RESEARCH PEPTIDE FUNDAMENTALS / MATRIX
Four Compounds, Four Very Different Places on the Evidence Ladder
How a research chemical, a supplement-grade metabolite, and two approved drugs stack up on mechanism, evidence, and the single biggest caution for each.
The short version
This page lines up Ipamorelin, NAD+, Semaglutide, and Tesamorelin on the dimensions that matter most when trying to make sense of research-peptide claims: what category each falls into, its regulatory status, how deep the human evidence actually goes, and the single biggest thing to know before taking any of it seriously. The headline is simple: these four compounds are not comparable in any scientific sense — they act on completely different systems — but they are directly comparable on one axis that matters enormously to a newcomer: how far each one has actually traveled from lab idea to proven, approved use. Semaglutide and Tesamorelin have made that whole journey. NAD+ is a naturally occurring molecule sold as a supplement. Ipamorelin has not made the journey at all. None of this is medical advice, and no dose is recommended here.
The comparison matrix
| Dimension | Ipamorelin | NAD+ | Semaglutide | Tesamorelin |
|---|---|---|---|---|
| Category | Growth-hormone secretagogue (research peptide) | Redox coenzyme / cellular metabolite | GLP-1 receptor agonist (incretin peptide) | GHRH analogue (peptide hormone) |
| Regulatory status | Never approved anywhere; sold as a research chemical | Sold as a dietary supplement; also used as a compounded IV/injectable | FDA-approved (diabetes, weight management, cardiovascular risk, liver disease) | FDA-approved, but only for HIV-related lipodystrophy |
| Deepest human evidence | One inconclusive Phase 2 trial; one small PK study [3][4] | Multiple small-to-mid RCTs raising blood NAD+; outcome data still limited [7][8][10] | Multiple large multi-thousand-person outcome trials [13][14][15][16] | Multiple RCTs and a 2026 pooled analysis, but confined to one patient population [18][20][22] |
| Administration studied | Subcutaneous or IV injection | Oral capsule, or IV/injectable in clinical settings | Once-weekly subcutaneous injection, or daily oral tablet | Subcutaneous injection |
| Key caution | No long-term human safety data exists at all [3][4] | Efficacy for hard outcomes in humans remains unproven [6] | Digestive side effects are the leading reason people stop treatment [17] | Benefit disappears once treatment stops [22] |
Category and mechanism
The four compounds do not share a single mechanism — that is part of why they were chosen for a "fundamentals" guide rather than a themed one. Ipamorelin and Tesamorelin both work on the growth-hormone axis, but from different entry points: Ipamorelin triggers the ghrelin receptor, Tesamorelin triggers the GHRH receptor, and both ultimately push the pituitary to release the body's own growth hormone rather than supplying it directly. NAD+ is not a hormone signal at all — it is a metabolic building block every cell already uses to make energy and repair itself. Semaglutide works through an entirely separate hormone system, the incretin pathway, mimicking a gut signal that manages blood sugar and appetite.
Regulatory status
This is the dimension where the four compounds separate the most sharply. Semaglutide and Tesamorelin are both FDA-approved prescription medicines, which means they cleared full human trial programs demonstrating both benefit and an acceptable safety profile for their specific approved uses — though Tesamorelin's approval is narrow (one condition in one patient population) compared with Semaglutide's broader footprint across several. NAD+ is sold legally as a dietary supplement, and separately as a compounded IV or injectable product in some clinics, but neither route has gone through the drug-approval process. Ipamorelin has never been approved anywhere, for anything, and is sold explicitly as a research chemical not intended for human use.
How deep the human evidence goes
Semaglutide has by far the deepest evidence base of the four: multiple trials each involving thousands to tens of thousands of participants, tracking outcomes as serious as heart attacks and kidney failure, not just lab measurements [13][14][15][16]. Tesamorelin's evidence is also solid but narrower in scope — real randomized trials, but concentrated almost entirely in HIV-positive adults with a specific fat-redistribution condition [18][20][22]. NAD+ has a growing stack of small-to-mid-sized human trials showing it reliably raises blood NAD+ levels, but a 2025 review of that evidence found that translating those blood-level changes into proven improvements in outcomes people actually feel remains only partly demonstrated [6][7][10]. Ipamorelin sits at the far end: one human clinical trial, which did not meet its goal, plus a single small pharmacokinetics study — the thinnest human evidence base of the four [3][4].
The single biggest caution
Each compound has one caution worth remembering above the rest. For Ipamorelin, it is simply that no long-term human safety data exists at all — everything beyond a week or two of dosing is uncharted [3][4]. For NAD+, it is that raising a blood-test number is not the same as proving a real-world benefit, and the strongest current review says human efficacy data remain limited [6]. For Semaglutide, it is the well-documented pattern of digestive side effects, which is the single leading reason people discontinue treatment [17]. For Tesamorelin, it is that its benefit is not permanent — visceral fat measurably returns once treatment stops, meaning it functions as an ongoing therapy rather than a one-time fix [22].