{
 "page": "https://jabbitapp.com/research/hu6-dnp-prodrug-rivus-fat-burner-evidence-teardown.html",
 "checked": "2026-10-27",
 "note": "Quotes asserted against cached copies. No doses, sellers, prices or stacking. X posters are private individuals and are not named.",
 "pubmed": {
  "37806314": {
   "title": "Safety and efficacy of once-daily HU6 versus placebo in people with non-alcoholic fatty liver disease and high BMI: a randomised, double-blind, placebo-controlled, phase 2a trial",
   "quotes": [
    "HU6 is a controlled metabolic accelerator that is metabolised in the liver to the mitochondrial uncoupler 2,4-dinitrophenol",
    "80 adults (39 [49%] women and 41 [51%] men)",
    "for 61 days",
    "-26·8% (SD 17·4)",
    "-35·6% (13·8)",
    "-33·0% (18·4)",
    "and 5·4% (19·8) for the placebo group",
    "No serious TEAEs were reported.",
    "flushing (19 [32%] participants), diarrhoea (15 [25%] participants), and palpitations (seven [12%] participants) were the most frequently reported TEAEs",
    "in the placebo group, two [10%] participants had flushing, none had diarrhoea, and one [5%] had palpitations",
    "There were no deaths.",
    "Rivus Pharmaceuticals."
   ]
  },
  "40072462": {
   "title": "Novel Controlled Metabolic Accelerator for Obesity-Related HFpEF: The HuMAIN-HFpEF Randomized Clinical Trial",
   "quotes": [
    "Of 66 participants randomized",
    "56 completed the trial",
    "between-group difference, -2.86 kg; 95% CI, -4.68 to -1.04 kg; P = .003",
    "total fat mass (between-group difference, -2.96 kg; 95% CI, -4.50 to -1.42 kg; P < .001)",
    "with no significant loss of muscle mass",
    "There were no statistically significant changes in peak VO2, 6-minute walk distance, Kansas City Cardiomyopathy Questionnaire score",
    "Serious adverse events were noted in 5 participants (4 in the HU6 group; 1 in the placebo group), including 1 death, all judged unrelated to treatment.",
    "treatment with HU6 for 19 weeks led to modest but statistically significant weight loss without significant changes in peak VO2"
   ]
  },
  "38924328": {
   "title": "A novel controlled metabolic accelerator for the treatment of obesity-related heart failure with preserved ejection fraction: Rationale and design of the Phase 2a HuMAIN trial",
   "quotes": [
    "Current weight loss strategies (diet, drug, and surgical) work through decreased energy intake rather than increased expenditure",
    "Mitochondrial uncoupling agents may have unique beneficial effects by producing weight loss via increased catabolism rather than reduced caloric intake"
   ]
  },
  "21739343": {
   "title": "2,4-dinitrophenol (DNP): a weight loss agent with significant acute toxicity and risk of death",
   "quotes": [
    "DNP is sold mostly over the internet under a number of different names as a weight loss/slimming aid.",
    "the classic symptom complex associated with toxicity of phenol-based products such as DNP is a combination of hyperthermia, tachycardia, diaphoresis and tachypnoea, eventually leading to death.",
    "To date, there have been 62 published deaths in the medical literature attributed to DNP."
   ]
  },
  "17475379": {
   "title": "Dinitrophenol and obesity: an early twentieth-century regulatory dilemma",
   "quotes": [
    "In the early 1930s, the industrial chemical dinitrophenol found widespread favor as a weight-loss drug",
    "the compound's therapeutic index was razor thin and it was not until thousands of people suffered irreversible harm",
    "it took passage of the Food, Drug, and Cosmetic Act in 1938 before federal regulators had the ability to stop patent medicine men from selling dinitrophenol"
   ]
  },
  "24913328": {
   "title": "Diet pills and the cataract outbreak of 1935: reflections on the evolution of consumer protection legislation",
   "quotes": [
    "An outbreak of cataracts in 1935 caused by dinitrophenol (DNP), the active ingredient of popular diet pills",
    "medical opinion concerning the safety of DNP may have contributed to the voluntary withdrawal of the diet drug from the market"
   ]
  },
  "34812657": {
   "title": "International trends in systemic human exposures to 2,4 dinitrophenol reported to poisons centres",
   "quotes": [
    "Responses were received from poisons centres in 38 countries which reported 456 separate cases of DNP exposure",
    "Annual case numbers increased from 4 in 2010 to 71 in 2015, with subsequent reductions to 53 in 2019.",
    "case fatality was high (11.9%, 95% CI 9.0, 15.4)"
   ]
  },
  "33021407": {
   "title": "Toxicoepidemiology and predictors of death in 2,4-dinitrophenol (DNP) toxicity",
   "quotes": [
    "There were 204 cases (n = 86, US; n = 118, UK) of systemic DNP exposure identified, of which 86% were under the age of 40 and 71% were males.",
    "US 11.6%; 95% CI: 6.4-20.1%: UK 16.9%; 95% CI: 11.3-24.7%",
    "Tachycardia, hyperpyrexia, acidosis, and agitation/confusion are independent risk factors for mortality"
   ]
  },
  "24957806": {
   "title": "Increasing frequency of severe clinical toxicity after use of 2,4-dinitrophenol in the UK: a report from the National Poisons Information Service",
   "quotes": [
    "Of the 30 separate systemic exposures to DNP reported by telephone to NPIS during the study period",
    "There were five (17%, 95% CI 6.9% to 34%) fatalities, four involving acute overdose.",
    "Commonly reported clinical features were fever (47%), tachycardia (43%), sweating (37%)",
    "a median age of 23.5 years"
   ]
  },
  "41838137": {
   "title": "Molecular mechanisms of mitochondrial uncoupling: focus on 2,4-dinitrophenol",
   "quotes": [
    "used as an anti-obesity treatment until it was withdrawn due to high toxicity, a narrow therapeutic window, and a lack of an antidote.",
    "Despite these concerns, DNP’s efficacy surpasses that of many contemporary anti-obesity drugs, sparking renewed interest in its potential use under controlled conditions."
   ]
  },
  "33567185": {
   "title": "Once-Weekly Semaglutide in Adults with Overweight or Obesity",
   "quotes": [
    "The mean change in body weight from baseline to week 68 was -14.9% in the semaglutide group as compared with -2.4% with placebo"
   ]
  }
 },
 "disclosures": {
  "37806314": "is a minor shareholder or has stocks in Anaetos, Rivus Pharma",
  "38924328": "has been a consultant for AstraZeneca, Pfizer, Corvia Medical, Bayer, Boehringer-Ingleheim, NovoNorDisk, Rivus",
  "41838137": "The authors declare no conflict of interest."
 },
 "pubmed_search_hu6_mash": {
  "term": "HU6[tiab] AND (MASH OR steatohepatitis OR M-ACCEL)",
  "ids": [
   "37806314"
  ]
 },
 "press_releases": {
  "rivus_2025-06-24": [
   "Jun 24, 2025",
   "met its primary endpoint",
   "A total of 221 adult patients were randomized",
   "Treatment with HU6 was associated with entirely fat-specific weight loss, with no significant change in lean mass at any dose.",
   "no treatment-related serious adverse events",
   "Three quarters of the fat loss was from the visceral fat compartment",
   "CMAs increase metabolism in a manner that is consistent and imperceptible to the patient by leveraging the natural metabolic process of mitochondrial uncoupling."
  ],
  "rivus_2025-11-07": [
   "November 7, 2025",
   "Late-Breaker Oral Presentation at AASLD The Liver Meeting",
   "analysis of 228 patients",
   "-29.4%, -31.2%, -27.0%",
   "versus -6.7% with placebo",
   "57%, 58%, and 50% of patients achieving a response",
   "versus 22% for placebo",
   "(-2.4%, or -2.6 kg,",
   "Weight loss was entirely fat-selective, with lean and skeletal muscle mass preserved.",
   "gastrointestinal disorders (14% with HU6 versus 16% with placebo)",
   "Low discontinuation rate (<5%)",
   "Across three Phase 2 trials, all of which met their primary endpoints"
  ],
  "rivus_2026-04-14": [
   "April 14, 2026",
   "Top-line data expected in mid-2027",
   "will enroll up to 180 patients with F2/F3 MASH",
   "for six months",
   "With over 500 patients treated to date",
   "a clinical-stage biopharmaceutical company"
  ]
 },
 "fda_2026-06-04": [
  "[6-4-2026]",
  "2,4-dinitrophenol in the nighttime (“pm”) tablets not listed on the product label",
  "is illegally marketed as a weight-loss product and is not approved by the FDA for any use",
  "long-term exposure can damage the eyes, skin, bone marrow, nervous system and heart",
  "DNP toxicity also can cause dangerously high body temperature, rapid heart rate and breathing, cardiac arrest and death."
 ],
 "x": [
  "impression_count 1295390",
  "HU6 is basically like DNP but you can’t kill yourself with it",
  "impression_count 5200",
  "A tier = HU6, Ozempic, phentermine, tesamorelin",
  "\"DEATH TIER\" = DMAA, sibutramine, DNP",
  "Oct 20-27: 26 posts"
 ],
 "clinicaltrials_gov": {
  "query": "intervention HU6",
  "count": 11,
  "by_phase": {
   "PHASE1": 6,
   "PHASE2": 5
  },
  "trials": [
   {
    "nct": "NCT04463017",
    "title": "Ascending Dose Study of HU6 in Healthy Volunteers",
    "status": "COMPLETED",
    "phase": [
     "PHASE1"
    ],
    "enrollment": 64,
    "sponsor": "Rivus Pharmaceuticals, Inc.",
    "has_results": false
   },
   {
    "nct": "NCT05433506",
    "title": "Safety and Pharmacokinetics of HU6",
    "status": "COMPLETED",
    "phase": [
     "PHASE1"
    ],
    "enrollment": 30,
    "sponsor": "Rivus Pharmaceuticals, Inc.",
    "has_results": false
   },
   {
    "nct": "NCT04709913",
    "title": "Multiple Ascending Dose Study of HU6 in High BMI Volunteers",
    "status": "COMPLETED",
    "phase": [
     "PHASE1"
    ],
    "enrollment": 30,
    "sponsor": "Rivus Pharmaceuticals, Inc.",
    "has_results": false
   },
   {
    "nct": "NCT06486558",
    "title": "Relative Bioavailability Study of HU6",
    "status": "COMPLETED",
    "phase": [
     "PHASE1"
    ],
    "enrollment": 43,
    "sponsor": "Rivus Pharmaceuticals, Inc.",
    "has_results": false
   },
   {
    "nct": "NCT05284617",
    "title": "Exploratory Ph 2A, Double-Blind, Placebo-Controlled Dose Escalation Study of Safety, Tolerability, PD, & PK of HU6 for Subjects With Obese HFpEF",
    "status": "COMPLETED",
    "phase": [
     "PHASE2"
    ],
    "enrollment": 67,
    "sponsor": "Rivus Pharmaceuticals, Inc.",
    "has_results": false
   },
   {
    "nct": "NCT07491458",
    "title": "A Trial to Investigate Safety, Exposure, and Efficacy of HU6 Compared With Placebo in Adult Participants With Metabolic Dysfunction-associated Steatohepatitis (MASH)",
    "status": "RECRUITING",
    "phase": [
     "PHASE2"
    ],
    "enrollment": 180,
    "sponsor": "Rivus Pharmaceuticals, Inc.",
    "has_results": false
   },
   {
    "nct": "NCT07170189",
    "title": "Phase 1, Open-Label, Randomized, Study of the Safety and Pharmacokinetics of HU6",
    "status": "COMPLETED",
    "phase": [
     "PHASE1"
    ],
    "enrollment": 59,
    "sponsor": "Rivus Pharmaceuticals, Inc.",
    "has_results": false
   },
   {
    "nct": "NCT06325930",
    "title": "A Study to Investigate the Absorption, Metabolism, and Excretion of [14C]-HU6",
    "status": "COMPLETED",
    "phase": [
     "PHASE1"
    ],
    "enrollment": 8,
    "sponsor": "Rivus Pharmaceuticals, Inc.",
    "has_results": false
   },
   {
    "nct": "NCT06104358",
    "title": "Ph 2a Study of HU6 on Energy Metabolism, Muscle and Liver Substrate Metabolism, and Mitochondrial Function in Subjects Who Are Overweight or Obese With Type 2 Diabetes",
    "status": "WITHDRAWN",
    "phase": [
     "PHASE2"
    ],
    "enrollment": 0,
    "sponsor": "Rivus Pharmaceuticals, Inc.",
    "has_results": false
   },
   {
    "nct": "NCT05979779",
    "title": "Ph 2 Study of the Safety and Efficacy of Three HU6 Dose Levels and Placebo in Nonalcoholic Steatohepatitis",
    "status": "ACTIVE_NOT_RECRUITING",
    "phase": [
     "PHASE2"
    ],
    "enrollment": 219,
    "sponsor": "Rivus Pharmaceuticals, Inc.",
    "has_results": false
   },
   {
    "nct": "NCT04874233",
    "title": "Phase 2a Study of HU6 in Subjects With Elevated Liver Fat and High BMI Volunteers",
    "status": "COMPLETED",
    "phase": [
     "PHASE2"
    ],
    "enrollment": 80,
    "sponsor": "Rivus Pharmaceuticals, Inc.",
    "has_results": true
   }
  ]
 },
 "liver_fat_chart": {
  "phase2a_61_days_pct": {
   "placebo": 5.4,
   "dose_groups": [
    -26.8,
    -35.6,
    -33.0
   ]
  },
  "m_accel_26_weeks_pct": {
   "placebo": -6.7,
   "dose_groups": [
    -29.4,
    -31.2,
    -27.0
   ]
  }
 },
 "dnp_chart": {
  "poisons_centre_cases": {
   "2010": 4,
   "2015": 71,
   "2019": 53
  },
  "case_fatality_pct": {
   "38 countries, 2010 to Sept 2020": 11.9,
   "US 2007-2018": 11.6,
   "UK 2007-2018": 16.9
  }
 }
}