Retatrutide
Retatrutide is a Lilly triple GLP-1/GIP/glucagon agonist that produced 24.2% placebo-adjusted weight loss at 48 weeks in Jastreboff 2023 NEJM Phase 2 (n=338). It remains investigational with no FDA approval, no cardiovascular outcome data, and a real-world supply that is entirely unregulated gray-market peptide.
Retatrutide scored 5.5 / 10 (⚖️ Neutral) on the BioHarmony scale as a Substance → Pharmaceutical / Drug → Other Pharmaceutical.
What It Is
Retatrutide is an investigational once-weekly injectable peptide from Eli Lilly that simultaneously activates three metabolic receptors: GLP-1, GIP, and glucagon. The glucagon arm adds a thermogenic and hepatic-fat-oxidizing axis that dual agonists like tirzepatide do not have, which is why Phase 2 data shows the largest short-term weight loss of any outpatient drug class. But the compound has only ~700 published participants, a 48-week maximum exposure window, 100% Lilly-funded evidence with zero independent replication, and a real-world supply that is entirely unregulated gray-market research peptide with documented contamination.
Type: Peptide pharmaceutical (triple GLP-1/GIP/glucagon agonist; gray-market / investigational).
Current status: Investigational only as of April 2026. Not FDA approved. Phase 3 TRIUMPH program enrolling, with primary obesity readout from TRIUMPH-1 (NCT05929066) expected 2026 and cardiovascular outcomes 2027 to 2028. No legitimate pharmacy channel exists. All non-trial use is research-peptide grade.
Terminology
- GLP-1 (glucagon-like peptide-1): Gut hormone that triggers insulin release, suppresses glucagon, and slows gastric emptying. The backbone of the incretin class.
- GIP (glucose-dependent insulinotropic polypeptide): Second incretin hormone that amplifies GLP-1 insulin action and increases energy expenditure through adipose signaling.
- Glucagon receptor (GCGR): Hepatic receptor that normally drives glucose output. When activated alongside GLP-1/GIP (which offset hyperglycemia), it produces net fat oxidation and thermogenesis without raising blood sugar.
- GLP-1RA (GLP-1 receptor agonist): Drug class that mimics GLP-1 action. Includes semaglutide, liraglutide, and dulaglutide.
- TRIUMPH: Lilly's Phase 3 development program for retatrutide, covering obesity, T2D, MASH, obstructive sleep apnea, and cardiovascular outcomes.
- HbA1c: Glycated hemoglobin, a 3-month average of blood glucose. The primary efficacy endpoint in T2D trials.
- MACE (major adverse cardiovascular events): Composite endpoint of cardiovascular death, non-fatal MI, and non-fatal stroke used in outcomes trials.
- MASH (metabolic dysfunction-associated steatohepatitis): Modern term for NASH. Liver inflammation and fibrosis driven by metabolic dysfunction, now a primary Phase 3 target.
- NOAEL (no observed adverse effect level): Highest preclinical dose with no toxicity signal. Used to set first-in-human starting doses.
- BMI (body mass index): Weight-for-height screening metric. Primary inclusion criterion in obesity trials (typically BMI >=30 or >=27 with comorbidity).
- SURMOUNT: Lilly's Phase 3 program for tirzepatide in obesity.
- STEP: Novo Nordisk's Phase 3 program for semaglutide in obesity (Wegovy).
- FDA IND (investigational new drug): FDA clearance to run clinical trials on a compound not yet approved. Retatrutide is under active IND with Lilly.
- Gray-market: Product sold outside regulated pharmacy channels. For retatrutide, this means research-peptide grade material marketed "for research use only."
- Compounded: Pharmacy-prepared version of an approved drug. Semaglutide and tirzepatide have had compounded paths during shortages; retatrutide does not because it has no approved reference product.
Dosing & Protocols
Dosing information is summarized from published research and community reports. This is not a prescribing guide. Consult a healthcare provider before starting any protocol.
View 1 route and 3 protocols
Routes & Forms
| Route | Form | Clinical Range | Community Range |
|---|---|---|---|
| Subcutaneous (gray-market / investigational) | Reconstituted research peptide, weekly injection | 2 mg to 12 mg weekly (Phase 2/3 titration) Titrated up every 4 weeks in Lilly Phase 2/3. Not FDA approved. Supply in trials is Lilly-manufactured. | 0.5 mg to 12 mg weekly; some users exceed 12 mg Gray-market research peptide. Documented endotoxin contamination, identity failures, and mass variance of ±50% in independent testing. No compounding-pharmacy path exists. |
Protocols
Weight management titration (Phase 2/3) Clinical
- Dose
- 2 mg, then 4 mg, then 8 mg, then 12 mg subcutaneous weekly, stepping every 4 weeks over 12 to 20 weeks
- Frequency
- weekly
- Duration
- continuous
Jastreboff NEJM 2023 Phase 2 showed 24.2% weight loss at 48 weeks at the 12 mg dose.
Type 2 diabetes management (Phase 2) Clinical
- Dose
- Same titration to 4 mg to 12 mg target, chosen by response
- Frequency
- weekly
- Duration
- continuous
Rosenstock Lancet 2023: HbA1c -2.02% at 48 weeks, comparable to or exceeding semaglutide and tirzepatide.
MASLD/MASH management (Phase 2) Clinical
- Dose
- 12 mg weekly after titration
- Frequency
- weekly
- Duration
- 48 weeks studied
Sanyal Nat Med 2024: -82.4% relative liver fat, 86% MASLD resolution.
How this score is calculated →
Upside (2.67 / 5.00)
| Dimension | Weight | Score | Visual | Weighted |
|---|---|---|---|---|
| Efficacy | 25% | 4.9 | 1.225 | |
| Breadth of Benefits | 15% | 3.8 | 0.570 | |
| Evidence Quality | 25% | 2.5 | 0.625 | |
| Speed of Onset | 10% | 3.8 | 0.380 | |
| Durability | 10% | 1.5 | 0.150 | |
| Bioindividuality Upside | 15% | 4.8 | 0.720 | |
| Total | 3.670 |
Upside Rationale
Efficacy (4.9/5.0): Jastreboff NEJM 2023 Phase 2: -24.2% body weight at 48 weeks at the 12 mg dose, curve still descending, no plateau reached. HbA1c -2.02% in T2D (Rosenstock, Lancet 2023). Liver fat -82.4% relative at 12 mg (Sanyal, Nat Med 2024) with 86% achieving complete MASLD resolution. Systolic BP -8 mmHg, triglycerides -25 to -35%. Cohen's d clears 1.0 for weight. Unprecedented magnitude in the outpatient drug class and substantially higher than semaglutide (~15%) or tirzepatide (~21%) at comparable timepoints. This is the single strongest dimension of the entire profile.
Breadth of benefits (3.8/5.0): Demonstrated benefits span weight, glycemia, liver fat, blood pressure, and lipids in the Phase 2 program. Cardiovascular hard endpoints are not yet reported: TRIUMPH-OUTCOMES (NCT05882045) reads 2027 to 2028. Kidney outcomes are unmeasured. Addiction and cognition signals have not been studied in humans. Proven breadth is narrower than semaglutide (which has SELECT CV outcomes data) until Phase 3 delivers. Indicated populations currently trial-only: obesity, T2D, MASLD/MASH, and obstructive sleep apnea.
Evidence quality (2.5/5.0): Only 3 published Phase 2 RCTs plus one Phase 1, approximately 700 total participants dosed, maximum 48-week exposure window. 100% Lilly-funded with zero independent replication. No cardiovascular outcomes trial completed. No kidney outcomes. No post-marketing pharmacovigilance because the drug has not been marketed. A -1.0 integrity penalty applies for industry-only funding without replication, the standard discount for novel-mechanism drugs that have not yet survived external scrutiny.
Speed of onset (3.8/5.0): Appetite suppression within 1 to 2 weeks, which is the class effect across all GLP-1-containing agonists. Weight loss is approximately linear through week 24, then continues to accumulate through week 48 without plateau at the 12 mg dose. HbA1c drops within 4 to 8 weeks. Liver fat near-maximal by week 48 (Sanyal Nat Med 2024). Users feel GI tolerability effects immediately; measurable benefits follow within the first month.
Durability (1.5/5.0): Zero published off-drug data exists for retatrutide. The one piece of reasoning available is extrapolation from semaglutide's STEP 1 extension, which showed approximately two-thirds regain within 12 months of discontinuation. Retatrutide's steeper weight loss trajectory likely implies a steeper regain curve. This is a structural weakness of the entire incretin class: effect is conditional on continued dosing. Plan on indefinite therapy for metabolic disease indications or fast rebound for cosmetic use.
Bioindividuality upside (4.8/5.0): Response rates at therapeutic dose are essentially universal in Phase 2. 100% of 12 mg completers achieved >=5% weight loss. 83% hit >=15%. 63% hit >=20%. 26% hit >=30%. The responder curve is the broadest in the incretin class, which means trial outcomes are unlikely to be driven by a non-responder tail. This is one dimension where the data we have is internally robust: almost everyone responds, and they respond large.
Downside (3.05 / 5.00)
| Dimension | Weight | Score | Visual | Weighted |
|---|---|---|---|---|
| Safety Risk | 30% | 4.0 | 1.200 | |
| Side Effect Profile | 15% | 3.3 | 0.495 | |
| Financial Cost | 5% | 3.8 | 0.190 | |
| Time/Effort Burden | 5% | 1.5 | 0.075 | |
| Opportunity Cost | 5% | 2.2 | 0.110 | |
| Dependency / Withdrawal | 15% | 4.0 | 0.600 | |
| Reversibility | 25% | 2.3 | 0.575 | |
| Total | 3.245 | |||
| Harm subtotal × 1.4 | 4.018 | |||
| Opportunity subtotal × 1.0 | 0.375 | |||
| Combined downside | 4.393 | |||
| Baseline offset (constant) | −1.340 | |||
| Effective downside penalty | 3.053 |
Downside Rationale
Safety risk (4.0/5.0): A catastrophic risk floor applies because class-level MTC rodent signal, pancreatitis class prior, and a novel glucagon arm unstudied beyond 48 weeks cannot be ruled out at current sample sizes. Resting heart rate rise of +6.7 bpm at 12 mg is the largest in the incretin class. Only approximately 700 participants and 48 weeks of exposure provide minimal statistical power to detect rare serious events (anything below 1% incidence is statistically invisible at this N). The intrinsic pharmacological profile warrants the floor; gray-market supply contamination is addressed separately in the verdict and is not double-counted here.
Side effect profile (3.3/5.0): Nausea approximately 45% at the 12 mg dose (highest in the incretin class), vomiting approximately 16%, diarrhea approximately 27%, and 6% discontinuation at top dose. Absolute lean mass loss is the largest in class (up to 6.5 kg in the Phase 2 body-composition substudy) simply because total weight loss is the largest. Resting heart rate increase is also largest in class. All GI effects are titration-sensitive, which is why the 4-week step-up schedule matters. Users who skip titration increase discontinuation risk substantially.
Financial cost (3.8/5.0): Current gray-market pricing runs $200 to $400 per month for research-peptide grade material. Post-FDA approval, pricing is likely to match or exceed tirzepatide ($1,000+ per month cash, with insurance coverage conditional on obesity or T2D diagnosis plus BMI thresholds). Compounded paths do not exist for retatrutide because it has no approved reference product, so the gap between gray-market and approved pricing will be wider than it was for semaglutide. Long-term cost over years is material: $12,000 to $15,000 annually is realistic post-launch.
Time/effort burden (1.5/5.0): Once-weekly subcutaneous injection. Negligible effort, identical to semaglutide or tirzepatide in administration. Injection sites rotate across abdomen, thigh, or upper arm. Users who reconstitute research peptide add approximately 5 minutes of setup on dose day for bacteriostatic water mixing and aseptic technique. In-trial users use pre-filled pens (for Lilly trial material), which removes reconstitution entirely. Burden is among the lowest of any weight-loss intervention.
Opportunity cost (2.2/5.0): Same behavioral crowd-out as other incretins: blunted food reward, attenuated training appetite, reduced protein intake unless actively managed, and a tendency to replace lifestyle effort with pharmacological effort. Moderate trade-off. Users who do not resistance train or maintain 1.6+ g/kg protein will lose lean mass disproportionately (see bh_down_side_effects). The drug is strongest when stacked with lifestyle rather than substituted for it, which requires active coaching most self-directed users do not get.
Dependency/withdrawal (4.0/5.0): Class-level rebound is assumed from semaglutide and tirzepatide precedent. Steeper loss likely means steeper regain. Completely unstudied for retatrutide specifically. No weaning or cycling protocols have clinical validation. Functional dependency is high: the compound works by modifying appetite and hepatic fat oxidation, and those effects disappear quickly once plasma levels drop below threshold. For chronic metabolic disease this is acceptable; for cosmetic weight loss it creates an indefinite commitment the user may not have understood at the start.
Reversibility (2.3/5.0): Most pharmacological effects reverse within weeks of discontinuation: appetite returns, gastric emptying normalizes, insulin sensitivity reverts. Class-level risks (gastroparesis, pancreatitis, rare thyroid signals) may persist but are individually rare. The less reversible piece is body composition: lean mass lost during rapid weight loss tends to return as fat mass on regain, producing a worse body composition post-cycle than pre-cycle. For anyone using retatrutide short-term without resistance training, reversibility is net-negative from a composition standpoint.
Verdict
✅ Best for: Patients in active TRIUMPH Phase 3 trials receiving Lilly-manufactured product with full adverse event monitoring. If retatrutide approves in late 2027 with a clean label, obese adults with MASH or T2D who have failed first-line interventions become the primary population.
❌ Avoid if: You have any thyroid, pancreatic, or cardiovascular history; you are treating this as a lifestyle recomp drug rather than a serious metabolic disease intervention; you are pregnant or of childbearing potential without contraception; you are not willing to resistance train and eat 1.6+ g/kg protein to protect lean mass through historic rates of weight loss.
⚠️ Supply chain warning: As of April 2026, retatrutide is not FDA approved and cannot be obtained through any legitimate pharmacy channel. Real-world use is entirely gray-market research peptide supply with documented quality issues including endotoxin contamination (~78% of samples exceeding limits by ~1000×), identity failures, and mass accuracy variations of ±50%. These supply risks are not reflected in the dimension scores above (which evaluate the compound itself), but they represent a separate and serious risk layer for anyone sourcing outside a clinical trial.
Use Case Breakdown
The overall BioHarmony score reflects the intervention's primary evidence profile. These subratings are independent assessments per use case.
| Use Case | Score | Summary |
|---|---|---|
| ✅ Metabolic Health | 8.5 | Triple agonism provides comprehensive metabolic improvement across glucose, lipids, and energy expenditure |
| ✅ Liver / Detoxification | 8.0 | Glucagon receptor agonism directly promotes hepatic fat oxidation; dramatic NAFLD improvement in trials |
| ✅ Blood Sugar / Glycemic Control | 8.0 | GLP-1/GIP dual action on insulin secretion plus glucagon-mediated hepatic glucose regulation |
| 💪 Body Composition / Fat Loss | 7.5 | Up to 24% weight loss in Phase 2; glucagon component may preserve lean mass better than GLP-1 alone |
| 👍 Cardiovascular | 6.0 | Metabolic improvements should translate to CV benefit but no dedicated CV outcomes trial yet |
| ⚖️ Hormonal / Endocrine | 5.5 | Normalizes insulin signaling; weight loss improves sex hormones in obese individuals |
| ⚖️ Anti-Inflammatory | 5.0 | Weight loss and metabolic improvement reduce systemic inflammation; limited direct data |
| ○ Bone / Joint Health | 4.5 | Weight loss reduces mechanical joint stress; glucagon's bone effects unknown |
| ○ Healthspan | 4.5 | Promising metabolic profile but only Phase 2 data; long-term safety unknown |
| ○ Chronic Pain Management | 4.0 | Weight loss reduces osteoarthritis and mechanical pain; no direct analgesic effect |
| ○ Geriatric / Aging Population | 4.0 | Metabolic benefits relevant to elderly but sarcopenia risk from weight loss; lean mass data pending |
| ○ Flexibility / Mobility | 3.5 | Significant weight loss improves functional mobility |
| ○ Respiratory | 3.5 | Weight loss improves pulmonary function and sleep apnea |
| ○ Acute Pain Relief | 3.5 | Weight-related pain relief; not an analgesic |
| ○ Sleep Quality | 3.5 | Weight loss may improve sleep apnea; no sleep-specific trial data |
| ○ Longevity / Lifespan | 3.0 | Too early to assess; no long-term outcome data beyond 48 weeks |
| ○ Endurance / Cardio | 3.0 | Weight loss improves relative fitness but caloric deficit may impair performance |
| ○ Energy / Fatigue | 3.0 | Glucagon is thermogenic but GI side effects and caloric deficit may reduce energy |
Frequently Asked Questions
How does retatrutide work and why does it produce more weight loss than semaglutide or tirzepatide?
Retatrutide simultaneously activates three receptors: GLP-1 (appetite suppression, insulin secretion), GIP (amplifies GLP-1 action, energy expenditure), and glucagon (hepatic fat oxidation, thermogenesis). Semaglutide hits GLP-1 only; tirzepatide hits GLP-1 plus GIP. Adding the glucagon arm drives fat loss through a distinct thermogenic axis rather than appetite alone, which explains the 24.2% weight loss at 12 mg, 48 weeks in Jastreboff NEJM 2023 (n=338) versus approximately 15% for semaglutide in STEP 1 and 21% for tirzepatide in SURMOUNT-1.
What are the approved clinical doses and realistic gray-market protocols?
There are no approved clinical doses. Retatrutide has no FDA approval as of April 2026. Phase 2 and 3 trial titration runs 2 mg, then 4 mg, then 8 mg, then 12 mg subcutaneous weekly, stepping up every 4 weeks. Real-world gray-market users replicate this schedule using reconstituted research peptide. Some skip titration or push past 12 mg weekly, which has zero published safety data. Biohacker microdosing at 0.5 to 2 mg weekly is entirely speculative. Every dosing decision outside a TRIUMPH trial carries compound-quality and dosing-accuracy risk beyond the molecule itself.
How does retatrutide efficacy actually compare to semaglutide and tirzepatide in head-to-head terms?
Retatrutide 12 mg delivered 24.2% weight loss at 48 weeks in Jastreboff Phase 2 NEJM 2023, the curve still descending. Tirzepatide 15 mg in SURMOUNT-1 hit approximately 20.9% at 72 weeks. Semaglutide 2.4 mg in STEP 1 produced approximately 14.9% at 68 weeks. HbA1c reduction in retatrutide T2D trials was -2.02% versus -2.0% for tirzepatide and -1.6% for semaglutide. No direct head-to-head trials exist yet. Effect-size advantage is real but rests on a fraction of the participant-years behind the approved drugs.
What safety signals have appeared in the Phase 2 data and which class risks carry over?
Phase 2 safety across approximately 700 participants over 48 weeks: nausea approximately 45% at 12 mg (highest in the incretin class), vomiting approximately 16%, diarrhea approximately 27%, 6% discontinuation at top dose, and resting heart rate rise of +6.7 bpm (largest in class). Class-level risks carry in full: rodent medullary thyroid carcinoma (MTC) signal, pancreatitis risk, gastroparesis, and potential retinopathy worsening with rapid glucose drops. Cardiovascular outcomes and rare serious events are statistically underpowered at this sample size and exposure. The novel glucagon arm has zero long-term human safety record.
Who should avoid retatrutide entirely?
Contraindications follow the incretin class plus investigational-compound logic. Avoid if you have personal or family history of medullary thyroid carcinoma or MEN2, history of pancreatitis, severe gastroparesis, active eating disorder, or significant cardiovascular disease without specialist oversight. Pregnancy and childbearing potential without reliable contraception are absolute excludes because the drug must be discontinued roughly 2 months pre-conception. Anyone unwilling to resistance train and consume 1.6+ g/kg protein daily should avoid because lean mass loss tracks total weight loss, which is historic in magnitude.
What is the expected timeline for effects, plateau, and off-drug regain?
Appetite suppression starts within 1 to 2 weeks. Weight loss runs approximately linear through week 24, with the 48-week curve still descending at 12 mg (no plateau reached in Phase 2). HbA1c and liver fat improvements are measurable by week 8 and approach maximum by week 48. Off-drug durability is entirely unstudied for retatrutide. Extrapolating from semaglutide STEP 1 extension (approximately two-thirds regain within 12 months off drug), the steeper retatrutide loss likely produces steeper regain. Plan on indefinite dosing if used for metabolic disease; plan on rebound if used for cosmetic weight loss.
Is gray-market retatrutide safe to source, and how does it differ from pharmacy-compounded semaglutide?
Retatrutide has no compounding-pharmacy path in the US because it is not on an FDA shortage list and lacks an approved reference product. All real-world supply is research-peptide grade. Independent testing has documented endotoxin contamination in roughly 78% of research-peptide GLP-1 samples (often 1,000x acceptable limits), identity mismatches, and mass accuracy variations up to ±50%. That is categorically different from compounded semaglutide produced under 503A/503B oversight, where identity and sterility are USP-verified. Sourcing retatrutide outside a TRIUMPH trial means accepting unknown compound quality, unknown dose, and possible endotoxin exposure.
Do biohacker microdoses make sense for longevity or metabolic tuning in healthy adults?
No. Microdose retatrutide for longevity has zero human evidence. The published therapeutic window starts at 2 mg weekly; below that, you have no pharmacokinetic, efficacy, or safety data. Healthy metabolically normal adults take on class-level risks (MTC signal, pancreatitis, gastroparesis) plus gray-market supply risks for a speculative benefit. If the goal is metabolic optimization without a weight-loss indication, diet composition, resistance training, Zone 2 cardio, and sleep architecture are vastly better-evidenced interventions. Retatrutide is a serious drug for serious metabolic disease, not a lifestyle recomp tool.
How This Score Could Change
BioHarmony scores are living assessments. New research, regulatory changes, or personal context can shift the score up or down. These are the most likely scenarios that would change this intervention's rating.
| Scenario | New Score | Tier |
|---|---|---|
| TRIUMPH-OUTCOMES 20%+ MACE reduction (Evidence 2.5 to 3.5, Breadth 3.8 to 4.3) | 5.1 / 10 | ⚖️ Neutral |
| FDA approves + 2yr clean safety (Evidence 2.5 to 4.0, Safety 4.0 to 3.5, Breadth 3.8 to 4.3) | 5.4 / 10 | ⚖️ Neutral |
| Phase 3 surfaces MTC or cardiac signal (Safety 4.0 to 5.0, Side effects 4.0 to 4.5) | 4.1 / 10 | ⚠️ Proceed with caution |
| FDA approval + 5yr clean safety + durability data (Evidence 2.5 to 4.5, Safety 4.0 to 3.5, Durability 1.5 to 2.5) | 5.7 / 10 | ⚖️ Neutral |
| Population: obese T2D with MASH only | 5.6 / 10 | ⚖️ Neutral |
Key Evidence Sources
- Jastreboff AM et al. (2023) Phase 2 obesity trial. NEJM. 24.2% weight loss at 48 weeks, 12 mg dose, n=338. PMID 37366315.
- Rosenstock J et al. (2023) Phase 2 T2D. Lancet. HbA1c -2.02% at 36 weeks. PMID 37356367.
- Sanyal AJ et al. (2024) Phase 2 MASLD. Nat Med. -82.4% relative liver fat, 86% MASLD resolution at 48 weeks. PMID 38858523.
- Coskun T et al. (2022) Preclinical pharmacology. Cell Metab. Triple agonist receptor binding and in vivo pharmacology. PMID 35914546.
- Urva S et al. (2022) Phase 1 single ascending dose. Lancet. First-in-human pharmacokinetics. PMID 35914548.
- Phase 2 body composition substudy (2025). Lancet Diab Endo. Lean mass loss characterized; glucagon arm partially preserves lean tissue relative to dual agonists. PMID 40609566.
- Systematic review and meta-analysis (2025). Pooled efficacy and tolerability across Phase 1/2 retatrutide trials. PMC12026077.
- TRIUMPH-1 Phase 3 obesity. Phase 3 obesity outcomes trial. Primary completion 2026.
- TRIUMPH-OUTCOMES CV trial. Dedicated cardiovascular outcomes trial. Primary readout 2027 to 2028.
- FDA safety communication on unapproved GLP-1 drugs. Agency warning on compounded and research-grade GLP-1 supply quality and identity failures.
Other interventions for Metabolic Health
See all ratings →📊 How BioHarmony scoring works
BioHarmony translates a weighted expected-value calculation into a reader-facing 0–10 score. 5.0 is neutral (benefits and risks balance). Above 5 = benefits outweigh risks; below 5 = risks outweigh benefits.
Harm-type downsides (safety risk, side effects, reversibility, dependency) carry a 1.4× precautionary multiplier. Harm weighs more than benefit. Opportunity-type downsides (financial cost, time/effort, opportunity cost) are subtracted at face value.
Use case subratings are independent assessments of how well the intervention addresses specific health goals. They are not components of the overall score. Each subrating reflects the scorer's judgment based on use-case-specific evidence, safety, and effect sizes.
Every dimension is evaluated on a 1–5 scale, and the baseline (1) is subtracted before weighting. A perfect intervention with zero downsides contributes zero penalty rather than a residual floor, so top-tier scores are actually reachable.
EV = Upside − Downside
EV = 2.670 − 3.053 = -0.383
EV ranges from −5 to +5. Adding 7 shifts to 2–12, dividing by 12 normalizes to 0–1, then ×10 gives the 0–10 score.
Score = ((-0.383 + 7) / 12) × 10 = 5.5 / 10
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