# Which claims earn confidence?

> Claims worth backing | Bullish Peptides — Bullish Peptides compares the strongest supported claims for semaglutide, tirzepatide, tesamorelin and MOTS-c, with the limits beside each.

The most optimistic conclusion changes with the question. Cardiovascular events, weight, fat location and mouse biology each have their own record.

## A comparison of the strongest claims

I can be bullish about a finding without giving the whole molecule a favourable verdict. The following entries say what earns confidence and which extension would need more work. They are questions for the literature, rather than a treatment ranking.

| Compound | Claim supported here | Question left open |
| --- | --- | --- |
| [Semaglutide](/semaglutide) | [Fewer combined cardiovascular events in SELECT](https://pubmed.ncbi.nlm.nih.gov/37952131/), in adults with established cardiovascular disease and excess weight, without diabetes | How broadly does that benefit extend beyond the people enrolled? |
| [Tirzepatide](/tirzepatide) | [Greater mean weight loss than semaglutide in SURMOUNT-5](https://pubmed.ncbi.nlm.nih.gov/40353578/), in adults with obesity without type 2 diabetes | How do other health outcomes and tolerability compare? |
| [Tesamorelin](/tesamorelin) | [Reduced visceral and liver fat](https://pubmed.ncbi.nlm.nih.gov/25038357/) in adults with HIV-associated abdominal fat accumulation | What persists after treatment ends, and how does the evidence translate beyond HIV? |
| [MOTS-c](/mots-c) | [Improved glucose handling and protection from diet-induced obesity in mice](https://pubmed.ncbi.nlm.nih.gov/25738459/) | Does giving MOTS-c to people produce a useful, acceptably safe effect? |

## Weight comparisons

SURMOUNT-5 makes the direct comparison: -20.2% mean body-weight change with tirzepatide and -13.7% with semaglutide at 72 weeks in 751 adults with obesity without type 2 diabetes. The [same trial compared both treatments](https://pubmed.ncbi.nlm.nih.gov/40353578/). STEP 1’s semaglutide result and SURMOUNT-1’s tirzepatide results came from separate trials; stacking those percentages would introduce differences in participants and design.

For weight, the experiment that compared the treatments directly gets my backing. Neither a larger weight reduction nor the word “peptide” answers every cardiovascular, kidney or muscle-function question.

## Duration and fat location

Tesamorelin’s [52-week findings](https://pubmed.ncbi.nlm.nih.gov/18690162/) include both sustained visceral-fat reduction during treatment and reaccumulation after stopping. That makes the time after treatment a central part of its case. Its scan-area measurements also concern a different outcome from total body weight.

A [pooled increase in lean body mass with tesamorelin](https://pubmed.ncbi.nlm.nih.gov/41545261/) cannot be read as stronger muscles: water and organs count towards that measure. With large weight loss, lean-tissue loss raises a different concern. Function deserves to be measured directly.

## Tolerability

[Semaglutide’s safety review](https://pubmed.ncbi.nlm.nih.gov/34305810/) describes common gastrointestinal effects and increased biliary disease. The [tirzepatide meta-analysis](https://pubmed.ncbi.nlm.nih.gov/37908750/) found increased combined gallbladder or biliary disease while leaving an increased pancreatitis risk unconfirmed. These are meaningful limits alongside meaningful benefits.

MOTS-c has a more basic gap: these papers establish no human treatment safety. Tesamorelin’s approved HIV-associated use comes with growth-hormone and IGF-1 concerns. An optimistic comparison needs space for known harms and missing measurements alike. My judgement would change with stronger human outcomes, longer follow-up and clearer evidence about physical function.

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Bullish Peptides is an independent cohort-first literature digest—not a clinic, a peptide counter, or a permission slip to outrun the evidence.