# Localized fat removal [Home](../README.md) · [Aesthetics & Dental](../WATCHLIST.md#aesthetics) · [Calendar](../MILESTONES.md) Tags: [Drugs and biologics](../BROWSE.md#drugs) · [Devices and procedures](../BROWSE.md#devices-procedures) · [During or after weight loss](../BROWSE.md#after-weight-loss) ## Current state SCULPT registers a ten-person within-patient topical thigh study using circumference as its primary endpoint. It does not establish local fat-volume reduction or cellulite smoothing; CBL-514, other injectable programs and visceral-fat evidence retain their own development and safety limits. Status: active. Baseline and expanded scope reviewed September 12, 2026; focused review, not a systematic review. Includes regional subcutaneous fat and visceral fat. ## Questions to follow - Follow notable formal human drug programs for regional fat reduction, including CBL-514, RZL-012 and emerging alternatives. Include abdominal, flank, chin and other studied body sites. - Follow visceral-fat reduction and tesamorelin's potential new indications, especially evidence beyond its approved HIV-related population. Distinguish a new formulation from a new indication. - Track treated body sites, study population, objective fat-volume measurements, comparator, durability, local tissue effects, pain, other harms, and regulatory status. - Follow Phase 3 SUPREME studies and any human combination trials with GLP-1 therapies, including tirzepatide. - Keep subcutaneous fat, visceral adipose tissue (VAT), liver fat, overall weight loss and prevention of weight regain as separate endpoints. Track cosmetic improvement, metabolic outcomes and durability separately. Do not extrapolate animal findings into human efficacy or reduced VAT into proven cardiovascular benefit. - Add newly identified human-stage entrants within this scope. Kybella/deoxycholic acid is an established comparator; watch meaningful new formal indications or trials. Exclude gray-market injection mixtures and routine clinic advertising. ## Programs and next milestones ### Focused update — 2026-10-16 No additional finding was selected from these checked sources. Coverage remains incomplete; this is not a full-topic “no news” conclusion. **Remaining gaps:** Read current canonical README, HOW_THIS_WORKS, WATCHLIST, catalog, state, LATEST, MILESTONES, LANDSCAPE and this entire topic page. Search window September 5–October 16 preserves overlap from September 12 full successful check; October 14–16 changes prioritized and all saved October 13 material deduplicated. Retrieved every page of bounded ClinicalTrials.gov discovery (100 returned records) and all 15 named records. Retrieved records were selectively appraised; incidental matches excluded. Do not advance full successful-check timestamp.; CBL-514 SUPREME-01 NCT07140939 remains recruiting, 320 planned, actual start September 1, 2026, July 2027 primary and September 2027 final completion estimates; record last posted September 22. No new Phase 3 efficacy, recruitment-completion announcement, or second newly registered pivotal study verified. Caliway news index still returns the saved October 2 MRI/EASD material and September 23 first-dosing announcement. Do not infer enrollment counts from recruitment status.; RZL-012 China Phase 3 report and year-end filing forecast, CBL-514 MRI findings, tesamorelin and cellulite records were deduplicated against current canonical history. Changes in subcutaneous, visceral and liver fat remain separate from weight loss and clinical outcomes. Broad discovery includes incidental lifestyle/other-condition records; retrieval does not establish a complete entrant census.; International registries, every aesthetic device/procedure, complete conference appendices, and full-text rare-harm review remain incomplete; no new result selected from the bounded searches is not a claim of no news. **Informal-source coverage:** Targeted Reddit queries for CBL-514/CBL514, cellulite and October 2026 plus named-source searches did not yield a selected new specific informal claim. Indexed search is incomplete, including unindexed comments and audio; no claim that rumors are absent. [Full coverage record](../updates/2026-10-16_scheduled_research_update.md). ### Focused update — 2026-10-13 No additional finding was selected from these checked sources. Coverage remains incomplete; this is not a full-topic “no news” conclusion. **Remaining gaps:** Read canonical README, HOW_THIS_WORKS, WATCHLIST, catalog, state, LATEST, MILESTONES, LANDSCAPE and assigned current topic. September 5–October 13 window preserves seven-day overlap from September 12 full successful check. Retrieved every page of bounded public registry discovery (90 returned records; incidental matches excluded), and all named records. Full successful-check date must remain unchanged.; Europe PMC retrieval now succeeded, closing prior HTTP503 access failure. Initial broad query downloaded up to 100 per topic with many incidental/nonhuman matches; title/abstract MED retry retrieved hair 97/97, skin 27/27, scars 25/25, dental 100/147. Retrieved records are not an exhaustive worldwide full-paper/safety appraisal.; SUPREME-01 remains recruiting 320 with July/September 2027 estimated completion and unchanged September 22 posting. SCULPT, CBL-0206, AYP-101, RZL-012 and tesamorelin named statuses/results remain as saved; no new China NDA acceptance, SUPREME-02 initiation or non-HIV tesamorelin indication verified. Caliway index still ends October 2; original EASD subgroup tables, broader cellulite comparative outcomes and rare-harm/regulator inventory remain gaps. Theratechnologies news page failed retrieval. **Informal-source coverage:** October 10 HeliosClinical and October 12 gerosciencee CBL514 posts repeat the already saved EASD source; no independent confirmation. Recent tesamorelin self-experiment/sourcing posts excluded from formal-program efficacy; no new attributable trial timing signal selected. Full investor and podcast audio remains unreviewed. [Full coverage record](../updates/2026-10-13_scheduled_research_update.md). ### Focused update — 2026-10-09 #### SCULPT registers a small placebo-controlled topical fat and cellulite study **Source date:** October 7, 2026 first registry posting. **Evidence:** registered human pilot; no results. SCULPT/NCT07862920, led by Frank Greenway at Pennington Biomedical, plans 10 women aged 18–50 with BMI 25–35 and self-reported thigh cellulite. Each participant will apply active naringenin/beta-carotene/menthol cream to one thigh and placebo to the other for eight weeks, with randomized side assignment and participant/provider/investigator masking. The primary endpoint is the between-thigh difference in girth. Photographic smoothness and microdialysis lipolysis are described in the narrative, but not fully specified as structured outcomes. This is a within-person design despite a structured “parallel” label. **Limitations and safety:** Ten participants and circumference do not establish selective adipose-volume loss, cellulite-dimpling improvement, durability, or general safety. No results are posted. The record does not establish a new U.S. therapeutic authorization or efficacy of retail formulations. **Next:** actual start; January 15, 2027 start and July 15, 2027 primary/final completion are registry estimates, not publication commitments. [Original registry](https://clinicaltrials.gov/study/NCT07862920). **Remaining gaps:** Read the current assigned topic and canonical scope/state. Named original registry records refreshed; all pages of broad ClinicalTrials.gov discovery for September 5–October 9 were retrieved (205 records, with incidental matches excluded). This honors the seven-day overlap from the saved September 12 full successful check.; Europe PMC original-literature discovery again returned HTTP 503. Targeted primary publisher, sponsor and conference searches were performed, but the worldwide paper/regulator/procedure and original-audio census remains incomplete. Preserve last_successful_check_utc.; SUPREME-01 remains recruiting 320, last posted September 22; CBL-0206 records, AYP-101 completed/no results, tesamorelin and RZL-012 records retain saved status. Caliway index still ends with October 2 EASD report. No new SUPREME-02, China NDA filing or broader tesamorelin indication verified.; A newly posted Assiut 40-person double-chin cohort NCT07864246 is not yet recruiting and has only one broadly described group; no randomized modality comparison or result. Not promoted as efficacy. Full original CBL-514 EASD tables, cellulite comparative census and regulator/rare-harm review remain gaps. **Informal-source coverage:** October 7 BodyHackGuide thread https://www.reddit.com/r/BodyHackGuide/comments/1wzmfif/down_30_on_rt_what_else_to_add/ and October 9 tesamorelin/blend discussion are self-experimentation, not formal-program outcomes or attributable development forecasts. Existing CBL-514 sourcing threads were deduplicated. No new rumor selected; full investor/podcast recordings incomplete. [Full coverage record](../updates/2026-10-09_scheduled_research_update.md). ### Focused update — 2026-10-06 No additional material finding was verified in the selected sources. Coverage remains incomplete; this is not a full-topic “no news” conclusion. **Coverage:** CBL-514 RZL-012 tesamorelin cellulite trial October 2026; cellulite randomized trial October 2026 treatment; site:caliwaybiopharma.com/en/news-detail 2026 October; site:theratech.com tesamorelin September October 2026; ClinicalTrials.gov named programs AND LastUpdatePostDate 2026-09-05 to 2026-10-06; broader regional-fat/cellulite discovery 2026-09-25 to 2026-10-06; EuropePMC TITLE_ABS discovery FIRST_PDATE:[2026-09-05 TO 2026-10-06] (HTTP503 coverage gap) **Remaining gaps:** Prior October2 CBL-514 EASD pooled VAT subgroup and September23 first-dose release deduplicated. SUPREME01 remains recruiting320 with July2027 primary/September2027 final estimates; AYP101 completed252, no posted results. Tesamorelin NCT03375788 remains completed51 with old posted results; no new indication asserted. Existing EGRIFTA formulation remains separate from HIV indication.; RZL012 named phase2 records unchanged; no new China NDA filing/readout verified. No new regional-fat or cellulite entrants returned in date-filtered search. Full original EASD tables, SUPREME02 current matched registry, updated global cellulite comparisons, regulator census and rare-harm inventory remain incomplete. Broad EuropePMC discovery failed503.; Focused source checks completed, but full-topic coverage incomplete; preserve original last_successful_check_utc. Recent registry discovery covered September25–October6; named-program checks and web discovery included the September5 overlap. This is not an exhaustive worldwide registry or literature review. **Informal-source coverage:** Targeted Reddit/talk searches found October2–5 CBL514 self-experiment/sourcing threads and tesamorelin/retatrutide anecdotes, excluded from formal-development efficacy. Permalinks searched: https://www.reddit.com/r/Biohacking/comments/1ww4w3j/cbl514/ and https://www.reddit.com/r/BodyHackGuide/comments/1sschiz/does_anyone_have_first_hand_experience_with_cbl514/ . No new attributable formal trial rumor selected; incomplete podcast/full transcript review. [Full coverage record](../updates/2026-10-06_scheduled_research_update.md). ### Focused update — 2026-10-02 #### CBL-514 human MRI subgroup suggests visceral-fat reduction **Source/event date:** 2026-10-02. **Evidence:** EASD conference report reproduced by sponsor; exploratory human subgroup. Caliway posted the EASD press-room report on October 2 after the September 30 presentation. A pooled MRI subgroup from CBL-0204/0205 included 41 people at baseline (23 CBL-514, 18 placebo) and 40 with late follow-up (23, 17). At four weeks after final treatment, visceral-fat volume changed −12.01% versus +5.68%; at the pooled 8–12-week follow-up, −10.45% versus +11.76%. The latter is a 22.21-percentage-point difference, not 22.21% absolute fat loss. These selected, small, short-term data do not establish sustained metabolic or cardiovascular benefit. Follow-up timing differs between the two pooled trials; confidence intervals and full missing-data methods were unavailable. The report describes mainly temporary injection-site reactions and no serious adverse events, without a detailed subgroup safety table. Claims about limiting weight regain after stopping tirzepatide remain animal evidence. CBL-514 is investigational. SUPREME-01 recruitment continues; end-2027 pivotal results are an expectation in this report, separate from registry-estimated July 2027 primary completion. **Next milestone:** SUPREME-01 primary completion July 2027 registry estimate; pivotal results end-2027 conference forecast. [Source 1](https://www.caliwaybiopharma.com/en/news-detail/-CBL-514-EASD-2026-subcutaneousfat-visceralfat-reduction-study-ENG/); [Source 2](https://clinicaltrials.gov/study/NCT07140939). **Coverage:** CBL514 EASD2026 human visceral fat analysis September30 October2; SUPREME01 AYP101 tesamorelin original registries; CBL514 tesamorelin RZL012 cellulite new human results informal signals. **Remaining gaps:** Conference report is an exploratory pooled MRI subgroup, not a full peer-reviewed VAT trial report; selection, missingness and intervals need original tables. No independently verified SUPREME02 recruitment milestone, new RZL012 readout or complete cellulite-comparison census. Tesamorelin and AYP101 API refreshed; no new result selected. **Informal-source coverage:** Sponsor LinkedIn confirms the EASD talk occurred; separate gray-market/self-experimentation claims excluded. No new attributable informal timing or efficacy claim selected. **Next update:** SUPREME-01 primary completion July 2027 registry estimate; pivotal readout end-2027 conference forecast. Other depots and programs retain separate dates. [Full coverage record](../updates/2026-10-02_scheduled_research_update.md). ### Focused update — 2026-09-29 #### SUPREME-01 first participant dosed; recruitment continues **Source date:** 2026-09-23. **Event date:** exact date not disclosed. **Date basis:** announcement. **Evidence:** sponsor development announcement; registry cross-check. Caliway reports that its pivotal abdominal-fat study has entered treatment, beyond the earlier recruitment announcement. SUPREME-01/CBL-0301, NCT07140939, plans 320 participants in the U.S. and Canada in a blinded randomized placebo comparison. The sponsor reports first dosing and continuing recruitment. The September 22 registry remains recruiting, with actual study start September 1 and estimated primary/final completion July/September 2027. **Limitations:** September 23 is the announcement date; the exact first-dose day is undisclosed. Treatment initiation supplies no Phase 3 efficacy result. Two-grade patient/clinician improvement is assessed separately from MRI fat-volume change. The same release’s new semaglutide/eloralintide combination findings are preclinical, not human weight-regain evidence. **Safety:** No new Phase 3 safety results. **U.S. status:** Investigational; recruitment does not establish routine U.S. availability. **Next milestone:** September 30 EASD presentation remains upcoming; July 2027 primary completion is a registry estimate, not a promised release. [Caliway first-dose announcement](https://www.caliwaybiopharma.com/en/news-detail/-CBL-514-SUPREME-01-FPI-ObesityWeek-2026-ENG/); [SUPREME-01 registry](https://clinicaltrials.gov/study/NCT07140939). **Coverage:** Selective September 5–29 overlap, emphasizing September 27–29; prior September 27 findings deduplicated. Refreshed SUPREME-01, AYP-101 and tesamorelin original API records; searched RZL-012, cellulite and new human-stage programs; recovered September 23 first-dose release. **Remaining gaps:** No new Phase 3 efficacy or independent SUPREME-02 enrollment milestone verified. September 30 VAT talk not yet occurred; full human abstract unresolved. Cellulite comparative census incomplete. **Informal-source coverage:** Reddit/talk and candidate searches mainly returned Dercum reposts and tesamorelin self-experimentation/sourcing, excluded; no new attributed formal-development rumor selected. **Next update:** September 30 CBL-514 presentation; primary completion July 2027 is a registry estimate, separate from sponsor-targeted 2027 topline. [Full coverage record](../updates/2026-09-29_scheduled_research_update.md). ### Focused update — 2026-09-27 #### Small lipedema trial finds no clear advantage for shockwave treatment **Source date:** 2026-09-24. **Event date:** 2026-09-24. **Evidence:** peer-reviewed randomized human study; primary abstract appraised. A small comparison found no significant between-group advantage of shockwave treatment over complex decongestive therapy for lipedema. Thirty-three patients, 11 per group, received six sessions of shockwave therapy, complex decongestive therapy, or both. Assessment two weeks after treatment covered DXA fat mass, leg volume, pain and quality of life. Fat-mass changes were small and did not significantly differ between groups. Leg volume, pain and quality-of-life improvements also did not significantly differ between groups. **Limitations:** Small sample, short follow-up and no untreated/sham group. Within-group improvement is not evidence of superiority or equivalence. The abstract provides no effect sizes or confidence intervals. Lipedema symptom/volume management must remain distinct from cosmetic fat removal, cellulite smoothing and durable fat-cell reduction. **Safety:** The authors describe the approaches as safe, but the available abstract provides no adverse-event counts. **U.S. status:** No new U.S. authorization or lipedema indication established. **Next milestone:** Full numerical results, safety tables, registration and longer controlled follow-up remain undated. [Original PubMed abstract](https://pubmed.ncbi.nlm.nih.gov/42785926/); [Original DOI](https://doi.org/10.1097/PHM.0000000000003164). **Coverage:** September 5–27 overlap with emphasis on September 23–27: CBL-514, RZL-012, AYP-101, tesamorelin, cellulite and human body-contouring/lipedema comparisons. Refreshed five original registry records and deduplicated CBL September 21/22 findings. **Remaining gaps:** SUPREME-01 remains recruiting, last posted September 22; September 30 visceral-fat presentation has not occurred. No independent new SUPREME-02 enrollment milestone established. AYP-101 remains completed without posted results. Tesamorelin record is unchanged; original liver-fat/VAT reporting limitations remain. Full cellulite-device comparative census and complete lipedema paper not appraised. **Informal-source coverage:** Targeted Reddit/talk searches for CBL-514, tesamorelin and cellulite mainly returned reposts of already recorded Dercum results, personal experiences and commercial claims; no new specific development rumor promoted. **Next update:** September 30 CBL-514 presentation; SUPREME-01 primary completion remains estimated July 2027, separate from sponsor-targeted 2027 topline. [Full coverage record](../updates/2026-09-27_scheduled_research_update.md). ### Focused update — 2026-09-22 #### CBL-514 reports reduced Dercum lipoma pain in Phase 2 **Source date:** 2026-09-21. **Event date:** 2026-09-21. **Evidence:** Sponsor topline announcement. Caliway's small placebo-controlled trial met its primary pain endpoint; the previously forecast September readout has occurred. CBL-0202DD/NCT06303570, randomized single-blind trial, registry n=19. Full-analysis-set pain change at week 20: −3.1 versus −1.9 points on a 0–10 scale, p=0.005. Week 24: −4.1 versus −1.7, p<0.0001. **Limitations:** Sponsor-only, small sample, no CIs or arm denominators recovered. Dercum's painful lipomas are distinct from cosmetic abdominal fat, visceral fat or cellulite. Separate full-analysis and per-protocol estimates. **Safety:** No drug-related serious AEs reported; mostly mild/moderate injection-site reactions, without arm-level counts. **U.S. status:** Investigational for this use; no new U.S. approval. **Next milestone:** Larger-trial timing unknown. Sponsor will assess lipedema-study feasibility; this is not a confirmed trial start. Separate visceral-fat presentation remains September 30. [Caliway September 21 Dercum readout](https://www.caliwaybiopharma.com/en/news-detail/CBL-514-CBL-0202DD-Phase2-met-primary-endpoint-ENG/); [NCT06303570 registry](https://clinicaltrials.gov/study/NCT06303570). #### SUPREME-01 registry now confirms recruitment and revises timing **Source date:** 2026-09-22. **Event date:** 2026-09-01. **Evidence:** Trial-registry update. The current record resolves the old not-yet-recruiting discrepancy for CBL-514's pivotal abdominal-fat trial. NCT07140939 posted September 22: RECRUITING; actual start September 1, 2026; planned enrollment 320. Primary completion July 2027 and overall completion September 2027, both estimates with month precision. Primary response requires ≥2-grade improvement on both patient and clinician abdominal-fat scales; MRI fat-volume change is secondary. **Limitations:** Registry status is not a result. Earlier sponsor initiation announcement was August 31; retain both dates with their source meanings. Prior 300/May 2027 record is superseded. **Safety:** No results posted. **U.S. status:** Investigational; trial recruitment does not establish availability outside a trial. **Next milestone:** Primary completion July 2027 (registry estimate); topline date not independently established. [NCT07140939 registry](https://clinicaltrials.gov/study/NCT07140939). **Coverage:** CBL-514 Dercum original readout, SUPREME-01 current status, RZL-012/AYP-101/tesamorelin and cellulite registry/source discovery. **Remaining gaps:** Full Dercum arm denominators, CIs and safety table absent; larger-trial timing unknown. No independently verified new RZL-012 result or tesamorelin new-indication result; aesthetic device comparative census incomplete. September 30 visceral-fat presentation has not occurred within this check. **Informal-source coverage:** Targeted CBL-514/tesamorelin/cellulite Reddit and talk searches mainly returned personal experience, gray-market sourcing and promotion; excluded. Sponsor lipedema feasibility statement remains a plan, not an active trial. [Full coverage record](../updates/2026-09-22_scheduled_research_update.md). **Next update:** **September 30:** CBL-514 presentation. SUPREME-01 registry primary completion now **July 2027**; pivotal topline remains a separate **2027 sponsor target**. ### Focused update — 2026-09-18 #### Focused-ultrasound body-contouring study registered **Source date:** 2026-09-03. **Evidence:** Historical evidence recovered. Linear Z adds a formal human device study for lower-abdomen and flank contouring. NCT07802431 was first posted on September 3 and is listed as recruiting. It plans to enroll 30 participants in a single-group, open-label study. Its primary endpoint is circumference change at day 90. **Limitations:** No sham comparator, no results, circumference is not equivalent to measured fat volume or cellulite improvement. September 1 start remains estimated, not confirmed first enrollment. **Safety:** Safety data pending. **U.S. status:** This registration does not establish a U.S. clearance or approval. **Next milestone:** Registry estimates primary completion December 20 and overall completion December 31, 2026; no release date. [NCT07802431 current primary registry](https://clinicaltrials.gov/study/NCT07802431). **Coverage:** Caliway news archive; fresh SUPREME, AYP-101 and tesamorelin registry records; new Linear Z device program; discovery searches for localized-fat and cellulite research. AYP-101 remains completed without posted results, and tesamorelin results are unchanged. This is a focused review, not a complete re-review of every program. **Remaining gaps:** Caliway latest release remains August 31; Dercum topline unverified while September window remains open. SUPREME registry remains March 30 not-yet-recruiting despite later sponsor enrollment report. No comprehensive cellulite comparative-paper review; EASD human VAT abstract remains unreviewed. **Informal-source coverage:** Reddit fat/tesamorelin/cellulite searches mainly returned gray-market sourcing, promotion or personal experience, excluded. September 15 durability discussion supplied mechanistic speculation without new formal research. [Full coverage record](../updates/2026-09-18_scheduled_research_update.md). ### Focused update — 2026-09-14 **Coverage:** No new CBL-514/RZL-012/AYP-101/tesamorelin human result verified in checked sources. SUPREME-01 registry remains March30 not-yet-recruiting while August31 sponsor says enrolling; no automatic completion inference. September30 EASD talk not yet occurred; human vs preclinical VAT content needs the abstract. Dercum results still unverified. Gray-market and generic promotional search results excluded; no new attributable in-scope rumor. This was a focused refresh, not a complete re-review of every program. Checked sources: [Source 1](https://www.caliwaybiopharma.com/en/news-detail/Caliway_Investor_Conference_Key_Takeaways_20260831_ENG/); [Source 2](https://clinicaltrials.gov/study/NCT07140939); [Source 3](https://clinicaltrials.gov/study/NCT06256445); [Source 4](https://clinicaltrials.gov/study/NCT03375788). **Next update:** CBL-514 presentation **September 30, 2026**, pivotal data sponsor-targeted for **2027**; RZL-012 China filing targeted **by end-2026**. AYP-101 and tesamorelin: **no firm next date**. Cellulite: no firm next result date. ### Current evidence and programs The named programs below target different fat depots and populations. Local injections studied for subcutaneous contouring and systemic therapies studied for VAT require separate assessments. General obesity-drug developments remain in [GLP-1 and related therapies](03_glp1.md), with cross-links for relevant depot-specific or combination findings. | Program | Main focus | Next meaningful update | | --- | --- | --- | | CBL-514 | Abdominal subcutaneous fat, combinations and exploratory VAT findings | September 30 human MRI subgroup is now reported; [findings and limitations](#cbl-514-human-mri-subgroup-suggests-visceral-fat-reduction). SUPREME-01 primary completion **July 2027** is a registry estimate; pivotal results **end-2027** are a separate conference forecast. Retreatment estimates extend into **2028**. | | RZL-012 | Chin fat and planned body-contouring development | China filing targeted **by end-2026**; full Phase 3 safety/results and body-trial start undated. | | AYP-101 | Chin fat | Phase 3 completed; results pending with **no dependable release date**. | | Tesamorelin | VAT and potential new populations/indications; separate liver-fat evidence | Non-HIV Phase 2 results already posted; watch publication and follow-on development. **No reliable new-indication date**. | Dates and their primary sources are detailed below. Kybella and MT921/NUVIJU provide approved-treatment context; CBL-514D/lipoma and cellulite programs are secondary indication watches. ### Baseline evidence #### September 12, 2026 — initial CBL-514 program anchors - **Source event date:** August 31, 2026. - **Evidence type:** sponsor development update. - **What changed:** Caliway reports that pivotal Phase 3 SUPREME-01 (CBL-0301) began enrollment in the U.S. and Canada. It also reports FDA IND clearance for a Phase 2 combination study of CBL-514 and tirzepatide. - **Interpretation:** These are development milestones. IND clearance permits a trial to proceed; it is not marketing approval. The source's weight-regain claims for the combination include animal evidence and do not establish human benefit. - **Next check:** verify registry status and trial design, additional SUPREME studies, planned readouts, and the combination trial's registration and enrollment. Reconcile estimated registry dates with newer dated sponsor reports. - **Primary source:** [Caliway, August 31, 2026](https://www.caliwaybiopharma.com/en/news-detail/Caliway_Investor_Conference_Key_Takeaways_20260831_ENG/). - **Registry anchor:** [SUPREME-01 / NCT07140939](https://clinicaltrials.gov/study/NCT07140939). - **Publication anchor for baseline review:** [Phase 2b paper / PMID 42159040](https://pubmed.ncbi.nlm.nih.gov/42159040/). Review the actual analysis population and missing-data handling before quoting efficacy percentages. These program anchors are supplemented by the evidence review below. #### September 12, 2026 — initial evidence baseline **Current assessment.** CBL-514 has placebo-controlled human evidence for reducing local abdominal subcutaneous fat, but remains investigational. The useful next question is whether larger blinded studies reproduce the effect with acceptable tolerability and durability. **Published Phase 2b — CBL-0204 / NCT05736107.** The May 20, 2026 paper randomized 108 adults, BMI between 18.5 and 30, to CBL-514 or placebo. MRI fat-volume change was −20.3% versus +0.1% four weeks after final treatment, and −17.3% versus +0.7% at 12 weeks. These percentages describe the assessed abdominal depot, not total body fat or weight. Clinician-rated improvement favored treatment, but investigators were unblinded, 38.9% discontinued early, and available analysis samples were smaller than the randomized sample. Injection-site reactions were common; pain occurred in 73.1% versus 36.4%, and some participants stopped for local reactions. The paper excluded visible abdominal panniculus, so it does not establish treatment of loose skin. These results warrant further trials, not a guaranteed personal outcome. [Full primary paper](https://academic.oup.com/asj/advance-article/doi/10.1093/asj/sjag092/8687971). **Pivotal development — SUPREME-01 / CBL-0301 / NCT07140939.** The registry snapshot last updated March 30, 2026 describes approximately 300 participants in a randomized placebo-controlled Phase 3 trial, with estimated primary completion in May 2027. It still says not yet recruiting; this conflicts with later sponsor announcements. Caliway's August 31 report says enrollment has begun and explains an updated primary endpoint based on two-grade improvement on both patient and clinician abdominal-fat rating scales, with MRI volume as a key secondary endpoint. Treat the registry date as an older estimate and the enrollment/endpoint changes as newer sponsor-reported information. [Registry](https://clinicaltrials.gov/study/NCT07140939); [August 31 sponsor update](https://www.caliwaybiopharma.com/en/news-detail/Caliway_Investor_Conference_Key_Takeaways_20260831_ENG/). **GLP-1 combination — CBL-0201WR.** The August 25 sponsor release reports IND clearance for a randomized Phase 2 CBL-514 plus tirzepatide study targeting 120 U.S. participants. This permits human testing; it is not marketing approval or a human efficacy result. Weight-regain claims remain to be tested. [Sponsor trial announcement](https://www.caliwaybiopharma.com/en/news-detail/CBL-514-CBL-0201WR-IND-APPROVAL-CBL-0301-IRB-APPROVAL-ENG/). **Expected next update.** Caliway announces an EASD presentation on **September 30, 2026**, on visceral-fat findings. The human analysis and preclinical contributions need appraisal when the abstract is available. For pivotal results, **2027 is a sponsor target**: Caliway’s May 22, 2026 release anticipates SUPREME toplines during 2027. The older May 2027 primary-completion estimate is not a promised release date. [Pivotal-program guidance](https://www.caliwaybiopharma.com/en/news-detail/U-S-FDA-IND-Clearance-CBL-0302-Global-Pivotal-Phase-3-CBL-514/). No reliable combination-trial readout date was verified. [September 30 announcement](https://www.caliwaybiopharma.com/en/news-detail/CBL-514-CBL-0201WR-IND-APPROVAL-CBL-0301-IRB-APPROVAL-ENG/). **Coverage limits.** The registry's indexed primary record was readable, but the live detail/API rendering was unreliable. Enrollment and protocol changes therefore retain explicit sponsor attribution. Reconcile them with a newer registry version at the next check. A focused September 13, 2026 live API check recovered the same March 30 record; the newer sponsor enrollment and protocol announcements remain unreconciled with the registry. #### September 12, 2026 — expanded CBL-514 tracking **Retreatment and durability — CBL-0206.** The June 4 registry snapshot for [Stage 1 / NCT07608770](https://clinicaltrials.gov/study/NCT07608770) lists a recruiting, randomized placebo-controlled Phase 2b study targeting approximately 250 adults, with MRI fat-volume endpoints and estimated primary completion in **April 2027**. The May 29 record for [Stage 2 / NCT07608757](https://clinicaltrials.gov/study/NCT07608757) describes an open-label, single-group retreatment extension, despite retaining the broader randomized-study wording in its title. It estimates a **February 2027** start and **February 2028** primary completion. These are registry estimates, not release dates. Both records exclude severe visceral fat; neither should be treated as established treatment evidence for that population. **Related local-fat indications.** Track major human results for CBL-514D in Dercum's disease lipomas and CBL-514 for cellulite as secondary programs, with their disease-specific endpoints. [CBL-0202DD / NCT06303570](https://clinicaltrials.gov/study/NCT06303570) lists 19 participants and actual primary completion on March 23, 2026. Caliway's [August 31 update](https://www.caliwaybiopharma.com/en/news-detail/Caliway_Investor_Conference_Key_Takeaways_20260831_ENG/) targets **September 2026** topline results. [Cellulite Phase 2 topline](https://www.caliwaybiopharma.com/en/news-detail/cbl-0201efp-topline-results/) was announced in April 2024; a dependable next readout date was not verified. Painful-lipoma or cellulite improvement is not interchangeable with general abdominal-fat reduction. **Visceral-fat presentation.** The September 30 EASD presentation is sponsor-announced. The August 25 release describes MRI-measured VAT findings, while August 31 also emphasizes preclinical work. The actual abstract, human sample and analysis were not verified in this expansion check; inspect them before interpreting the presentation as a new human VAT efficacy result. **Established comparator.** Kybella (deoxycholic acid) is FDA-approved for submental fullness in adults. Its label does not establish safe and effective use elsewhere. Keep it as context and watch major formal new-indication developments. [Current DailyMed label](https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=fe431ed4-ea6f-4e99-b4bc-ec25ae7b8553). #### September 12, 2026 — RZL-012 baseline **Program.** RZL-012, also indexed as utenpanium chloride and tapencarium, is an investigational local fat-reduction injection from Raziel. Follow chin fat and body-contouring development separately. [NLM compound aliases](https://pubchem.ncbi.nlm.nih.gov/compound/71526745); [U.S. Phase 2b chin study / NCT04867434](https://clinicaltrials.gov/study/NCT04867434); [small flank study / NCT05445557](https://clinicaltrials.gov/study/NCT05445557). **Latest evidence — sponsor topline, September 2, 2026.** Raziel and Fosun report a placebo-controlled China Phase 3 trial in 480 participants (360 active, 120 placebo). At day 84, the primary responder rate favored treatment by **30 percentage points**; this does not mean 30% fat-volume reduction. The release reports that endpoints were met but provides limited detailed safety and durability data. Full results are needed to appraise the effect and harms. [Sponsor announcement](https://www.prnewswire.com/news-releases/raziel-therapeutics-and-fosun-pharma-announce-positive-phase-3-results-for-rzl-012-in-submental-fat-reduction-clearing-the-path-to-a-china-nda-filing-302867570.html). **Next milestone and U.S. status.** The sponsors target a China NDA submission **by end-2026** and plan a body-contouring trial, without a verified start date. These are plans, not approvals. No U.S. approval or dependable U.S. pivotal-readout date was verified. Track the full Phase 3 publication, China filing/acceptance, and the new body-site protocol. **Earlier safety context.** Posted U.S. Phase 2b results include **151 actual participants**, rather than the originally planned 135. Dysphagia was reported in 15/50 high-dose recipients, 21/53 low-dose recipients and 2/48 placebo recipients; facial paralysis in 3/50, 1/53 and 0/48, respectively. No serious adverse events or deaths were reported. These events require attention when interpreting broad sponsor safety claims. The [registry results](https://clinicaltrials.gov/study/NCT04867434) and [published Phase 2b paper](https://pubmed.ncbi.nlm.nih.gov/37348516/) provide the starting evidence; the [12-person flank study](https://pmc.ncbi.nlm.nih.gov/articles/PMC10631968/) is much earlier body-area evidence. #### September 12, 2026 — AYP-101 emerging-program baseline **Program and evidence.** AMIpharm's AYP-101 is a phosphatidylcholine formulation studied for chin fat. A published Phase 2 randomized trial enrolled 96 Asian adults; at four weeks, evaluator-rated improvement occurred in 69.70% of the lower-dose group versus 22.58% with placebo. This is the evaluator scale, not a verified combined evaluator-and-patient response. Small size, short follow-up and a chin-specific population limit generalization. Claims of superior tolerability to deoxycholic acid based on separate trials are not head-to-head evidence. [Peer-reviewed report / PMID 40850886](https://pubmed.ncbi.nlm.nih.gov/40850886/). **Current stage and timing.** [Phase 3 / NCT06256445](https://clinicaltrials.gov/study/NCT06256445) enrolled 252 participants and completed October 30, 2025. The registry's January 22, 2026 update has no posted results. Watch **Phase 3 results and regulatory progress; no dependable release date or U.S. milestone was verified**. This formal investigational formulation should not be conflated with gray-market phosphatidylcholine injection mixtures. [Registry API record](https://clinicaltrials.gov/api/v2/studies/NCT06256445). **Overseas comparator.** Medytox lists cholic-acid injection MT921/NUVIJU as approved by Korea's MFDS. Keep overseas label changes or new body-site trials as secondary watch items; no U.S. milestone was verified. [Medytox development page](https://www.medytox.com/page/rndvision_en?site_id=en). #### September 12, 2026 — tesamorelin and visceral-fat baseline **Approved use.** Tesamorelin stimulates the growth-hormone axis; it is not a local fat-dissolving injection. EGRIFTA is FDA-approved for excess abdominal fat in adults with HIV-associated lipodystrophy. EGRIFTA WR's 2025 approval changed preparation convenience, not the indication. The label describes weight neutrality and unestablished long-term cardiovascular safety, with monitoring concerns including elevated IGF-1 and glucose intolerance. General-obesity, non-HIV VAT and MASLD/MASH use are not approved indications. [FDA EGRIFTA WR label](https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/022505s020lbl.pdf). **Human evidence beyond HIV.** A 12-month randomized placebo-controlled trial in 60 adults with abdominal obesity and reduced growth-hormone secretion found a VAT treatment effect of **−35 cm²** (95% CI −58 to −12), without significant subcutaneous-fat reduction. This selected population and surrogate endpoint do not establish general effectiveness or cardiovascular-event prevention. [NCT00675506 / published 2012 trial](https://pmc.ncbi.nlm.nih.gov/articles/PMC3513535/). **Liver-fat research.** In a separate 61-person randomized trial of HIV-associated fatty liver, tesamorelin reduced liver fat by 4.1 percentage points versus placebo at 12 months; existing fibrosis did not significantly improve. This is liver-fat evidence, not proof of MASH resolution or improved clinical liver outcomes. [NCT02196831 / published 2019 trial](https://pmc.ncbi.nlm.nih.gov/articles/PMC6981288/). **Non-HIV fatty liver — NCT03375788.** Massachusetts General Hospital's completed Phase 2 trial randomized 51 participants (26 tesamorelin, 25 placebo); 38 finished the 12-month randomized phase. Posted results, dated November 20, 2025, include only 18/16 participants in the primary liver-fat analysis. Median changes were **−5.3 versus +3.6**, labeled “percent change in hepatic fat fraction”; the registry does not resolve relative percent versus percentage points or supply a statistical comparison. Median activity-score and fibrosis-score changes were zero in both groups. **No numerical VAT outcome is posted.** Serious adverse events affected 2/26 versus 3/25; other adverse events 22/26 versus 15/25, with more arthralgia, edema and injection-site stinging in the tesamorelin group. These are small, incomplete-analysis registry results, not proof of general VAT or clinical liver-outcome benefit. [Registry and results](https://clinicaltrials.gov/study/NCT03375788); [verified API](https://clinicaltrials.gov/api/v2/studies/NCT03375788); [protocol](https://cdn.clinicaltrials.gov/large-docs/88/NCT03375788/Prot_SAP_000.pdf). **New-indication development and next update.** The sponsor's historical general-population NASH Phase 2b/3 proposal was awaiting a partner, with FDA protocol questions left unresolved in its filing. No current trial launch, broader indication decision or reliable future readout date was verified. Watch full publication and clarification of the posted non-HIV results, a funded follow-on trial, registration and first enrollment. Keep that proposed commercial program separate from the completed academic trial. [Sponsor filing](https://www.theratech.com/static-files/06747019-3734-4ddb-b635-a4f17c50f00a). **Registry quality check.** NCT07481734 explicitly identifies itself as a “Mock Study”; do not count it as a real tesamorelin development milestone. [Record](https://clinicaltrials.gov/study/NCT07481734). ### September 12, 2026 — cellulite scope and initial brief **Scope expansion.** Include formal human trials of cellulite drugs, septal-release procedures and devices, and collagen-stimulating injectables. Track appearance, durability, bruising, pigment change and downtime. Cellulite smoothing is a distinct endpoint from reducing fat volume, visceral fat or body weight; the CBL-514 cellulite program already noted above remains included. This section is a bounded subtopic check, not a repeat review of all fat-removal drugs. **Avéli.** FDA clearance [K221336](https://www.accessdata.fda.gov/cdrh_docs/pdf22/K221336.pdf) covers improved cellulite appearance in adult women's buttocks/thighs, supported through one year. Its septal-release study enrolled 74 participants without a randomized sham comparator. Blinded photo assessment met the prespecified improvement endpoint. Bruising was common (86.8%; median 27 days), and some adverse effects persisted at study exit. Clearance and one-year follow-up do not establish permanent correction, fat removal or comparative superiority. **Injectable context and emerging evidence.** Endo ceased Qwo production and sales in December 2022 over bruising variability and potential prolonged discoloration; commercial discontinuation should not be mislabeled as an FDA withdrawal of approval. [Sponsor filing](https://www.sec.gov/Archives/edgar/data/1593034/000159303424000007/endp-20231231.htm). A July 1, 2026 PLLA/Sculptra study reported investigator-rated improvement in 28/29 women at month nine. The small study lacks a stated randomized comparator in the abstract and cannot establish superiority or rare-harm rates. Nor does publication establish a U.S. cellulite indication. [Human study](https://pubmed.ncbi.nlm.nih.gov/42406356/). **Next update.** No dependable future cellulite readout date was verified. Watch new comparative studies, longer durability, actual label changes and any follow-on CBL-514 trial. Assess combined fat reduction/tightening/septal release by component so a cosmetic result is not attributed to the wrong mechanism. This initial search used FDA, sponsor and primary-study sources; informal cellulite leads were not exhaustively reviewed. ## Dated history ### 2026-10-02 — Scheduled focused review 1 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:** 1 sourced entries, 0 cross-topic links and 0 informal-source checks. [Coverage and gaps](../updates/2026-09-29_scheduled_research_update.md). - **2026-09-27:** 1 sourced entries and 0 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; 2 sourced entries and 0 cross-topic links. [Coverage and gaps](../updates/2026-09-22_scheduled_research_update.md). ### Dated findings The dated baseline entries are preserved under [Baseline evidence](#baseline-evidence). ### 2026-09-14 — Ad-hoc focused review No new CBL-514/RZL-012/AYP-101/tesamorelin human result verified in checked sources. Original event dates and sources are recorded above; unchanged historical trial results remain dated. SUPREME-01 registry remains March30 not-yet-recruiting while August31 sponsor says enrolling; no automatic completion inference. September30 EASD talk not yet occurred; human vs preclinical VAT content needs the abstract. Dercum results still unverified. Gray-market and generic promotional search results excluded; no new attributable in-scope rumor. ### 2026-09-18 — Scheduled focused review Caliway news archive; fresh SUPREME, AYP-101 and tesamorelin registry records; new Linear Z device program; discovery searches for localized-fat and cellulite research. AYP-101 remains completed without posted results, and tesamorelin results are unchanged. 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).