NAD+ vs Retatrutide
A detailed comparison to help you understand the differences and choose the right peptide for your research goals.
NAD+
Nicotinamide Adenine Dinucleotide (NAD+) is an essential coenzyme found in every living cell. It plays a central role in energy metabolism, DNA repair, gene expression, and cellular signaling. NAD+ levels naturally decline with age, and restoring them has become a major focus of longevity research. Injectable NAD+ bypasses the GI tract for higher bioavailability compared to oral precursors like NMN or NR.
Full details →Retatrutide
Retatrutide (LY3437943) is a first-in-class triple agonist peptide targeting GIP, GLP-1, and glucagon receptors simultaneously. Developed by Eli Lilly, it is currently in Phase 3 clinical trials and has demonstrated the highest weight loss of any obesity medication to date — up to 28.7% body weight reduction at 48 weeks. The triple-receptor mechanism represents the next evolution beyond dual agonists like tirzepatide.
Full details →Side-by-Side Comparison
| Aspect | NAD+ | Retatrutide |
|---|---|---|
| Mechanism | NAD+ is a critical substrate for sirtuins (SIRT1-7), a family of enzymes involved in DNA repair, inflammation regulation, and mitochondrial function. It also serves as a coenzyme for PARP enzymes (involved in DNA damage repair) and CD38 (involved in immune cell signaling). By directly replenishing cellular NAD+ pools, injectable NAD+ supports mitochondrial electron transport chain function, enhances ATP production, and activates longevity-associated pathways. | Retatrutide is a synthetic peptide that activates three incretin/metabolic hormone receptors: (1) GLP-1 receptor — appetite suppression, insulin secretion, delayed gastric emptying, (2) GIP receptor — enhanced insulin sensitivity, improved fat metabolism, (3) Glucagon receptor — increased energy expenditure, hepatic fat mobilization, thermogenesis. The glucagon receptor component is the key differentiator, adding an energy-expenditure mechanism absent from GLP-1 and dual GIP/GLP-1 agonists. The molecule uses a C20 fatty diacid for albumin binding, enabling once-weekly dosing. |
| Typical Dosage | Subcutaneous injection, typically 2–3 times per week. Start low and escalate: Twice per week protocol: Week 1: 20 mg (0.1 ml), Week 2: 40 mg (0.2 ml), Week 3+: 120 mg maintenance (0.6 ml). Three times per week protocol (e.g. Mon/Wed/Fri): Week 1: 20 mg (0.1 ml), Week 2: 40 mg (0.2 ml), Week 3+: 80 mg maintenance (0.4 ml). Volumes above assume 200 mg/ml concentration (100 mg vial reconstituted with 0.5 ml BAC water). Inject slowly — rapid administration increases flushing and nausea. Avoid back-to-back injection days. IV infusion (clinical setting): 250–750 mg per session over 2–4 hours. | Phase 2 trial doses: 0.5 mg, 4 mg, 8 mg, and 12 mg weekly. The 12 mg dose produced maximum weight loss (28.7%). Phase 3 trials are evaluating doses up to 12 mg. Dose escalation schedule similar to other GLP-1s (start low, increase every 4 weeks). Final approved dosing not yet established — Phase 3 trials ongoing. |
| Administration | Subcutaneous injection is the most practical route for self-administration. Inject slowly — rapid administration increases side effects (flushing, chest tightness, nausea). Some users split larger doses across multiple daily injections to improve tolerance. IV infusions provide the highest bioavailability but require a clinical setting. Store reconstituted NAD+ refrigerated and protect from light. NAD+ solutions are pH-sensitive; use bacteriostatic water for reconstitution. | Subcutaneous injection, once weekly. Phase 3 trials use pre-filled single-dose pens. Not yet commercially available — estimated FDA approval ~2027-2028. |
| Side Effects | Flushing and warmth (very common, especially at higher doses or fast injection rates). Nausea and mild GI discomfort. Chest tightness or pressure during injection (usually transient). Injection site pain or redness. Headache. These side effects are typically dose-dependent and diminish with slower administration and repeated use. | Phase 2 data: nausea (up to 25%), diarrhea (up to 22%), vomiting (up to 15%), constipation, decreased appetite. GI side effects were dose-dependent and generally mild-to-moderate. Lower rates of nausea compared to semaglutide, potentially due to GIP component. Increased heart rate observed at higher doses. |
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Key Differences
Unique to Retatrutide:
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