Research Journal
An editorial evidence library. We summarise the trials that this field cites, state what each one actually found, and — the part usually missing — state what it does not prove.
This is not a peer-reviewed academic journal. It is an editorial evidence library: structured summaries of the primary literature, written so that a non-specialist can see exactly how far a result stretches and where it stops. Every entry names the funder, the design, the population, and the boundary of the evidence. We do not invent citations, DOIs or results.
Study summaries
SURMOUNT-1
SURMOUNT-1: tirzepatide once weekly for the treatment of obesity…
New England Journal of Medicine · June 2022
SURMOUNT-5
SURMOUNT-5: tirzepatide as compared with semaglutide for the treatment of obesity…
New England Journal of Medicine · May 2025
STEP-1
STEP 1: once-weekly semaglutide in adults with overweight or obesity…
New England Journal of Medicine · March 2021
SELECT
SELECT: semaglutide and cardiovascular outcomes in obesity without diabetes…
New England Journal of Medicine · December 2023
Also in the Research Journal
Why every entry has a "what this does not prove" section
| Trial | Arm | Result | Duration | Comparator | Source |
|---|---|---|---|---|---|
| SURMOUNT-1 | Tirzepatide 15 mg | −20.9% | 72 weeks | Placebo −3.1% | NEJM 2022 (Jastreboff et al.) |
| SURMOUNT-1 | Tirzepatide 10 mg | −19.5% | 72 weeks | NEJM 2022 | |
| SURMOUNT-1 | Tirzepatide 5 mg | −15.0% | 72 weeks | NEJM 2022 | |
| SURMOUNT-5 | Tirzepatide (max tolerated) | −20.2% | 72 weeks | vs semaglutide −13.7% | NEJM 2025 (Aronne et al.) |
| STEP 1 | Semaglutide 2.4 mg | −14.9% | 68 weeks | Placebo −2.4% | NEJM 2021 (Wilding et al.) |
| STEP 8 | Semaglutide 2.4 mg | −15.8% | 68 weeks | vs liraglutide 3.0 mg −6.4% | JAMA 2022 (Rubino et al.) |
| SCALE | Liraglutide 3.0 mg | −8.0% | 56 weeks | Placebo −2.6% | NEJM 2015 |
| SELECT | Semaglutide 2.4 mg | 20% MACE reduction | ~40 months | Cardiovascular outcomes | NEJM 2023 |
What we verify, and what we do not
Two claims on any telehealth page look identical and are not. "This provider uses a licensed pharmacy" may mean we checked a state board database, or it may mean the provider said so. Those are different epistemic states and we label them differently.
| Label | Means | Example |
|---|---|---|
| Verified | We hold a dated capture or a primary-source confirmation | LillyDirect's $299 — from Lilly's own pricing page |
| Reported — pending verification | A provider or third party reports it; we have NOT captured it ourselves | Competitor prices from the July 2026 dataset; every pharmacy relationship on this site |
| Evaluation in progress | Verification pending. We are not asserting the fact at all | Cancellation terms we could not obtain in writing |
We do not upgrade a price to Verified because another comparison site published it. Sites in this category contradict each other routinely — the dataset behind this site corrected a stored TrimRx figure of $259 that matched no current tier, and an Eden brand-Zepbound figure of $299 that was actually LillyDirect's price rather than Eden's real $1,399. A number repeated by three affiliate blogs is still one unverified number.
Three facts that apply to everything in this section
Brand prices collapsed, and most comparison pages have not updated. Brand Zepbound is $299-$449 through LillyDirect. Brand Wegovy is $349 through NovoCare, and the oral Wegovy tablet is $149. Foundayo, Lilly's approved oral GLP-1, starts at $149. With commercial coverage either brand can be roughly $25 a month. Against that, a compounded programme priced above $299 is charging more than the FDA-approved drug — and several are.
The legal basis for compounding narrowed sharply in 2025. The FDA declared both shortages resolved and enforcement discretion ended for every class of compounder between February and May 2025. The surviving route requires a prescriber to document a clinical difference for the individual patient — which is what "personalized dosing" and "microdose" programmes are, as a matter of regulatory mechanics rather than clinical innovation.
The trial evidence applies to injections. Every efficacy figure in this field — SURMOUNT, STEP, SELECT — comes from an FDA-approved subcutaneous injection. None of it was collected on a compounded preparation, a microdose, or an orally disintegrating tablet. The evidence is strong exactly where it was gathered and silent everywhere else, and the gap between those two things is where most of the marketing in this industry operates.
Questions to ask about the pharmacy
The pharmacy matters more than the telehealth brand on the front of the website. The telehealth company arranges the consultation; the pharmacy makes the medicine you inject.
- Which specific pharmacy will fill my prescription? Not "our network" — the name of the facility.
- Is it a 503A state-licensed pharmacy or a 503B FDA-registered outsourcing facility? These are different regulatory categories with different oversight, and a company can use both for different products.
- In which state is it licensed, and can I look up the licence? State boards of pharmacy publish licensee databases.
- What is the exact salt form and concentration? Semaglutide sodium and semaglutide acetate are not the same active ingredient as the semaglutide base in approved products, and the FDA has said they are not appropriate for compounding.
- Is the vial single-dose or multi-dose? A multi-dose vial requires you to measure each dose yourself, which is the most common source of the dosing errors behind reported adverse events.
- Will you provide a certificate of analysis?
- Has the pharmacy received any FDA warning letter or state board action?
A provider that answers all seven in writing is demonstrating something real. A provider that will not name its pharmacy has given you an answer, whether it intended to or not.
How we grade evidence
| Tier | Source type | How we treat it |
|---|---|---|
| 1 | FDA labels, safety communications, official guidance | Authoritative for regulatory status |
| 2 | Randomised controlled trials in PubMed-indexed journals | Primary evidence for efficacy |
| 3 | Systematic reviews and meta-analyses | Strongest for synthesis |
| 4 | ClinicalTrials.gov registrations | For design and status; not results |
| 5 | Professional society guidelines | For standard of care |
| 6 | Government sources (CDC, CMS, NPI registry, state boards) | For verification of entities |
| 7 | Provider's own pages | For that provider's prices and claims ONLY |
| — | Reddit, forums, patient anecdote | Never as evidence of price, safety or efficacy. Labelled as anecdote if cited at all |
| — | Affiliate comparison sites | Never as proof of a medical claim. A price they publish is Reported, not Verified |
| — | Animal studies | Never as proof of human clinical effect |
Jastreboff AM et al., N Engl J Med 2022 (NCT04184622), n=2,539. Dose-response is real: the effect rises with dose. These are FDA-APPROVED SUBCUTANEOUS INJECTION doses — they do not transfer to compounded, microdose or ODT products. Trial means are not individual promises.
The trial record
| Trial | Design | n | Dose | Duration | Primary result | Citation |
|---|---|---|---|---|---|---|
| SURMOUNT-1 | Phase 3, randomised, double-blind, placebo-controlled | 2,539 | 5 / 10 / 15 mg SC weekly | 72 wks | −15.0% / −19.5% / −20.9% vs −3.1% placebo | Jastreboff, NEJM 2022; NCT04184622 |
| SURMOUNT-2 | Phase 3, RCT, in type 2 diabetes | 938 | 10 / 15 mg SC weekly | 72 wks | −12.8% / −14.7% vs −3.2% placebo | Garvey, Lancet 2023; NCT04657003 |
| SURMOUNT-3 | Phase 3, RCT, after 12-wk intensive lifestyle lead-in | 806 | Max tolerated (10/15 mg) | 72 wks | −18.4% additional, vs +2.5% placebo | Wadden, Nat Med 2023; NCT04657016 |
| SURMOUNT-4 | Randomised WITHDRAWAL after 36-wk open-label lead-in | 670 | Max tolerated | 88 wks | Continue: −5.5% further. Withdraw to placebo: +14.0% REGAINED | Aronne, JAMA 2024; NCT04660643 |
| SURMOUNT-5 | Phase 3b, OPEN-LABEL, active-controlled head-to-head | 751 | Max tolerated vs semaglutide | 72 wks | −20.2% vs semaglutide −13.7%, p<0.001 | Aronne, NEJM 2025; NCT05822830 |
| SURPASS-2 | Phase 3, RCT, type 2 diabetes, active-controlled | 1,879 | 5 / 10 / 15 mg vs semaglutide 1 mg | 40 wks | HbA1c −2.01 to −2.30% vs −1.86% | Frías, NEJM 2021; NCT03987919 |
| SURPASS-CVOT | Phase 3, cardiovascular outcomes, vs dulaglutide | 13,299 | Max tolerated | ~4.5 yrs | Non-inferior for MACE; not superiority vs placebo | Nicholls, 2024; NCT04255433 |
1. They are means, not promises. A −20.9% mean in SURMOUNT-1 contains people who lost far more and people who lost almost nothing. A trial average tells you what happened to a population; it does not tell you what will happen to you.
2. Every one is an FDA-APPROVED SUBCUTANEOUS INJECTION. No trial in this table tested a compounded preparation, a microdose regimen, or an orally disintegrating tablet. When these figures appear on a page selling a compounded ODT, evidence has been moved across a dosage form without justification.
3. All were funded by Eli Lilly, which manufactures tirzepatide. That is normal in drug development and does not make the results false — these are large, peer-reviewed studies. It belongs in the citation anyway, and it matters most in SURMOUNT-5, where the funder made the winning drug and the trial was open-label.
Jastreboff AM et al., N Engl J Med 2022, n=2,539 (NCT04184622). The effect rises with dose — which is precisely why a ~1mg 'microdose' cannot be expected to produce the headline result. FDA-approved subcutaneous injection.
The evidence is strong exactly where it was gathered and silent everywhere else. The gap between those two things is where most of the marketing in this industry operates, and recognising it is the single most useful skill a patient in this market can have.
Dosing, titration, and what it does to your bill
| Period | Dose | What it is for |
|---|---|---|
| Weeks 1–4 | 2.5 mg | Tolerance-building only. This dose is not intended to produce weight loss. If your provider's price is quoted at 2.5 mg, that is not the price of treatment. |
| Weeks 5–8 | 5 mg | First therapeutic dose (−15.0% in SURMOUNT-1). |
| Weeks 9–12 | 7.5 mg | Escalate only if tolerated. |
| Weeks 13–16 | 10 mg | A common maintenance dose (−19.5%). |
| Weeks 17–20 | 12.5 mg | Escalate only if tolerated. |
| Week 21+ | 15 mg | Maximum maintenance dose (−20.9%). |
The advertised price is usually the 2.5 mg price. On a programme that escalates with dose, the rate you are quoted at signup is for a dose the label explicitly describes as a starting dose — not a treatment dose. Ask what you will pay at 10 mg, and compare that number instead.
A 'microdose' of ~1 mg/week sits below every dose in SURMOUNT. The trials used 5, 10 and 15 mg. A microdose is not a discounted route to the SURMOUNT result; it is a different product with a smaller expected effect and no equivalent trial evidence.
Safety, contraindications and monitoring
Tirzepatide carries a boxed warning for thyroid C-cell tumours, based on rodent data. It is contraindicated in anyone with a personal or family history of medullary thyroid carcinoma or Multiple Endocrine Neoplasia syndrome type 2. This is not a precaution to weigh; it is a hard stop.
Serious but less common risks include pancreatitis, gallbladder disease (cholelithiasis and cholecystitis), acute kidney injury secondary to dehydration from vomiting or diarrhoea, diabetic retinopathy complications in people with existing retinopathy, and hypoglycaemia when combined with insulin or a sulfonylurea. Severe abdominal pain radiating to the back warrants urgent assessment for pancreatitis, not a message to a chat widget.
Before starting, a clinician should establish a baseline: weight and BMI, blood pressure, HbA1c or fasting glucose, a lipid panel, and renal and hepatic function. During treatment, tolerance should be reviewed at each escalation step rather than escalated automatically on a calendar.
Percentage of participants reporting each event. Gastrointestinal effects dominate, are usually mild-to-moderate, and are most pronounced during dose escalation. Source: SURMOUNT-1, N Engl J Med 2022.
Discontinuation: what the withdrawal trial found
Aronne LJ et al., JAMA 2024, n=670 (NCT04660643). After a 36-week open-label lead-in, participants randomised to placebo regained ~14% of body weight over the following 52 weeks; those who continued lost a further ~5%. This is the single most important trial for understanding the true cost of treatment.
In SURMOUNT-4 — the randomised withdrawal trial — participants taken off tirzepatide after a 36-week lead-in regained roughly 14% of body weight over the following year, while those who continued lost a further ~5%. This is the trial that most changes the arithmetic of treatment, and it is almost never cited on a pricing page.
The consequence is financial as much as clinical. If holding the result requires holding the medication, then the figure that matters is not the introductory price, and not even the annual price. It is the indefinite monthly price. Anyone selecting a provider on the strength of a first-month rate is optimising the wrong variable entirely.
Questions to ask your clinician
- Given my history — specifically thyroid, pancreatic and gallbladder — is a GLP-1 appropriate for me at all?
- What baseline laboratory work will you order before I start?
- What is my target dose, and how quickly will we escalate?
- Which side effects should make me call you rather than wait it out?
- What is the plan for maintenance, and what happens if I stop?
- Will I see the same clinician at each follow-up, or a different one each time?
Compounded, brand, microdose, ODT — four different products
These words are used interchangeably in marketing and they are not interchangeable at all. The distinction decides what evidence applies to what you are actually buying.
| Product | Regulatory status | Trial evidence |
|---|---|---|
| Brand Zepbound / Mounjaro (injection) | FDA-approved. Reviewed for safety, effectiveness and quality before marketing. | Direct. SURMOUNT and SURPASS tested exactly this product. |
| Brand Foundayo (oral, orforglipron) | FDA-approved. Its own trial programme. | Direct, for that product. |
| Compounded tirzepatide (injection, full dose) | NOT FDA-approved. No premarket review of safety, effectiveness or quality. | None for the compounded product itself. Same molecule, same route — but the product in your hand was never in a trial. |
| Microdose (~1 mg/wk) | NOT FDA-approved. | None. Sits BELOW every dose in SURMOUNT (5/10/15 mg). Expect a smaller effect. |
| ODT / oral compounded | NOT FDA-approved. | NONE. No trial has ever tested it. Oral bioavailability for these peptides is a real pharmacological problem and is unpublished for this product. |
The evidence is strong exactly where it was gathered and silent everywhere else. The gap between those two things is where most of the marketing in this industry operates, and recognising it is the single most useful skill a patient in this market can have.