Metabolic and weight-loss compounds

Semaglutide

Also known as Ozempic, Wegovy, Rybelsus, Sema GLP-1

Plain-English version: A 31 amino acid analog of the gut hormone GLP-1, approved as a weight-loss and diabetes drug and also sold under invented names.

Strongest evidence, and what it covers [Human RCT] Weight reduction and cardiovascular events with an approved GLP-1 analog [1] [2] [3] [6]

Semaglutide is a 31 amino acid analog of glucagon-like peptide 1, the hormone the gut releases after eating that slows the stomach and signals fullness. The molecule is rebuilt to survive for days rather than minutes. The current injection label carries an initial United States approval year of 2017 [3].

STEP 1 randomised 1,961 adults with obesity and without diabetes to once-weekly semaglutide at 2.4 mg or to placebo for 68 weeks. Mean body-weight change at week 68 was -14.9 percent against -2.4 percent on placebo, with nausea and diarrhoea the most common adverse events [1].

SELECT randomised 17,604 adults with existing cardiovascular disease and no diabetes. A first cardiovascular event, meaning cardiovascular death, non-fatal heart attack or non-fatal stroke, occurred in 6.5 percent of the semaglutide arm and 8.0 percent of the placebo arm over a mean follow-up of 39.8 months. Permanent discontinuation for adverse events occurred in 16.6 percent against 8.2 percent on placebo [2].

Those are among the largest randomised comparisons in this catalog. What they do not settle is what a container sold under an invented name holds, which is a manufacturing question rather than a clinical one.

Where it stands Semaglutide is an approved prescription drug in the United States, with an initial approval year of 2017 on the current injection label [3]. FDA states on its unapproved GLP-1 page, current as of 15 June 2026, that it is aware of fraudulent compounded semaglutide marketed in the United States, and that it has warned companies illegally selling unapproved drugs containing semaglutide falsely labelled for research purposes or not for human consumption [6].

Our takeThis is the strongest evidence base on the site, and that is exactly why the useful question here is not whether the molecule was tested but whether a given container holds it.

Tirzepatide

Also known as Mounjaro, Zepbound, LY3298176, Tirz GLP-2

Plain-English version: A 39 amino acid molecule that acts at two gut hormone receptors at once, approved for weight loss and diabetes.

Strongest evidence, and what it covers [Human RCT] Weight reduction with an approved dual GIP and GLP-1 receptor agonist [4] [5] [6]

Tirzepatide is a 39 amino acid molecule built to activate two receptors at once: the GLP-1 receptor and the receptor for glucose-dependent insulinotropic polypeptide, a second hormone the gut releases after eating. The current weight-management label carries an initial United States approval year of 2022 [5].

SURMOUNT-1 randomised adults with obesity to once-weekly tirzepatide or placebo for 72 weeks. Mean body-weight change at week 72 was -15.0 percent in the 5 mg arm, -19.5 percent in the 10 mg arm and -20.9 percent in the 15 mg arm, against -3.1 percent on placebo. Half of the 10 mg arm and 57 percent of the 15 mg arm had a reduction of 20 percent or more, against 3 percent on placebo. Gastrointestinal adverse events were the most common, arose mainly while the amount given was being increased, and led to discontinuation in 4.3 to 7.1 percent of the tirzepatide arms against 2.6 percent on placebo [4].

The gap between that record and the gray market is the same as for semaglutide, and FDA describes it in the same document: compounded and falsely labelled versions of tirzepatide are among the products the agency has acted against [6].

Where it stands Tirzepatide is an approved prescription drug in the United States, with an initial approval year of 2022 on the current weight-management label [5]. FDA states that it is aware of fraudulent compounded tirzepatide marketed in the United States, and that it has warned companies illegally selling unapproved drugs containing tirzepatide falsely labelled for research purposes or not for human consumption, on a page current as of 15 June 2026 [6].

Our takeTwo receptors produced a larger mean change than one in separate trials, but no trial on this page randomised the two molecules against each other, so the comparison people make between them is a comparison across trials rather than within one.

Retatrutide

Also known as LY3437943, Reta GLP-3, GLP-3 RT

Plain-English version: A 39 amino acid molecule acting at three hormone receptors, still in trials and not approved anywhere.

Strongest evidence, and what it covers [Human RCT] Weight and blood-sugar change with an investigational triple receptor agonist [6] [7] [8] [9] [10]

Retatrutide is a 39 amino acid molecule that activates three receptors: GLP-1, GIP and glucagon. The glucagon arm is the design change. The stated rationale in the published phase 2 report is that glucagon receptor activation increases energy expenditure where the other two act mainly on intake [7], which is a description of the design rather than a measured result in the people who took it.

The phase 2 obesity trial randomised 338 adults across six retatrutide arms and placebo for 48 weeks. Mean body-weight change at week 48 ran from -8.7 percent in the 1 mg arm to -24.2 percent in the 12 mg arm, against -2.1 percent on placebo. Gastrointestinal events and heart rate both rose with the amount given [7]. A second phase 2 tested it in 281 people with type 2 diabetes [8].

TRANSCEND-T2D-1, the published phase 3, ran 40 weeks in 537 adults with type 2 diabetes. HbA1c, the standard blood-sugar measure, changed by -1.94 percent in the 12 mg arm against -0.81 percent on placebo, and body weight by -15.3 percent against -2.6 percent. Two deaths occurred, both in the 4 mg arm and both reported as unrelated to the study drug [9].

TRIUMPH-1, the obesity phase 3, is registered with 2,335 participants and shows as completed with no posted results and no indexed report [10]. The topline figures in circulation come from sponsor announcements, so this page does not restate them.

Where it stands Retatrutide is investigational and is not approved in any country. FDA states, on a page current as of 15 June 2026, that retatrutide cannot be used in compounding under federal law, that it is not a component of an approved drug, and that the agency has warned telehealth companies marketing it directly to consumers, active-ingredient distributors supplying it to compounders, and outsourcing facilities repackaging it [6].

Our takeThis has the deepest published trial record of any unapproved compound in the catalog, and the widest gap between what has been published and what is being quoted about it.

Cagrilintide

Also known as AM833, CagriSema (with semaglutide)

Plain-English version: A long-acting analog of amylin, a hormone released alongside insulin, studied mostly in combination rather than alone.

Strongest evidence, and what it covers [Human RCT] Weight reduction with a long-acting amylin analog, alone and combined [6] [11] [12]

Cagrilintide is a long-acting analog of amylin, a pancreatic hormone released alongside insulin that slows stomach emptying and reduces food intake. It is the one compound on this page outside the GLP-1 family.

Alone it has one published dose-finding phase 2. It randomised 706 adults without diabetes across five cagrilintide arms, an active comparator and placebo, for 26 weeks. Mean weight reduction across the cagrilintide arms ran from 6.0 to 10.8 percent against 3.0 percent on placebo, with gastrointestinal disorders and administration-site reactions the most frequent adverse events, reported by 41 to 63 percent of cagrilintide participants against 32 percent on placebo [11].

Almost everything published since tests it combined with semaglutide. REDEFINE 1 randomised 3,417 adults, of whom 302 received cagrilintide alone and 2,108 received the combination; the combination arm changed by -20.4 percent at week 68 against -3.0 percent on placebo, and gastrointestinal adverse events affected 79.6 percent of that arm against 39.9 percent on placebo [12].

The large published numbers therefore belong to a two-molecule product, and the question a reader arrives with, what cagrilintide alone does over a long period, has a 26-week answer and no phase 3 answer.

Where it stands Cagrilintide is investigational and is not approved in any country. FDA states, on a page current as of 15 June 2026, that cagrilintide cannot be used in compounding under federal law and that it is not a component of an approved drug [6].

Our takeA compound whose headline figures were earned by a combination product is a compound whose headline figures are not about it.

Survodutide

Also known as BI 456906

Plain-English version: A molecule acting at two hormone receptors, GLP-1 and glucagon, in late-stage trials.

Strongest evidence, and what it covers [Human RCT] Weight reduction with an investigational glucagon and GLP-1 dual agonist [13] [14]

Survodutide activates the GLP-1 receptor and the glucagon receptor together, pairing a different second receptor with GLP-1 than tirzepatide does.

The dose-finding phase 2 randomised 387 adults with a body-mass index of at least 27 and without diabetes to four survodutide arms or placebo for 46 weeks. Mean body-weight change at week 46 ran from -6.2 percent in the lowest arm to -14.9 percent in the highest, against -2.8 percent on placebo. Adverse events occurred in 91 percent of survodutide recipients against 75 percent on placebo, and only 60.4 percent completed the treatment period [13].

SYNCHRONIZE-1, the phase 3, randomised 725 adults with obesity and without diabetes across two survodutide arms and placebo for 76 weeks. Under the trial's designated primary analysis rule, mean body-weight change at week 76 was -12.2 and -13.0 percent in the survodutide arms against -5.4 percent on placebo. Gastrointestinal symptoms were reported by 80.9 and 89.7 percent of those arms against 47.9 percent on placebo, and no deaths were reported [14].

Conference presentations of this programme have circulated larger percentage figures than the paper reports. A trial can be summarised under more than one analysis rule, and where they differ this page uses the published paper.

Where it stands Survodutide is investigational and is not approved in any country. Its phase 3 obesity trial is registered on ClinicalTrials.gov as NCT06066515 and was published in full in 2026 [14].

Our takeThe most under-covered compound on this page relative to what has actually been published about it, and the placebo arm in its phase 3 lost more weight than the placebo arm in any other trial here.

AOD-9604

Also known as Anti-obesity drug 9604, hGH fragment 176-191

Plain-English version: The tail end of human growth hormone, sold for fat loss after its own development program was abandoned.

Strongest evidence, and what it covers [Animal] Fat handling and body weight with a growth hormone fragment [15] [16] [17]

AOD-9604 is a synthetic copy of the last stretch of human growth hormone, residues 176 to 191. The parent hormone is 191 amino acids long and has a large clinical record, and that record belongs to the parent: nothing in it tested the fragment.

The published work on the fragment is animal work. In obese Zucker rats given AOD-9604 by mouth at 500 micrograms per kilogram of body weight over 19 days, body-weight gain was about 16 g against about 36 g in controls, and fat tissue from treated animals showed a higher rate of fat breakdown [15]. A second study compared it against intact growth hormone in obese mice [16].

The human side is empty in a checkable way. No trial of AOD-9604 under any spelling appears on ClinicalTrials.gov, searched on 2 August 2026. Accounts of a phase 2 programme that ended in 2007 circulate, but they trace to company announcements rather than to a registry entry or a published paper, so this page does not restate their figures.

The other claim attached to this compound is a GRAS status, meaning generally recognised as safe. FDA's GRAS Notice Inventory returned no records for AOD9604 when searched on 2 August 2026 [17], and a GRAS determination is a food-ingredient judgement rather than a finding of efficacy.

Where it stands AOD-9604 is not an approved drug in the United States, and no marketing application for it appears in the public record. A search of the FDA GRAS Notice Inventory for AOD9604 on 2 August 2026 returned no records [17].

Our takeThe gap here is not between weak human evidence and strong human evidence, it is between rodent studies and nothing, and the marketing rests on a parent molecule's file and a food-ingredient status that the agency's own inventory does not show.

Tesofensine

Also known as NS2330

Plain-English version: Not a peptide. A small molecule that blocks the reuptake of three brain chemicals, repurposed for weight loss after failing in Alzheimer's and Parkinson's.

Strongest evidence, and what it covers [Human RCT] Weight reduction with a triple monoamine reuptake inhibitor [18] [19] [20] [21] [22]

Tesofensine is not a peptide. It is a small molecule, originally coded NS2330, that blocks the reuptake of three chemical messengers in the brain: noradrenaline, dopamine and serotonin. It was developed first as a treatment for Alzheimer's disease and for Parkinson's disease.

Weight loss appeared in that programme as a side finding, and the pooled analysis of it is published. Four randomised, double-blind, multicentre trials in those two diseases were combined, 740 participants on tesofensine and 228 on placebo, given by mouth for 14 weeks with no weight-loss programme attached. Weight change across the whole cohort ran from a gain of 0.5 percent on placebo to a loss of 2.8 percent in the highest arm. Heart rate rose by up to 6.8 beats per minute against placebo, with no measured change in blood pressure [19]. On that basis the compound was redirected at obesity.

The obesity trial is a phase 2 run at five Danish centres. After a two-week run-in, 203 adults with a body-mass index between 30 and 40 were placed on an energy-restricted diet and randomised to one of three tesofensine arms or to placebo for 24 weeks. Mean weight change was -4.5, -9.2 and -10.6 percent across the three arms, against -2.0 percent on diet and placebo. Dry mouth, nausea, constipation, hard stools, diarrhoea and insomnia were the most common adverse events, and heart rate rose by 7.4 beats per minute in the middle arm [18].

That paper carries an editorial mark, and it belongs on this page rather than in a footnote. The Lancet published an expression of concern about the trial in April 2013 [20]. The trial's authors published a reply in July 2013 under the heading under-reporting of adverse effects of tesofensine [21]. The paper has not been retracted, and the expression of concern has not been withdrawn. Anyone quoting the 10.6 percent figure is quoting a paper in that state.

The registry record stops at phase 2. A ClinicalTrials.gov search for tesofensine as an intervention on 2 August 2026 returned 13 studies, every one of them phase 1 or phase 2, two of them withdrawn with nobody enrolled, and none of them phase 3 [22]. Several of the later ones test tesofensine combined with metoprolol, a beta blocker, in rare conditions rather than in general obesity.

Where it stands Tesofensine has never been approved in the United States and no phase 3 trial of it is registered on ClinicalTrials.gov, searched on 2 August 2026 [22]. Reports of a regulatory decision in Mexico circulate widely; this page has not traced one to a primary agency document, and so does not state one.

Our takeA real randomised trial with a real result, published in a major journal, that a reader still cannot take at face value, because the journal itself said so and the authors' reply was about adverse-event reporting.

Mazdutide

Also known as IBI362, LY3305677

Plain-English version: A molecule acting at two hormone receptors, GLP-1 and glucagon, approved in China and not approved in the United States.

Strongest evidence, and what it covers [Human RCT] Weight reduction with a dual glucagon and GLP-1 receptor agonist approved in China [23] [24]

Mazdutide activates the GLP-1 receptor and the glucagon receptor, the same pair as survodutide, under the development codes IBI362 and LY3305677.

One thing should be said before the evidence. This site has not run its own source review of mazdutide, and this entry reports only what sits on the public record as of 2 August 2026. Where the other entries on this page draw on a full read of a literature, this one draws on a registry, two published trials and a regulatory review.

That record is larger than the catalog note behind this page suggested. GLORY-1 was a phase 3 trial conducted in China. It randomised 610 adults who had a body-mass index of at least 28, or of at least 24 with a weight-related condition, to one of two mazdutide arms or to placebo for 48 weeks. Mean body-weight change at week 32, the trial's primary time point, was -10.09 percent in the 4 mg arm and -12.55 percent in the 6 mg arm against a gain of 0.45 percent on placebo. At week 48 the figures were -11.00 percent, -14.01 percent and a gain of 0.30 percent. Gastrointestinal events were the most frequently reported adverse events, and stopping the trial regimen for an adverse event occurred in 1.5 percent, 0.5 percent and 1.0 percent of the three arms [23].

The regulatory outcome is documented in a drug-approval review published in 2025. Mazdutide received its first approval in China in June 2025, for long-term weight management in adults meeting those body-mass index thresholds alongside diet and activity, and a second Chinese approval in September 2025 for blood-sugar control in type 2 diabetes [24].

Two consequences follow, and both are the sort of thing that gets lost in the retelling. An approval in one country is not an approval in another, and mazdutide has no United States approval. And an approval anywhere says nothing about the contents of a container bought outside a pharmacy, which is a manufacturing question rather than a clinical one.

Where it stands Mazdutide received its first regulatory approval in China in June 2025 for long-term weight management, and a further Chinese approval in September 2025 for glycaemic control in type 2 diabetes, as recorded in a 2025 drug-approval review [24]. It is not approved in the United States.

Our takeThe most complete trial record on this page that almost no English-language source covers, and the one place where this site is reporting a public record rather than a review it has done itself.