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THE ORIGINAL-STUDY DESK

Keep the paper in view.

Read a study as a particular experiment rather than a vote for a molecule. These records preserve the design, comparator and research population before summarizing the finding. Open the original paper to examine the complete methods, analysis and disclosures.

Different follow-up periods, enrollment criteria and approaches to missing data can change the meaning of a result. Search the collection with a question in mind, and keep the limitation beside the number when taking notes or comparing reports.

18 selected original study records, with findings and limitations.

Showing 18 of 18 study records.

Semaglutide2021
Randomised trial

Once-Weekly Semaglutide in Adults with Overweight or Obesity (opens the original source in a new tab)

New England Journal of Medicine

Design
Phase 3, double-blind, randomised, placebo-controlled trial; 68 weeks. Both groups received a lifestyle intervention.
Population / setting
Adults with obesity, or overweight plus a weight-related condition, without diabetes.
Sample size
n = 1,961

What was observed
Mean body-weight change at week 68 was −14.9% with semaglutide versus −2.4% with placebo; the estimated difference was −12.4 percentage points (95% CI −13.4 to −11.5).

Keep in view
This is a group-average weight outcome in a defined population receiving trial support, not an individual prediction or a cardiovascular-outcome result. Gastrointestinal adverse events and treatment discontinuation must be considered. Funded by Novo Nordisk.

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Semaglutide2023
Randomised trial

Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes (opens the original source in a new tab)

New England Journal of Medicine

Design
Multicentre, double-blind, randomised, placebo-controlled cardiovascular-outcomes trial; mean follow-up 39.8 months.
Population / setting
Adults aged 45 or older with established cardiovascular disease and overweight or obesity, without diabetes.
Sample size
n = 17,604

What was observed
Cardiovascular death, nonfatal myocardial infarction or nonfatal stroke occurred in 6.5% with semaglutide and 8.0% with placebo (hazard ratio 0.80; 95% CI 0.72–0.90). Permanent discontinuation due to adverse events occurred in 16.6% versus 8.2%.

Keep in view
The result concerns secondary cardiovascular prevention in people with existing cardiovascular disease. It does not establish the same benefit in younger, low-risk people or for other peptides. The hazard ratio is not the absolute risk difference. Funded by Novo Nordisk.

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Semaglutide2021
Randomised trial

Effect of Continued Weekly Subcutaneous Semaglutide vs Placebo on Weight Loss Maintenance in Adults With Overweight or Obesity: The STEP 4 Randomized Clinical Trial (opens the original source in a new tab)

JAMA

Design
Randomised, double-blind withdrawal trial: a 20-week semaglutide run-in followed by 48 weeks of continued treatment or placebo.
Population / setting
Adults without diabetes who reached and tolerated the study maintenance regimen during run-in; 803 of 902 run-in participants were randomised.
Sample size
n = 803

What was observed
From week 20 to week 68, mean weight changed by −7.9% with continued semaglutide versus +6.9% after switching to placebo, a difference of −14.8 percentage points (95% CI −16.0 to −13.5). Lifestyle intervention continued in both groups.

Keep in view
This is an enriched withdrawal population that had already tolerated and responded to treatment. The percentages start at week 20, not original baseline, and do not describe an untreated new-start comparison. Funded by Novo Nordisk.

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Tirzepatide2022
Randomised trial

Tirzepatide Once Weekly for the Treatment of Obesity (opens the original source in a new tab)

New England Journal of Medicine

Design
Phase 3, double-blind, randomised, placebo-controlled trial; 72 weeks, with a lifestyle intervention.
Population / setting
Adults with obesity, or overweight plus a weight-related complication; diabetes was excluded.
Sample size
n = 2,539

What was observed
Under the treatment-regimen estimand, mean weight changes across the three tirzepatide groups were −15.0%, −19.5% and −20.9%, compared with −3.1% with placebo. Gastrointestinal events were the most common adverse events.

Keep in view
The percentages belong to different studied regimens and cannot be treated as every patient’s expected result. This trial did not compare tirzepatide directly with semaglutide or establish cardiovascular-event superiority. Funded by Eli Lilly.

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Tirzepatide2024
Randomised trial

Continued Treatment With Tirzepatide for Maintenance of Weight Reduction in Adults With Obesity: The SURMOUNT-4 Randomized Clinical Trial (opens the original source in a new tab)

JAMA

Design
Phase 3 randomised withdrawal trial: a 36-week open-label lead-in, then 52 weeks of double-blind continuation or placebo.
Population / setting
Adults with obesity, or overweight plus a weight-related complication, without diabetes; 670 of 783 lead-in participants were randomised.
Sample size
n = 670

What was observed
From week 36 to week 88, mean weight change was −5.5% with continued tirzepatide versus +14.0% after switching to placebo. At week 88, 89.5% versus 16.6% maintained at least 80% of their lead-in weight loss.

Keep in view
Participants had already completed and tolerated a treatment lead-in. These are continuation-versus-withdrawal findings, not a new-start trial; changes are measured from week 36. Published online in 2023 and in the 2024 JAMA issue. Funded by Eli Lilly.

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Tirzepatide / semaglutide2025
Randomised trial

Tirzepatide as Compared with Semaglutide for the Treatment of Obesity (opens the original source in a new tab)

New England Journal of Medicine

Design
Phase 3b, randomised, open-label, active-controlled trial; 72 weeks at the maximum tolerated study regimens.
Population / setting
Adults with obesity without type 2 diabetes.
Sample size
n = 751

What was observed
Mean weight change at week 72 was −20.2% with tirzepatide versus −13.7% with semaglutide. Mean waist-circumference change was −18.4 cm versus −13.0 cm. Both comparisons favoured tirzepatide (P<0.001).

Keep in view
This direct comparison was open-label and tested particular regimens in a specific population. Weight superiority does not establish superiority for cardiovascular events, every clinical outcome or every individual. Gastrointestinal adverse events were common. Funded by Eli Lilly.

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Tirzepatide2025
Human study

Body composition changes during weight reduction with tirzepatide in the SURMOUNT-1 study of adults with obesity or overweight (opens the original source in a new tab)

Diabetes, Obesity and Metabolism

Design
DXA body-composition substudy nested within the randomised SURMOUNT-1 trial; baseline-to-week-72 analysis with pooled tirzepatide groups.
Population / setting
The 160 participants with baseline and end-of-study DXA data: 124 receiving tirzepatide and 36 receiving placebo.
Sample size
n = 160

What was observed
Fat mass changed by −33.9% with tirzepatide versus −8.2% with placebo; lean mass changed by −10.9% versus −2.6%. Approximately three quarters of weight reduction was fat mass and one quarter lean mass in both groups.

Keep in view
This is a selected substudy, not the full trial population. DXA lean soft tissue is not identical to skeletal muscle or strength. Some subgroup analyses were post hoc. A published correction changes Figure 4’s axis unit from percent to kilograms; the overall results quoted here are unchanged.

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Retatrutide2023
Randomised trial

Triple-Hormone-Receptor Agonist Retatrutide for Obesity — A Phase 2 Trial (opens the original source in a new tab)

New England Journal of Medicine

Design
Phase 2, double-blind, randomised, placebo-controlled trial; 48 weeks. Primary endpoint at week 24.
Population / setting
Adults with obesity, or overweight plus at least one weight-related condition.
Sample size
n = 338

What was observed
The highest studied arm had mean weight change of −17.5% at the primary 24-week endpoint versus −1.6% with placebo. At the secondary 48-week endpoint, changes were −24.2% versus −2.1%. Gastrointestinal events and increases in heart rate were reported.

Keep in view
This phase 2 result estimates effects in the studied arms and population, not an approved indication or a long-term cardiovascular outcome. The frequently quoted 24.2% is a secondary 48-week result, not the primary endpoint. Funded by Eli Lilly.

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Retatrutide2026
Randomised trial

Retatrutide, a Triple Hormone Receptor Agonist, for Treatment of Obesity (opens the original source in a new tab)

New England Journal of Medicine

Design
Phase 3, double-blind, randomised, placebo-controlled trial; 80 weeks. Weight endpoints used a treatment-regimen intention-to-treat estimand.
Population / setting
Adults with obesity without diabetes; prespecified subgroups included participants with knee osteoarthritis or obstructive sleep apnoea.
Sample size
n = 2,339

What was observed
At week 80, mean weight changes were −17.6%, −23.7% and −25.0% in the three retatrutide groups versus −3.9% with placebo. The two higher groups differed from placebo by −19.8 and −21.0 percentage points. Gastrointestinal events were the most common adverse events.

Keep in view
These weight results are intention-to-treat estimates; the paper uses a different hybrid estimand for osteoarthritis and sleep-apnoea endpoints. This is not a head-to-head comparison with other medicines or evidence of multi-year safety. Publication is not marketing authorisation. Funded by Eli Lilly.

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CJC-1295 with DAC2006
Randomised trial

Prolonged stimulation of growth hormone and insulin-like growth factor I secretion by CJC-1295, a long-acting analog of GH-releasing hormone, in healthy adults (opens the original source in a new tab)

Journal of Clinical Endocrinology & Metabolism

Design
Two randomised, double-blind, placebo-controlled early pharmacology studies lasting 28 and 49 days.
Population / setting
Healthy adults aged 21–61; the indexed primary abstract does not state the enrolment count.
Sample size
Not specified in this summary; consult the paper.

What was observed
The investigators reported sustained, exposure-related increases in measured GH and IGF-I, with an estimated CJC-1295 half-life of 5.8–8.1 days. These were endocrine and pharmacokinetic findings, not demonstrated improvements in strength, recovery or longevity.

Keep in view
Small, short early studies with surrogate hormone endpoints do not establish a clinical benefit or long-term safety. The studied albumin-binding DAC molecule should not be treated as equivalent to products labelled “no DAC”. Enrolment is left unspecified rather than inferred from secondary accounts.

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Ipamorelin2014
Randomised trial

Prospective, randomized, controlled, proof-of-concept study of the ghrelin mimetic ipamorelin for the management of postoperative ileus in bowel resection patients (opens the original source in a new tab)

International Journal of Colorectal Disease

Design
Multicentre, double-blind, randomised, placebo-controlled phase 2 proof-of-concept trial after bowel resection.
Population / setting
Hospitalised adults undergoing small- or large-bowel resection. Of 117 enrolled patients, 114 formed the safety and modified intention-to-treat populations.
Sample size
n = 117

What was observed
Median time from the first study treatment to a tolerated standardised solid meal was 25.3 hours with ipamorelin versus 32.6 hours with placebo; the difference was not statistically significant (P=0.15). Treatment-emergent adverse events were reported in 87.5% versus 94.8%.

Keep in view
The investigated use was postoperative bowel recovery with an intravenous trial formulation, not muscle gain, sleep or athletic recovery. The numerical meal-tolerance difference did not establish efficacy, and these event counts do not demonstrate safety for other routes or populations.

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Thymosin beta-4 (full-length; RGN-259)2015
Randomised trial

Thymosin beta 4 ophthalmic solution for dry eye: a randomized, placebo-controlled, Phase II clinical trial conducted using the controlled adverse environment model (opens the original source in a new tab)

Clinical Ophthalmology

Design
Single-centre, double-masked, randomised, placebo-controlled phase 2 trial of an ophthalmic formulation; 28 days of treatment.
Population / setting
Adults with moderate-to-severe dry eye who qualified in a controlled adverse-environment challenge.
Sample size
n = 72

What was observed
Neither primary endpoint—ocular discomfort nor inferior corneal staining on day 29—differed significantly from placebo. Some secondary analyses favoured thymosin beta-4, including discomfort during the day-28 challenge and central/superior corneal staining.

Keep in view
Secondary and ad hoc signals do not turn missed primary endpoints into a confirmed positive trial. This short study investigated a full-length thymosin beta-4 eye-drop formulation, not the TB-500 fragment or systemic use for sports injuries.

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Elamipretide (SS-31)2023
Randomised trial

Efficacy and Safety of Elamipretide in Individuals With Primary Mitochondrial Myopathy: The MMPOWER-3 Randomized Clinical Trial (opens the original source in a new tab)

Neurology

Design
Phase 3, multicentre, double-blind, randomised, placebo-controlled trial; 24 weeks.
Population / setting
Adults with genetically confirmed primary mitochondrial myopathy; 109 were assigned to elamipretide and 109 to placebo.
Sample size
n = 218

What was observed
The trial did not meet either primary endpoint: six-minute walk distance or fatigue on the PMMSA scale. The between-group difference in walk-distance change was −3.2 m (95% CI −18.7 to 12.3; P=0.69).

Keep in view
The findings concern a heterogeneous genetic mitochondrial-myopathy population, not healthy people or every mitochondrial disorder. Exploratory genotype findings do not replace the negative prespecified primary analysis. These results should not be conflated with a separate Barth-syndrome indication.

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GHK-Cu1988
Preclinical

Stimulation of collagen synthesis in fibroblast cultures by the tripeptide-copper complex glycyl-L-histidyl-L-lysine-Cu2+ (opens the original source in a new tab)

FEBS Letters

Design
In vitro experiment measuring collagen synthesis in cultured fibroblasts exposed to GHK-Cu.
Population / setting
Fibroblast cultures; no people were treated. The abstract does not provide the number of experimental replicates.
Sample size
Not specified in this summary; consult the paper.

What was observed
GHK-Cu increased collagen synthesis in fibroblast cultures independently of a change in cell number. This supplies a mechanistic observation, not a measured clinical improvement in human skin.

Keep in view
Cell-culture findings cannot establish the benefit or safety of a serum, cream or injectable product. The abstract does not justify a universal percentage increase in collagen or a claim about wrinkles, wound healing or hair growth in people.

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Oral low-molecular-weight collagen peptides2018
Randomised trial

Oral Intake of Low-Molecular-Weight Collagen Peptide Improves Hydration, Elasticity, and Wrinkling in Human Skin: A Randomized, Double-Blind, Placebo-Controlled Study (opens the original source in a new tab)

Nutrients

Design
Randomised, double-blind, placebo-controlled trial of a defined oral fish-derived collagen formulation; 12 weeks.
Population / setting
Women aged 40–60 with visible crow’s-feet; 33 were allocated to the test formulation and 31 to placebo.
Sample size
n = 64

What was observed
Measured skin hydration was higher with the test formulation than placebo at weeks 6 and 12; the between-group comparison at week 12 had P=0.003. The paper also reported improvements in selected wrinkle and elasticity measures.

Keep in view
A small, short, product-specific cosmetic trial with multiple skin measurements does not establish anti-ageing benefits for all collagen products. Some authors were affiliated with collagen-related companies. Oral-formulation results do not support injectable peptide claims.

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Tesamorelin2007
Randomised trial

Metabolic Effects of a Growth Hormone–Releasing Factor in Patients with HIV (opens the original source in a new tab)

New England Journal of Medicine

Design
Randomised, double-blind, placebo-controlled trial of tesamorelin; 26 weeks.
Population / setting
Adults with HIV receiving antiretroviral therapy who had excess abdominal fat; 86% were men.
Sample size
n = 412

What was observed
Visceral adipose tissue decreased by 15.2% with tesamorelin and increased by 5.0% with placebo. The trial also reported lipid changes; it did not test whether cardiovascular events were reduced.

Keep in view
The population had HIV-associated abdominal fat accumulation, not uncomplicated obesity or a bodybuilding objective. A change in measured visceral fat is not proof of a reduction in clinical cardiovascular events, and the 26-week trial does not settle long-term safety.

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Bremelanotide (PT-141)2019
Randomised trial

Bremelanotide for the Treatment of Hypoactive Sexual Desire Disorder: Two Randomized Phase 3 Trials (opens the original source in a new tab)

Obstetrics & Gynecology

Design
Two similarly designed phase 3, double-blind, randomised, placebo-controlled trials; 24 weeks.
Population / setting
Premenopausal women with hypoactive sexual desire disorder. The two studies randomised 1,267 women; 1,202 formed the modified intention-to-treat efficacy population.
Sample size
n = 1,267

What was observed
The integrated placebo-adjusted changes were +0.35 points in the Female Sexual Function Index desire-domain score and −0.33 points in distress measured by FSDS-DAO item 13. Both coprimary endpoints favoured bremelanotide. Nausea, flushing and headache were more frequent.

Keep in view
The outcomes are changes on defined questionnaire scales, not a general percentage increase in libido or evidence for all sexual concerns. Participants were predominantly White and from US sites. The findings concern premenopausal women with the studied disorder. Industry-funded trials.

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Elamipretide (SS-31)2021
Randomised trial

A phase 2/3 randomized clinical trial followed by an open-label extension to evaluate the effectiveness of elamipretide in Barth syndrome, a genetic disorder of mitochondrial cardiolipin metabolism (opens the original source in a new tab)

Genetics in Medicine

Design
Randomised, double-blind, placebo-controlled crossover trial with 12-week treatment periods, followed by an open-label extension.
Population / setting
Participants with genetically confirmed Barth syndrome. Twelve entered the blinded trial; eight reached week 36 of the open-label extension.
Sample size
n = 12

What was observed
Neither blinded primary endpoint—six-minute walk distance or Barth Syndrome Symptom Assessment—was met. Among eight extension participants at week 36, mean walk distance improved by 95.9 m and the symptom score by −2.1 points relative to baseline.

Keep in view
The extension findings lack a concurrent placebo control and are vulnerable to selection and expectation effects. This very small rare-disease trial does not establish an anti-ageing, energy or athletic-performance benefit in healthy people. Published online in 2020 and in the 2021 journal issue.

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