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Updated 2026-04-14 Atlas Adipotide deep dive Functional Evidence-ranked
Companion list · sections & rankings

Methods list, organised two ways

The same eighteen compounds and methods, sorted twice. The top half groups them by function — kill fat cells, push fat cells to empty faster, or sit in the "not worth pursuing" footnotes. The bottom half flattens everything into a single evidence rank for quick reference. The goal is a page you can scan before deciding whether to read the longer atlas entries.

By function

The core distinction is mechanism. Adipocyte-death methods physically destroy or remove fat cells. Lipolysis-stimulation methods empty existing fat cells faster, usually as a modifier on top of an active calorie deficit. The footnotes collect the methods that are either hype, abandoned, or preclinical-only and therefore should not carry weight in a practical writeup.

1. Adipocyte death

physical removal or induced cell death

These methods actually reduce the count of fat cells or the capillary-perfused adipose mass. Effect is permanent in the treated area but total body fat still follows energy balance — regrowth preferentially redistributes to untreated depots when diet is unchanged.

Strong human evidence
  • LiposuctionSurgical removal
    The baseline for local adipocyte reduction. RCT, DXA, MRI, and histology all confirm the treated depot stays reduced; the limitation is invasiveness and compensatory redistribution to visceral and upper-body depots under sedentary regain.
  • CryolipolysisCold-induced apoptosis
    ~3.56 cm abdominal circumference and ~5.22 mm suprailiac fat-thickness reduction at 12 weeks in the 2025 meta-analysis. PAH per-patient rate is ~0.22% — about 40× higher than the "1 in 20,000" figure still used in marketing.
  • Deoxycholic acid, submental (Kybella)Adipocytolysis
    Phase-3 RCT-supported for submental fat. Common local adverse events include ~4% marginal mandibular nerve paresis (all resolved) and ~2% dysphagia. Works, but indication is narrow.
Real mechanism, smaller or weaker effect
  • Thermal HIFU / focused ultrasoundLiposonix, UltraShape
    Histologic adipocyte destruction but sham-subtracted waist effect is ~1 cm. Inferior to cryolipolysis head-to-head. Liposonix has largely been displaced commercially.
  • Laser-assisted liposuctionSmartLipo, SlimLipo
    A liposuction variant with possibly better skin tightening. Signature complication is internal thermal burn — ~1–6% depending on device.
  • 1060 nm hyperthermic laserSculpSure
    ~8.5% or ~1.3 mm fat-thickness reduction at 12 weeks in the industry pivotal trial, no waist change, blinded-observer performance barely above chance.
  • Radiofrequency electric-fieldVanquish, TruSculpt
    Thermal apoptosis mechanism is real. Effects often hover near measurement error and the literature is industry-dominated.
  • Deoxycholic acid, off-label bodyAbdomen, flanks, arms
    Mechanism plausible. Evidence is case-series and small cohorts only. ASPS 2019 position statement explicitly does not recommend for routine non-submental use.
Emerging / watch list
  • CBL-514Caliway Biopharmaceuticals
    Injectable lipolytic. Phase-2b positive for abdominal fat (76.7% vs 18.9% responder at 12 weeks, >30% fat-thickness reduction, n≈107). Phase 3 ongoing; not approved.

2. Lipolysis stimulation

empty fat cells faster, possibly selectively

These methods do not remove fat cells. They modulate how quickly existing adipocytes release stored fat, usually by raising cAMP locally or by releasing adrenergic brakes on specific depots. Almost all require a concurrent calorie deficit to produce visible results — raising cAMP in an adipocyte with no lipolytic signal does not move fat off the body.

Weak helpers during active deficit
  • Topical aminophyllinePDE inhibition
    The deficit-dependent story holds: positive trials cluster in calorie-restricted arms, the one double-blind placebo trial (Collis 1999) was null in weight-stable participants. Depot selectivity is plausible (α2-rich gluteofemoral fat has its cAMP brake bypassed) but the cleanest evidence is weak.
  • Topical caffeineSame PDE pathway
    Literature is mostly cellulite and circumference. Independent placebo-controlled trials (Bielfeldt 2016) were null; the Lupi 2007 microcirculation endpoints were null. Not a selective-fat tool on any imaging endpoint.
Mechanism-interesting, human-evidence-weak
  • Yohimbine and α2 antagonistsReleases α2 brake
    The depot-selectivity mechanism that pairs conceptually with aminophylline. Controlled human trials (Kucio 1991 and descendants) have not demonstrated reliable preferential stubborn-fat loss. Real safety concerns include anxiety, hypertension, and monoamine-drug interactions.
Systemic, not local
  • Retatrutide and other incretinsGIP/GLP-1/glucagon
    Phase-2 body-composition substudy: ~24.5-39.1% VAT vs 13.2-43.5% ASAT at 48 weeks. This is the cleanest actual differential-fat signal in current medicine, but it is a medication, not a local lever — belongs in the GLP-1 track.

3. Footnotes

dead, disproven, regulator-warned, or preclinical-only

Collected here so that a reader encountering these terms in the wild can place them quickly. Each of these is either abandoned, shown not to work on proper endpoints, or exists only in animal / mechanistic literature without a human safety envelope.

Regulator-warned / gray market
  • PPC / Lipostabil / Aqualyx / LipodissolveUnapproved injection lipolysis
    FDA issued an early-2024 consumer safety communication against Aqualyx, Lipodissolve, Lipo Lab, and Kabelline. Brazil banned PPC in 2002. Mycobacterial abscesses, chronic nodules, and skin necrosis are documented complications.
Abandoned clinical candidates still sold as "research peptides"
  • Adipotidesee deep-dive page
    Phase 1 terminated at 4 patients over 6.5 years with no posted results. One publicly named dialysis case (Bostin Loyd, died 2022). Mechanism remains interesting; the drug is abandoned. Worth mention only as a footnote.
  • AOD9604Failed Phase 2B
    Metabolic Pharmaceuticals' hGH-fragment. OPTIONS trial (n=536) was negative. Now sold as a research peptide with no approved indication and no selective-fat evidence.
Hype / disproven
  • Low-level laser therapyZerona, Erchonia
    Positive trials are industry-dominated; the one independent mechanism study directly contradicted local fat loss claims.
  • Spot reduction via targeted exerciseCrunches, thigh adduction
    Ramirez-Campillo 2022 meta-analysis pooled effect -0.03 (CI crosses zero). Two small matched-EE local-plus-cardio trials suggest a marginal hedge, not a lever.
  • Glycyrrhetinic acidLicorice-derived topical
    One small unreplicated 2005 Armanini trial (n=9+9, ~0.3 cm waist differential). Nobody has tried to replicate it.
  • HIFEM alone (Emsculpt)Muscle-stim device
    Primarily a muscle-hypertrophy device. Any fat signal in Emsculpt NEO probably comes from the RF thermal component, not HIFEM. Evidence base >85% industry-author-affiliated.
  • Chromium / CLA / garcinia / generic "fat burners"OTC supplement category
    NIH ODS and NCCIH both describe these as having small, inconsistent, or clinically unimpressive effects. Not selective-fat tools by any endpoint.
Preclinical-only or out-of-scope
  • 5-amino-1MQNNMT inhibitor
    Mouse-only. No human trials. Interesting target, not a current option.
  • Topical capsaicinTRPV1 signalling
    Visceral-fat signal in DIO mice. No human depot-level evidence. Not in the category today.
  • Synephrine, forskolinOral stimulants
    Oral, weak, not depot-specific. No selective-fat-redistribution claim survives scrutiny.
  • ALCAR / oral carnitineCarnitine shuttle
    Small nonspecific general weight-management signal in some meta-analyses. Not a local-fat tool.

By evidence rank

The same list, flattened and ranked by adversarial scrutiny of the human evidence rather than by mechanism category. Useful for quick lookup of where anything sits on the "real / weak / hype" axis.

# Method Tier One-line framing
01LiposuctionEstablishedDefinite local adipocyte removal, limited metabolic benefit, credible compensatory redistribution signal. Modern mortality ~1 per 11,000 in accredited facilities.
02CryolipolysisEstablishedModest local reduction; PAH ~0.22% per patient in the 2025 meta-analysis — roughly 40× the old marketing figure.
03Deoxycholic acid, submentalEstablishedPhase-3 supported for submental fat only. Nerve paresis and dysphagia are real local risks.
04Thermal HIFU / focused ultrasoundNiche but plausibleHistologic adipocyte destruction, sham-subtracted ~1 cm waist. Inferior to cryolipolysis head-to-head.
05Laser-assisted liposuctionNicheLiposuction variant with 1–6% internal thermal burn risk. Not a separate miracle.
061060 nm SculpSure laserNiche but plausible~8.5% fat-thickness reduction at 12 weeks; no waist change; blinded-observer performance weak.
07Deoxycholic acid, body off-labelEvidence-weakMechanism-plausible, case-series evidence only. Explicitly non-recommended by ASPS for routine non-submental use.
08Radiofrequency electric-fieldNicheModest contour effects, industry-dominated literature, effects near noise.
09CBL-514Watch listPositive Phase 2b, Phase 3 ongoing. Not yet approved.
10Topical aminophyllineWeakWeak-helper tier. Cleanest independent blinded trial was null; positive literature is patent-holder-dominated.
11Topical caffeineWeakMostly cellulite / cosmetic literature. Imaging endpoints null in independent trials.
12Glycyrrhetinic acidWeakOne small unreplicated trial. Not worth pursuing.
13Spot reduction via exerciseDisprovenMeta-analytic effect ~0; two small matched-EE trials hedge but do not rescue.
14HIFEM alone (Emsculpt)MiscategorisedPrimarily a muscle-hypertrophy device being marketed as a fat-removal device.
15Low-level laser therapy (Zerona)HypeIndustry-dominated positive trials, independent mechanism study contradicts claims.
16AdipotideAbandonedPhase 1 terminated at n=4, one named dialysis case. Deep dive.
17AOD9604AbandonedFailed Phase 2B. Still sold as a research peptide.
18Classical PPC / Lipostabil / AqualyxRegulator-warnedFDA 2024 consumer safety communication, Brazilian ban, mycobacterial infection risk.
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