A1c 1.4 points in the rounded release table.

Adverse-event discontinuation was 27.0% in the high-dose combination versus 2.9% with tirzepatide and 16.7% with placebo; combination arms ranged 10.8–27.0%. Slides report nausea 49% and vomiting 24% for the high-dose combination. No confidence intervals were supplied in the release. The trial used separate injections; a co-formulated AMPLIFY phase 3 program with revised escalation is planned for Q4 2026, not verified started. The combination remains investigational. Diabetes-population weight results should not be ranked directly against trials excluding diabetes.

**Next milestone:** AMPLIFY phase 3 initiation in Q4 2026 — sponsor forecast; confirm registry and first dosing.

[Source 1](https://lilly.gcs-web.com/news-releases/news-release-details/lillys-eloratzp-combination-eloralintide-and-tirzepatide); [Source 2](https://lilly.gcs-web.com/static-files/aab1b091-48b3-430d-8ef5-1c69aae55318); [Source 3](https://clinicaltrials.gov/study/NCT06603571).

#### TRIUMPH-2 publication clarifies weight-loss estimates and safety

**Source/event date:** 2026-09-29. **Evidence:** Peer-reviewed primary abstract plus sponsor conference disclosure.

The Lancet report of TRIUMPH-2 (NCT05929079; 1,152 adults with obesity/overweight and type 2 diabetes) reports 80-week treatment-regimen weight loss of 11.9%, 16.8% and 18.8% with retatrutide 4, 9 and 12 mg versus 5.1% with placebo. For 12 mg, the placebo-adjusted difference was −13.8 percentage points (95% CI −15.8 to −11.8). This analysis includes treatment discontinuation; the earlier 20.8% headline is a different, efficacy estimand. Baseline A1c was 7.71%; 92% used oral glucose-lowering medication.

Permanent discontinuation for adverse events or death was 4%, 12% and 8% versus 5%. Gastrointestinal events, hypotension and altered skin sensation were more frequent with retatrutide. Six deaths occurred across retatrutide arms and one on placebo; investigators considered all unrelated. A small number of deaths cannot establish long-term mortality safety. Sponsor slides give efficacy-estimand A1c decreases of 1.41, 1.63 and 1.54 points versus 0.19; these should not be mixed with treatment-regimen weight estimates. Retatrutide remains investigational; no direct comparison with tirzepatide or semaglutide occurred in this trial.

**Next milestone:** Further comparative and cardiovascular-outcome trials remain separate; no approval date established here.

[Source 1](https://pubmed.ncbi.nlm.nih.gov/42810372/); [Source 2](https://investor.lilly.com/news-releases/news-release-details/lillys-triple-agonist-retatrutide-delivered-substantial-weight); [Source 3](https://lilly.gcs-web.com/static-files/aab1b091-48b3-430d-8ef5-1c69aae55318).

**Related findings:**

- [CBL-514 human MRI subgroup suggests visceral-fat reduction](06_localized_fat.md#cbl-514-human-mri-subgroup-suggests-visceral-fat-reduction).

**Coverage:** EASD September 29–October 2 EloraTZP TRIUMPH-2 new results; Lilly September30 analyst slides and NCT06603571 original registry; Eloralintide Reddit September30 combination results.

**Remaining gaps:** Selective conference and registry review, not a full worldwide incretin, insulin, safety or access census. Full TRIUMPH-2 paper and supplements were not retrieved; indexed primary abstract and sponsor tables were appraised. No curve digitization completed; T2D weight results must stay separate from the current non-diabetic weight-map population.

**Informal-source coverage:** September30 Reddit EloraTZP discussion repeats released data; a 29%-at-31-week claim was not corroborated and was not added as trial evidence. Original thread: https://www.reddit.com/r/mounjarouk/comments/1wu5875/eloralintide_tirzepatide_results_are_out_even/ . Full conference Q&A audio not appraised.

**Next update:** EloraTZP AMPLIFY phase 3 Q4 2026 sponsor forecast; confirm registration and first dosing. HRS-1596 timing remains estimated.

[Full coverage record](../updates/2026-10-02_scheduled_research_update.md).

### Focused update — 2026-09-29

#### HRS-1596 adds a planned once-weekly oral GLP-1/GIP program

**Source date:** 2026-09-29. **Evidence:** Sponsor development announcement and primary trial registry.

Hengrui and Novo announced development rights for an oral dual agonist intended for weekly dosing; human efficacy is not established. NCT07841860 / HRS-1596-101 was first posted September 25: Phase 1, randomized placebo-controlled dose escalation, 122 planned healthy or obese adults, one Chinese site. Primary endpoint is adverse-event incidence/severity through day 84.

**Limitations:** Registry remains NOT_YET_RECRUITING. September 2026 is an estimated start month, not proof of dosing. China permission to initiate research is not marketing approval.

**Safety:** No human safety results posted.

**U.S. status:** Investigational; no U.S. approval.

**Next milestone:** Registry estimates: primary completion December 2026; final completion May 2027. Global trial timing unannounced.

[Hengrui September 29 announcement](https://www.prnewswire.com/news-releases/hengrui-pharma-and-novo-enter-exclusive-license-agreement-for-once-weekly-oral-glp-1gip-dual-receptor-agonist-hrs-1596-302892378.html); [HRS-1596 primary registry](https://clinicaltrials.gov/study/NCT07841860).

#### Tirzepatide versus higher-dose semaglutide comparison depends on estimand

**Source date:** 2026-09-29. **Evidence:** Sponsor-reported conference indirect comparison.

A new comparison uses separate SURMOUNT-1 and STEP UP trials, not randomization between tirzepatide and semaglutide 7.2 mg. At 72 weeks, treatment-regimen differences favored tirzepatide 15 mg by 4.5 percentage points (95% credible interval −6.3 to −2.8) and 10 mg by 3.2 points (−5.0 to −1.4). Efficacy-estimand differences were −1.8 (−3.8 to 0.1) and −0.7 (−2.6 to 1.3), both compatible with no difference.

**Limitations:** Adjusted for sex, age, initial weight and A1c; residual cross-trial differences remain. Credible intervals are not confidence intervals. Do not present as a new head-to-head trial or add to randomized endpoint plots.

**Safety:** Sponsor describes comparable AE discontinuation without arm-level rates in this release; this does not establish equivalent overall safety.

**U.S. status:** Both branded injections have U.S. obesity indications; this analysis creates no new indication.

**Next milestone:** Full methods and independent appraisal; no new trial milestone announced.

[Lilly EASD indirect comparison](https://investor.lilly.com/news-releases/news-release-details/lillys-zepbound-tirzepatide-10-mg-and-15-mg-was-associated-more).

#### Orforglipron comparison extends to oral semaglutide 25 mg

**Source date:** 2026-09-29. **Evidence:** Sponsor-reported conference indirect comparison.

A covariate-adjusted indirect analysis compares orforglipron 17.2 mg against oral semaglutide 25 mg in adults with type 2 diabetes. Using ACHIEVE-3 and PIONEER PLUS, week-52 efficacy/trial-product estimands favored orforglipron by 1.5 percentage points of weight change (95% CI −2.7 to −0.2) and 0.3 percentage points of HbA1c (−0.6 to −0.1).

**Limitations:** This is not the ACHIEVE-3 randomized comparison against oral semaglutide 14 mg. Cross-study assumptions and treatment-adherent estimands limit causal interpretation.

**Safety:** No new comparative numerical adverse-event analysis in the announcement.

**U.S. status:** Foundayo is U.S.-approved for adult weight management; diabetes remains an investigational indication in the reviewed release. Oral semaglutide 25 mg is not U.S.-approved for diabetes in that release.

**Next milestone:** Full comparative methods and indication-specific regulatory updates; no new decision date.

[Lilly September 29 oral-drug comparison](https://investor.lilly.com/news-releases/news-release-details/lillys-foundayo-orforglipron-172-mg-showed-greater-weight-loss).

#### Weekly insulin: date correction and access context

**Correction verified September 29:** Onswik was approved **September 23**, and announced September 24. The earlier entry used the announcement date as the approval date; its stable event key is preserved. This is a correction, not another approval.

Awiqli was the first U.S. weekly basal insulin, approved March 26 and announced available August 11. Onswik is the second; as checked September 29 the sponsor still forecasts availability in coming months. Neither replaces mealtime insulin. Medicare $35-or-less monthly insulin cap applies only when the particular Part D plan covers the product; no nationwide or individual-plan coverage is established here.

[FDA original Awiqli approval package](https://www.accessdata.fda.gov/drugsatfda_docs/nda/2026/761326Orig2s000Approv.pdf); [Novo U.S. homepage links August 11 launch release](https://www.novonordisk-us.com/); [Onswik HCP launch FAQ](https://onswik.lilly.com/); [Awiqli conditional Medicare coverage](https://www.awiqli.com/savings-and-support.html); [Medicare covered-insulin rules](https://www.medicare.gov/coverage/insulin).

**Related findings:**

- [Claims-data analysis compares semaglutide escalation with tirzepatide switching](07_cardiovascular.md#programs-and-next-milestones).
- [Singapore adds a Wegovy indication for noncirrhotic MASH](13_liver.md#programs-and-next-milestones).

**Coverage:** September 5–29 overlap with September 27–29 focus: EASD sponsor announcements, new oral program discovery, HRS-1596 and enicepatide registries, weekly insulin correction/access.

**Remaining gaps:** Not a complete worldwide incretin/diabetes registry or safety census. EASD SPOTLIGHT original abstract not retrieved; Reddit numbers not treated as established. Enicepatide registry still lists week-36 co-primary endpoints versus week-48 sponsor topline.

**Informal-source coverage:** Read September 28 eloralintide discussion and September 29 SPOTLIGHT Reddit post; claims may mix studies/populations. No original-data leak selected. https://www.reddit.com/r/Eloralintide/comments/1wsjbhw/easd_abstract_about_eloralintide_and_tirzepatide/ ; https://www.reddit.com/r/NovoNordisk_Stock/comments/1wtdtla/novo_presents_china_realworld_study_of_160000/ . Full podcast recordings not reviewed.

**Next update:** September 30 BELIEVE, eloraTZP and TRIUMPH-2 presentations; HRS-1596 registry primary completion December 2026 (estimate), without confirmed first dosing.

[Full coverage record](../updates/2026-09-29_scheduled_research_update.md).

### Focused update — 2026-09-27

#### Enicepatide reports Phase 2 diabetes and weight-loss results

**Source date:** 2026-09-22. **Event date:** 2026-09-22. **Evidence:** Sponsor topline announcement.

Roche reports glycemic and weight reductions in 447 adults with type 2 diabetes and overweight/obesity. CT-388-104 / NCT06628362: randomized, double-blind, placebo-controlled. At 24 mg, reported week-48 HbA1c change was −2.65 percentage points from 8.1%; weight change −15.5%.

**Limitations:** Placebo magnitudes, intervals, estimand and arm denominators withheld. June 24 registry still specifies week-36 co-primary endpoints, whereas the release calls them week-48: unresolved source discrepancy. On-treatment normal HbA1c is not diabetes remission.

**Safety:** AE discontinuation: 2.0% pooled enicepatide versus 0% placebo; predominantly mild/moderate gastrointestinal events. Detailed serious-event table unavailable.

**U.S. status:** Investigational; no U.S. approval.

**Next milestone:** Phase 3 glycemic-control program and cardiovascular-outcomes trials planned H1 2027; ENITH-1/2 obesity studies ongoing.

[Roche September 22 topline](https://www.roche.com/media/releases/med-cor-2026-09-22); [CT-388-104 original registry](https://clinicaltrials.gov/study/NCT06628362).

#### FDA approves once-weekly Onswik insulin for type 2 diabetes

**Source date:** 2026-09-24. **Event date:** 2026-09-24. **Evidence:** FDA regulatory action.

Onswik (insulin efsitora alfa-gobe) adds a weekly basal-insulin option for adults with type 2 diabetes. Four randomized open-label active-controlled QWINT trials in over 3,400 adults found noninferior HbA1c reductions versus daily glargine or degludec. This is insulin, not an incretin or weight-loss medicine.

**Limitations:** Approval does not establish superior complication prevention or immediate pharmacy stock. FDA identifies it as the second approved weekly insulin.

**Safety:** Hypoglycemia, dosing errors/overdose and weight gain matter. Not recommended for type 1 diabetes because of increased severe-hypoglycemia risk.

**U.S. status:** FDA-approved for adult type 2 diabetes with diet and exercise.

**Next milestone:** Lilly forecasts U.S. KwikPen availability in coming months; exact launch unannounced.

[FDA once-weekly insulin approval](https://www.fda.gov/drugs/news-events-human-drugs/fda-approves-once-weekly-insulin-type-2-diabetes-mellitus); [Lilly approval and launch forecast](https://investor.lilly.com/news-releases/news-release-details/us-food-and-drug-administration-fda-approves-lillys-onswiktm).

#### BGM0504 Phase 2 obesity trial gains a peer-reviewed report

**Source date:** 2026-09-17. **Event date:** 2026-09-17. **Evidence:** Peer-reviewed randomized trial; primary abstract reviewed.

A 120-participant Chinese trial reports substantial 24-week weight loss with the dual GLP-1/GIP agonist. NCT06973681 / CTR20233198: randomized 1:1:1:1 to 5, 10, 15 mg or placebo. Mean weight changes −10.68%, −16.07%, −18.33% and +0.13%, respectively (all active comparisons p<0.0001).

**Limitations:** Previously disclosed results now published; not a new trial start. Abstract lacks intervals/estimand. Trial completed September 2024; ClinicalTrials.gov first posted May 2025, after completion. Chinese registry registration timing not verified.

**Safety:** TEAEs: 96.7%, 93.5%, 100%, 86.7%; gastrointestinal effects common. One SAE in 10-mg arm; no TEAE-related withdrawal. Arm denominators require full paper rather than inferred equal n.

**U.S. status:** Investigational in U.S.

**Next milestone:** Longer Phase 3 results and full-paper appraisal; no next verified public date.

[BGM0504 primary PubMed abstract](https://pubmed.ncbi.nlm.nih.gov/42755112/); [Original journal article](https://doi.org/10.1111/dom.71193); [BGM0504 registry](https://clinicaltrials.gov/study/NCT06973681).

**Related findings:**

- [BELIEVE abstract describes six months after treatment withdrawal](04_muscle.md#programs-and-next-milestones).

**Coverage:** September 5–27 overlap, prioritizing September 23–27: Roche CT-388 diabetes, BGM0504 publication, insulin approval, EASD official schedule and new human-program discovery. Deduplicated VK2735/CagriSema announcements.

**Remaining gaps:** CT-388 registry/release endpoint timing unresolved; placebo effects and estimand absent. BGM0504 full paper inaccessible. Not a complete worldwide incretin registry/safety census.

**Informal-source coverage:** Searched Reddit enicepatide/retatrutide and conference forecasts. September 26 self-reported trial participant thread mainly anecdotes and an unverified upcoming-diabetes-presentation claim; no additional efficacy rumor promoted. Original: https://www.reddit.com/r/antidietglp1/comments/1wqerf2/week_one/ . Roche public EASD agenda checked; no assumption that every enicepatide talk is new diabetes readout.

**Next update:** EASD September 28–October 2; eloraTZP September 30. Enicepatide diabetes and cardiovascular-outcomes Phase 3 starts forecast H1 2027; Onswik U.S. launch forecast in coming months.

[Full coverage record](../updates/2026-09-27_scheduled_research_update.md).

### Focused update — 2026-09-22

#### VK2735 reports results for less frequent maintenance dosing

**Source date:** 2026-09-22. **Event date:** 2026-09-22. **Evidence:** Sponsor topline announcement.

Following 21 weeks of weekly induction, every-other-week and monthly injections preserved more of the initial weight loss over 12 weeks than withdrawal to placebo. VK2735-102 was a randomized, double-blind study in approximately 180 adults with obesity. Combined every-other-week efficacy arms (n=37) retained 90% of prior loss; monthly (n=65) retained 85%; placebo (n=27), 61%. A continued-weekly 17.5 mg subgroup (n=13) lost 21.7% from baseline by week 33.

**Limitations:** Sponsor-only exploratory weight endpoint, small selected maintenance cohorts and short follow-up; retention is not percentage body-weight loss. Highest monthly arm excluded an outlier; including it changes that arm's retention from 85% to 99%. No confidence intervals or verified NCT match recovered.

**Safety:** Maintenance TEAEs: 14/37 every-other-week, 32/66 monthly, 14/27 placebo; AE discontinuations 1/37, 1/66, 0/27. Induction-selected tolerability cannot establish comparative long-term safety.

**U.S. status:** Investigational for this use; no new U.S. approval.

**Next milestone:** Oral maintenance part 2 planned; date unverified. Prior Q3 maintenance forecast fulfilled.

[Viking September 22 maintenance topline](https://ir.vikingtherapeutics.com/2026-09-22-Viking-Therapeutics-Announces-Positive-Topline-Results-from-Maintenance-Study-of-GLP-1-GIP-Agonist-VK2735-Demonstrating-the-Promise-of-Multiple-Maintenance-Dosing-Regimens).

#### Lower-dose CagriSema reports head-to-head diabetes results

**Source date:** 2026-09-21. **Event date:** 2026-09-21. **Evidence:** Sponsor topline announcement.

REIMAGINE 5 reported greater weight reduction and noninferior HbA1c reduction with CagriSema 1.0/1.0 mg versus tirzepatide 5 mg. Phase 3 randomized open-label trial NCT06534411, 1,023 actual participants with type 2 diabetes and BMI ≥30 on metformin, an SGLT2 inhibitor, or both. At 60 weeks, efficacy-estimand weight change was −12.42% versus −9.12%; HbA1c change −1.71 versus −1.67 percentage points. Mean baseline HbA1c 8.1%, BMI 37.2.

**Limitations:** Low-dose comparison, not versus tirzepatide 15 mg. No treatment-policy estimates, CIs or noninferiority margin recovered; no clinical-complication outcome. Do not supersede the different REDEFINE 4 comparison.

**Safety:** Sponsor characterized tolerability as consistent with previous trials; detailed arm-level AE/SAE rates not provided in retrieved release or slide.

**U.S. status:** Investigational for this use; no new U.S. approval.

**Next milestone:** CagriSema U.S. weight-management decision forecast Q4 2026; REDEFINE 3 CVOT forecast H2 2027.

[Novo September 21 release](https://www.globenewswire.com/de/news-release/2026/09/21/3365319/0/en/novo-s-cagrisema-delivers-superior-weight-loss-versus-tirzepatide-in-reimagine-5-trial.html); [Novo Diabetes CMD, slide 9](https://www.novonordisk.com/content/dam/nncorp/global/en/investors/pdfs/capital-markets-day/2026/Diabetes-presentation.pdf); [NCT06534411 registry](https://clinicaltrials.gov/study/NCT06534411).

#### REDEFINE 9 reports weight loss with lower-dose CagriSema

**Source date:** 2026-09-21. **Event date:** 2026-09-21. **Evidence:** Sponsor topline announcement.

The lower-dose regimen reported approximately 21% weight reduction over 68 weeks in adults without diabetes. Phase 3 randomized quadruple-masked NCT06388187, 300 actual participants with obesity or overweight plus a complication, excluding diabetes. Efficacy-estimand reduction: 20.95% at 1.0/1.0 mg; 20.75% at 1.7/1.7 mg. Displayed placebo change −2%. Protocol allowed flexible dosing.

**Limitations:** Sponsor slides/topline only. Arm sizes, confidence intervals, treatment-policy estimates and ≥5% co-primary counts unavailable. Not evidence that lower doses are superior to higher doses across different trials.

**Safety:** Discontinuation for any AE: 4.9% at 1.0/1.0 mg, 2.9% at 1.7/1.7 mg, 4.9% placebo. Complete AE/SAE frequencies not released.

**U.S. status:** Investigational for this use; no new U.S. approval.

**Next milestone:** U.S. decision forecast Q4 2026. REDEFINE 11 readout now forecast Q1 2027; high-dose program readout H1 2028.

[Novo September 21 release](https://www.globenewswire.com/de/news-release/2026/09/21/3365319/0/en/novo-s-cagrisema-delivers-superior-weight-loss-versus-tirzepatide-in-reimagine-5-trial.html); [Novo Obesity CMD, slide 9](https://www.novonordisk.com/content/dam/nncorp/global/en/investors/pdfs/capital-markets-day/2026/obesity-presentation-cmd-2026.pdf); [NCT06388187 registry](https://clinicaltrials.gov/study/NCT06388187).

**Related findings:**

- [CagriSema reports a Phase 2 painful-neuropathy signal](16_pain.md#programs-and-next-milestones).
- [Novo plans first human study of a PCSK9/GLP-1 combination](07_cardiovascular.md#programs-and-next-milestones).
- [New liver-development plans target MASH and alcohol-related disease](13_liver.md#programs-and-next-milestones).

**Coverage:** September 5–22 overlap; Viking maintenance, Novo CMD/readouts, EASD timing, human-development announcements and fresh registries. Priority September 18–22.

**Remaining gaps:** Full tables/CIs and treatment-policy estimands for new CagriSema trials unavailable. VK2735-102 NCT identifier not matched; exact registry phase not asserted. Not a complete global registry/conference census; no full webcast audio review.

**Informal-source coverage:** Targeted Reddit and management-talk searches; today's VK2735 discussion mainly repeats the official release. Novo investor posts do not establish unpublished readouts. CagriSema neuropathy cross-reported once in pain.

[Full coverage record](../updates/2026-09-22_scheduled_research_update.md).

**Next update:** **September 28–October 2:** EASD; **September 30:** eloraTZP presentation. Further maintenance and CagriSema full-data follow-up dates remain study-specific.

### Focused update — 2026-09-18

#### Non-incretin CRB-913 reports phase 1b weight-loss data

**Source date:** 2026-09-14. **Evidence:** Sponsor topline.

The oral peripheral CB1 inverse agonist adds a non-incretin obesity program to the broader metabolic watch. CANYON-1, NCT07310901, randomized 254 U.S. adults with obesity without diabetes. After 12 weeks of treatment, efficacy-estimand weight loss was 2.8%, 3.3% and 5.0% across active doses versus 0.0% with placebo (all p < .0001). The highest-dose arm included 62 participants; placebo included 66. Four weeks of follow-up followed treatment. The registry retains an older May 29 snapshot, with estimated enrollment of 252 and no posted results; preserve the later sponsor-reported analysis population.

**Limitations:** Short phase 1b study, no uncertainty intervals or long-term outcomes; sponsor GLP-1 comparisons are cross-trial, not head-to-head. Do not label CRB-913 an incretin or add it to hormone-mimetic plots without explicit scope change.

**Safety:** Adverse-event discontinuations ranged from 3.1% to 13.1%; irritability affected 6.2%–9.7% across active doses versus 0% with placebo. No serious/severe psychiatric event or suicidality reported. Gastrointestinal symptoms occurred; long-term neuropsychiatric safety remains unestablished.

**U.S. status:** Investigational.

**Next milestone:** A detailed presentation is scheduled for ObesityWeek, November 14–17, 2026. The sponsor targets a phase 2 start in the first half of 2027.

[Corbus September14 release](https://ir.corbuspharma.com/news-events/press-releases/detail/478/corbus-pharmaceuticals-announces-positive-topline-data-from-canyon-1-study-of-daily-oral-crb-913-for-the-treatment-of-obesity); [CANYON-1 registry](https://clinicaltrials.gov/study/NCT07310901).

#### Eloralintide plus tirzepatide phase 2 presentation scheduled

**Source date:** 2026-09-15. **Evidence:** Official sponsor conference schedule.

Lilly specifies the upcoming eloraTZP phase 2 disclosure at EASD. Eloralintide plus tirzepatide results in adults with overweight or obesity and type 2 diabetes are scheduled for September 30, 16:30–17:30 CEST. Retatrutide/TRIUMPH-2 is scheduled for September 30, 08:30–09:30 CEST; Foundayo/ACHIEVE is scheduled for October 1, 08:30–09:15 CEST.

**Limitations:** The announcement contains no new numerical eloraTZP efficacy or safety results. ACHIEVE-4 estimates repeat April 16 data and should not be presented as new September findings or proof of superiority: four-component MACE HR 0.84 (95% CI 0.59–1.20); three-component MACE HR 0.77 (95% CI 0.52–1.13).

**Safety:** The new combination safety presentation is pending.

**U.S. status:** The combination is investigational; approved indications for its components do not establish approval of the combination.

**Next milestone:** The eloraTZP symposium is scheduled for September 30, 2026.

[Lilly EASD announcement](https://investor.lilly.com/news-releases/news-release-details/lilly-present-new-data-foundayo-retatrutide-and-eloratzp-easd).

**Related findings:**

- [Completed finerenone–semaglutide combination study appears in registry](17_kidney.md#programs-and-next-milestones): A newly posted human trial will be followed for results; it is not a new trial launch.
- [Resistance-training study during tirzepatide treatment is listed as recruiting](04_muscle.md#programs-and-next-milestones): A randomized study will measure whether resistance training preserves contractile thigh muscle during tirzepatide treatment.
- [Small sponsor studies explore skin care after medication-associated weight loss](20_skin_aging.md#programs-and-next-milestones): Allergan reports early skin-quality improvements in people taking weight-loss medicines, from two very small single-center studies.

**Coverage:** CRB-913 new mechanism and sponsor results; Lilly EASD schedule, STEP Young repeat; Viking maintenance and major pipeline discovery queries. This is a focused review, not a complete re-review of every program.

**Remaining gaps:** Not every global incretin registry or safety source was refreshed. The Lilly page returned a 403 error, but its indexed primary announcement and PDF were readable. The original audio from Viking’s September 14 conference appearance was not reviewed.

**Informal-source coverage:** Targeted Reddit and podcast searches largely returned older results and investor predictions. Viking September 14 third-party transcript found, but original conference recording not reviewed; no new result leak verified.

[Full coverage record](../updates/2026-09-18_scheduled_research_update.md).

### Focused update — 2026-09-14

<span class="note-anchor" id="note-2026-09-07-pediatric-semaglutide-trial-reports-positive-topline"></span>**2026-09-07 — Pediatric semaglutide trial reports positive topline.** Novo’s September 7 release reports that STEP Young met its 68-week BMI primary endpoint in 165 children aged 6 to under 12 with obesity. Under the trial-product estimand, 40.4% versus 0% crossed below the age- and sex-specific obesity threshold. That is a secondary classification endpoint, not percentage weight loss. Numerical primary-endpoint effects, intervals and detailed adverse-event tables were not released; the sponsor reported no new safety or growth/puberty concerns. **No new approval for this age group is established by these results.** Full data are scheduled for ObesityWeek, November 14–17. [Sponsor topline](https://www.novonordisk.com/news-and-media/news-and-ir-materials/news-details.html?id=916600). [NCT05726227](https://clinicaltrials.gov/study/NCT05726227) includes children and adolescents and still lists estimated enrollment of 210; that wider registry count must not replace the reported younger-cohort denominator.

**Coverage:** STEP Young phase 3 topline, September 7; newly added within overlap window. STEP Young numerical primary BMI effect and detailed adverse events not in topline; pediatric cohort differs from registry-wide planned enrollment. No new VK2735 maintenance result in current sponsor releases. Informal search surfaced reposted STEP Young data and speculative conference expectations, without a distinct verifiable new rumor. This was a focused refresh, not a complete re-review of every program.

Checked sources: [Source 1](https://www.novonordisk.com/news-and-media/news-and-ir-materials/news-details.html?id=916600); [Source 2](https://clinicaltrials.gov/study/NCT05726227); [Source 3](https://ir.vikingtherapeutics.com/press-releases); [Source 4](https://investor.lilly.com/); [Source 5](https://www.novonordisk.com/investors/financial-results.html).

**Next update:** **September 28–October 2:** EASD conference opportunity. CagriSema FDA decision expected late 2026; retatrutide filing targeted Q1 2027 (sponsor windows).

### Tracked programs and current evidence

#### Initial brief — 2026-09-12

**Current position:** this category now includes approved oral obesity treatments, broader disease indications, and several late-stage combinations. The important question is increasingly whether a treatment improves durable health outcomes, tolerability, and maintenance as well as weight loss.

**Already available in the U.S.** Oral Wegovy (semaglutide 25 mg) was approved December 22, 2025 and launched January 2026; injectable Wegovy HD 7.2 mg was approved March 19, 2026. Foundayo (orforglipron), a small-molecule oral GLP-1 agonist, was approved April 1, 2026 for adult weight management. Its diabetes application had been submitted by August 2026; that is a separate indication. [Novo oral approval](https://www.novonordisk.com/news-and-media/news-and-ir-materials/news-details.html?id=916472), [FDA higher-dose approval](https://www.fda.gov/news-events/press-announcements/fda-approves-fourth-product-under-national-priority-voucher-program-higher-dose-semaglutide), [FDA Foundayo approval letter](https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2026/220934Orig1s000ltr.pdf), [Lilly August update](https://investor.lilly.com/news-releases/news-release-details/lilly-reports-second-quarter-2026-financial-results-raises-full).

Beyond obesity, Zepbound has an approved indication for moderate-to-severe obstructive sleep apnea in adults with obesity. Wegovy injection has accelerated approval for MASH with moderate-to-advanced fibrosis: biopsy improvements supported approval, while the trial continues to test clinical liver outcomes. These are population-specific indications. [FDA sleep-apnea approval](https://www.fda.gov/news-events/press-announcements/fda-approves-first-medication-obstructive-sleep-apnea), [FDA MASH evidence](https://www.fda.gov/drugs/news-events-human-drugs/fda-approves-treatment-serious-liver-disease-known-mash).

**Worldwide context:** mazdutide, a GLP-1/glucagon dual agonist, gained Chinese approval for weight management in June 2025 and diabetes in September 2025. Chinese approval does not establish U.S. availability. [Innovent weight-management announcement](https://en.innoventbio.com/InvestorsAndMedia/PressReleaseDetail?key=546), [diabetes announcement](https://en.innoventbio.com/InvestorsAndMedia/PressReleaseDetail?key=556).

**Six priority investigational programs:**

- **Retatrutide, GLP-1/GIP/glucagon triple agonist:** TRIUMPH-1 ([NCT05929066](https://clinicaltrials.gov/study/NCT05929066)) sponsor topline showed 28.3% weight loss versus 2.2% placebo at 80 weeks with 12 mg under the efficacy estimand; the treatment-regimen estimates were 25.0% versus 3.9%. Gastrointestinal effects and dysesthesia matter; adverse-event discontinuation was 11.3% versus 4.9% at that dose. July TRIUMPH-2/3 readouts extended the evidence to diabetes and established cardiovascular disease; their cardiovascular-event analyses did **not** establish event reduction. [May topline](https://investor.lilly.com/news-releases/news-release-details/lillys-triple-agonist-retatrutide-delivered-powerful-weight-loss), [July topline; NCT05929079/NCT05882045](https://investor.lilly.com/news-releases/news-release-details/lillys-triple-agonist-retatrutide-successful-two-additional).
- **CagriSema, semaglutide plus cagrilintide:** submitted to FDA after REDEFINE-1/2. The 809-person, open-label REDEFINE-4 comparison failed its noninferiority endpoint versus tirzepatide: 20.2% versus 23.6% weight loss at 84 weeks regardless of adherence. Substantial weight loss therefore coexists with a negative comparative result. [Sponsor February readout](https://www.novonordisk.com/news-and-media/news-and-ir-materials/news-details.html?id=916501), [published REDEFINE-1; NCT05567796](https://www.nejm.org/doi/10.1056/NEJMoa2502081).
- **Zenagamtide (formerly amycretin), single-molecule GLP-1/amylin agonist:** injectable obesity development has reached phase 3. A randomized 262-person diabetes phase 2 study reported up to 14.6% weight loss at 36 weeks; its primary endpoint was HbA1c, with weight secondary. Oral development adds a separate formulation opportunity. [June results](https://www.novonordisk.com/news-and-media/news-and-ir-materials/news-details.html?id=916559), [August program update](https://www.novonordisk.com/content/dam/nncorp/global/en/investors/pdfs/financial-results/2026/Q2-2026-Full%20presentation.pdf).
- **VK2735, GLP-1/GIP agonist:** weekly injectable VANQUISH-1/2 phase 3 trials are fully enrolled, testing weight change over 78 weeks. Oral phase 2 supports further development, but gastrointestinal tolerability remains relevant. [July program update](https://ir.vikingtherapeutics.com/2026-07-29-Viking-Therapeutics-Reports-Second-Quarter-2026-Financial-Results-and-Provides-Corporate-Update), [oral phase 2 conference data](https://vikingtherapeutics.com/wp-content/uploads/2026/05/Treatment-with-Oral-VK2735-Results-in-Significant-Weight-Loss-The-Randomized-Placebo-Controlled-Dose-Finding-VENTURE-Oral-Study.pdf).
- **MariTide, GLP-1 agonist/GIP-receptor antagonist:** phase 3 MARITIME includes obesity, cardiovascular events, heart failure, sleep apnea, and switching/maintenance. Monthly and less frequent schedules are being tested; convenience and maintained benefit are central questions. [Amgen August update](https://investors.amgen.com/news-releases/news-release-details/amgen-reports-second-quarter-2026-financial-results/).
- **Eloralintide, selective amylin agonist:** phase 2 reported up to 20.1% versus 0.4% placebo weight loss at 48 weeks under an efficacy estimand; higher doses had more gastrointestinal symptoms/fatigue. Phase 3 includes obesity and incretin add-on treatment. [Phase 2 report](https://lilly.gcs-web.com/news-releases/news-release-details/lillys-selective-amylin-agonist-eloralintide-demonstrated), [2026 trial initiation filing](https://www.sec.gov/Archives/edgar/data/59478/000005947826000045/lly-20260331.htm).

#### Expected next updates

- **Announced:** EASD, September 28–October 2, 2026, is a conference opportunity, not a guaranteed drug readout. [Official dates](https://www.easd.org/uploads/EASD2026_Guidance_Abstract-Submission.pdf).
- **Sponsor windows:** VK2735 maintenance data Q3 2026 and oral phase 3 initiation Q4 2026; CagriSema FDA decision anticipated late 2026, REDEFINE-11 readout H1 2027; retatrutide U.S. filing Q1 2027. Sources are the program updates above. Filing and trial initiation are not approval or efficacy results.
- **No reliable near-term readout date verified:** MariTide and zenagamtide pivotal efficacy, or eloralintide phase 3 efficacy. Monitor registry changes and conference abstracts.

**Interpretation:** these percentages are not a cross-trial ranking. Populations, duration, adherence assumptions, and comparators differ. This is a selective baseline; additional indications and smaller early programs remain within the watch scope.

### Cross-links

- [Muscle preservation](04_muscle.md)
- [Localized fat removal, visceral fat and combinations](06_localized_fat.md)
- [Cardiovascular prevention](07_cardiovascular.md)

## Rumors and informal signals

<span class="note-anchor" id="note-2026-10-09-enlighten6-informal-week9"></span>

#### Anonymous ENLIGHTEN-6 report describes sleep disruption and skin sensitivity

**Informal statement — unconfirmed.** In the October 9 r/Eloralintide weekly thread, **u/NoMoreFatShame** describes their ninth treatment week in ENLIGHTEN-6: more waking/tossing and turning, recurrent skin sensitivity described as allodynia, constipation and difficulty eating because of strong appetite suppression. The commenter guesses that the new medication box might contain a higher dose; they do not know the blinded dose/allocation.

The original thread shows the comment, although fetching its direct permalink separately failed; no study participation, investigator assessment or attribution to active drug is independently verified. This is one person's account, not an incidence rate, comparative safety estimate, established adverse reaction or new efficacy readout. Earlier appetite anecdotes are not independent corroboration. No inference about which specific drug/dose caused symptoms or treatment advice follows. The study's aggregate safety and discontinuation tables remain the appropriate next evidence.

**Sources:** [Source 1](https://www.reddit.com/r/Eloralintide/comments/1x1if30/hows_your_trial_going_weekly_update_post_let_us/); [Source 2](https://www.reddit.com/r/Eloralintide/comments/1x1if30/comment/peuke7q/); [Source 3](https://trials.lilly.com/en-US/trial/664336).

### October 9 informal-source check

<span class="note-anchor" id="note-2026-10-08-solis1-informal"></span>

#### Anonymous SOLIS-1 participant describes vomiting, drowsiness and tremor after dose escalation

**Unconfirmed informal safety signal, October 8 original post.** A person claiming SOLIS-1 participation describes nausea/vomiting, marked midday drowsiness, evening chills/tremor and excess fullness after dose escalation. Pfizer's official page independently describes NCT07575932 as a trial of a GLP-1 agonist plus a dual amylin/calcitonin agonist, alone/together or placebo. The poster's allocation and identity are unverified. Comments claiming calcitonin causes all fatigue or that eloralintide is essentially side-effect-free are interpretations, not trial findings. No population incidence, comparative safety or treatment advice follows. Next: formal tolerability results; no new date verified.

**Sources:** [Primary source 1](https://www.reddit.com/r/GLP1ResearchTalk/comments/1x0wctl/glp1dacra_combo_trial/); [Primary source 2](https://www.pfizerclinicaltrials.com/nct07575932-overweight-or-obesity-trial).

## Dated history

### 2026-10-02 — Scheduled focused review

2 newly recorded findings or milestones; primary evidence, uncertainty and incomplete coverage are detailed above and in the [run record](../updates/2026-10-02_scheduled_research_update.md). Full-topic successful-check dates remain unchanged.

- **2026-09-29:** 3 sourced entries, 2 cross-topic links and 0 informal-source checks. [Coverage and gaps](../updates/2026-09-29_scheduled_research_update.md).

- **2026-09-27:** 3 sourced entries and 1 cross-topic links from a focused scheduled check. [Coverage and remaining gaps](../updates/2026-09-27_scheduled_research_update.md).

- **2026-09-22:** Focused scheduled research retry; 3 sourced entries and 3 cross-topic links. [Coverage and gaps](../updates/2026-09-22_scheduled_research_update.md).

### Dated findings

- 2026-09-12: Initial brief established from FDA documents, publications, registries, and dated sponsor updates. Announced future windows are separated from completed results.
- 2026-09-13: Historical coverage correction for the Atlas compound histories. Tirzepatide’s documented phase 1 study began [May 11, 2016](https://trials.lilly.com/en-US/trial/319715), phase 2 began [May 24, 2017](https://trials.lilly.com/en-US/trial/137151), and phase 3 SURPASS-4 began [November 20, 2018](https://trials.lilly.com/en-US/trial/203715). The plotted [SURPASS-2 results](https://pubmed.ncbi.nlm.nih.gov/34170647/) were published June 25, 2021, before [Mounjaro’s May 13, 2022 U.S. approval](https://www.fda.gov/drugs/drug-trials-snapshots/drug-trials-snapshots-mounjaro). Selected preapproval evidence was also recovered for liraglutide and semaglutide. These are historical additions, not new efficacy findings or a full current-program review. See the [coverage correction record](../updates/2026-09-13_development_history_correction.md) for scope and remaining gaps.

### 2026-09-14 — Ad-hoc focused review

STEP Young phase 3 topline, September 7; newly added within overlap window. Original event dates and sources are recorded above; unchanged historical trial results remain dated. STEP Young numerical primary BMI effect and detailed adverse events not in topline; pediatric cohort differs from registry-wide planned enrollment. No new VK2735 maintenance result in current sponsor releases. Informal search surfaced reposted STEP Young data and speculative conference expectations, without a distinct verifiable new rumor.

### 2026-09-18 — Scheduled focused review

CRB-913 new mechanism and sponsor results; Lilly EASD schedule, STEP Young repeat; Viking maintenance and major pipeline discovery queries. Original event dates, safety and limitations are retained in the September 18 update above. The complete-topic successful-check date was not advanced because the listed gaps remain. [Run record](../updates/2026-09-18_scheduled_research_update.md).