Clinical-only: Metabolic / Weight Loss (Retatrutide + Cagrilintide)

Public • 2/6/2026

Investigational/clinical agents with strong RCT evidence in obesity-related indications (not supplements).

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Deterministic heuristics (stimulants, duplicates, hydration). Not medical advice.

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Stimulant estimate

0 mg

Only counts explicit caffeine items

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No obvious duplication/stimulant/hydration flags from the heuristic pass.

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Supplements

2 items

Retatrutide (LY-343794)High

PLACEHOLDER • Other • Click to expand

Human phase 2 RCT evidence for weight loss in obesity.

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1mg

Body weight reduction

High

Population: Adults with obesity (without diabetes) in a randomized controlled phase 2 trial

Study type: Randomized, double-blind, placebo-controlled phase 2 trial

Dose context: 12 mg typical (range: 1–12 mg) • Duration: 48 weeks

Retatrutide produced substantial mean body-weight reductions over 48 weeks (up to ~24% at highest dose), with larger losses at higher doses; GI adverse effects were common and dose-related.

Citation: Jastreboff et al., N Engl J Med (2023) — Triple–Hormone-Receptor Agonist Retatrutide for Obesity•DOI: 10.1056/NEJMoa2301972•https://www.nejm.org/doi/full/10.1056/NEJMoa2301972

Phase 3 registrational program design (TRIUMPH)

Low

Population: Adults with obesity ± OSA, knee osteoarthritis, or cardiovascular disease (>5800 participants across 4 trials)

Study type: Phase 3 registrational program design/rationale publication

Dose context: — • Duration: Ongoing (trials projected through 2025–2026)

The TRIUMPH phase 3 program (4 trials, >5800 participants) evaluates once-weekly subcutaneous retatrutide vs. placebo for weight management and obesity-related complications (OSA, OA, CVD). No primary efficacy results published as of early 2026; design and rationale published in 2025.

Citation: Wadden et al., Diabetes Obes Metab (2025) — Retatrutide for obesity, OSA and knee OA: Rationale and design of TRIUMPH•https://pubmed.ncbi.nlm.nih.gov/41090431/

CagrilintideHigh

PLACEHOLDER • Other • Click to expand

Clinical trial evidence in obesity programs (often combination development).

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1mg

Body weight reduction (phase 3 — REDEFINE 1, overweight/obesity without diabetes)

High

Population: Adults with overweight/obesity (without diabetes), n=3417 randomized

Study type: Randomized, double-blind, placebo-controlled and active-controlled phase 3a trial

Dose context: 2 mg typical (range: 0–2 mg) • Duration: 68 weeks

CagriSema (cagrilintide 2.4 mg + semaglutide 2.4 mg once weekly) produced an estimated mean body-weight reduction of -20.4% vs -3.0% with placebo at week 68 (P<0.001), superior to either component alone. GI adverse events were common (majority transient and mild-to-moderate). Published in NEJM 2025.

Citation: Lincoff et al., N Engl J Med (2025) — Coadministered Cagrilintide and Semaglutide in Adults with Overweight or Obesity (REDEFINE 1)•DOI: 10.1056/NEJMoa2501552•https://pubmed.ncbi.nlm.nih.gov/40544433/

Body weight and glycemic control (phase 3 — REDEFINE 2, type 2 diabetes)

High

Population: Adults with overweight/obesity and type 2 diabetes (n=1206 randomized)

Study type: Randomized, double-blind, placebo-controlled phase 3a trial

Dose context: 2 mg typical (range: 0–2 mg) • Duration: 68 weeks

CagriSema produced mean weight loss of -13.7% vs -3.4% with placebo at week 68, and 73.5% of patients achieved HbA1c ≤6.5% vs 15.9% with placebo. GI adverse events in 72.5% of CagriSema group (mostly transient/mild-moderate). Published in NEJM 2025.

Citation: Davies et al., N Engl J Med (2025) — Cagrilintide–Semaglutide in Adults with Overweight or Obesity and Type 2 Diabetes (REDEFINE 2)•DOI: 10.1056/NEJMoa2502082•https://pubmed.ncbi.nlm.nih.gov/40544432/

Weight loss and glycemic control — late-stage trial report (type 2 diabetes)

Low

Population: Adults with type 2 diabetes (CagriSema vs semaglutide)

Study type: Late-stage trial (news report; now superseded by peer-reviewed NEJM publication above)

Dose context: — • Duration: 68 weeks

Reuters news report (February 2026) described CagriSema outperforming semaglutide in a late-stage diabetes trial; this is now confirmed by the peer-reviewed REDEFINE 2 NEJM paper (see above).

Citation: Reuters (2026-02-02) — Novo Nordisk says CagriSema outperforms semaglutide in late-stage diabetes trial•https://www.reuters.com/business/healthcare-pharmaceuticals/novo-nordisk-says-cagrisema-outperforms-semaglutide-late-stage-trial-type-2-2026-02-02/

Discussion

Longevity & Metabolic Health Base

by@athlete

Foundational stack aimed at mitochondrial function, insulin sensitivity, and long-term healthspan.

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