These are the atomic notes the GLP Dex agent carries as context. Each note is a compressed, self-contained unit of knowledge — enough to reason from, with a link to the full source when depth is needed. This is the manual knowledge layer, not a live retrieval system.
Series context
GLP Dex is a drug reference series covering every major GLP-1 receptor agonist in development or approved as of mid-2026. Organized into five families by mechanism: Single Agonists → Dual Agonists → Triple Agonists → Oral GLP-1 → Emerging Modalities. Foundation in The Receptor Game.
Three receptors matter: GLP-1R (appetite + insulin), GIPR (amplifies GLP-1 satiety signal), GCGR (energy expenditure + liver fat). Every drug in this series targets some combination of these.
Efficacy ceiling by family: Single ~15% → Dual GIP ~21% → Dual glucagon ~19% → Triple ~24% → Oral ~16% → Emerging ~23%.
Single Agonists — GLP-1R only
Semaglutide
Approved. Ozempic (T2D injection), Wegovy (obesity injection), Rybelsus (T2D oral). 14.9% weight loss STEP 1 at 68w. 20% MACE reduction SELECT trial — cardiovascular indication. Class benchmark. SURMOUNT-5: tirzepatide produced 47% more relative weight loss. → full profile
Liraglutide
Approved. Saxenda (obesity), Victoza (T2D). Once-daily injection — higher daily friction than weekly drugs. ~8% weight loss SCALE at 56w. First in class to show cardiovascular benefit (LEADER). Declining market share as weekly drugs dominate. → full profile
Exenatide
Approved. Byetta (twice-daily), Bydureon BCise (weekly ER). First GLP-1 drug approved anywhere (2005), derived from Gila monster peptide. ~2–3kg weight loss, T2D only, no obesity indication. Mainly cost-sensitive or legacy prescribing. → full profile
Dulaglutide
Approved. Trulicity, once-weekly Fc-fusion. ~3kg weight loss AWARD trials. Broader CV label than semaglutide (REWIND includes lower-risk patients). Hidden-needle autoinjector — strong with injection-averse patients. Superseded on weight loss by tirzepatide. → full profile
Ecluglutide
Approved China 2025, Pfizer global partnership. First cAMP-biased GLP-1R agonist — designed to reduce β-arrestin-mediated GI side effects at equivalent efficacy. ~15.4% weight loss Phase 3 China. Not yet available US/EU. Key for: prior GLP-1 intolerance. → full profile
Dual Agonists — GLP-1/GIP branch
Tirzepatide
Approved. Mounjaro (T2D), Zepbound (obesity), sleep apnea indication 2024. 20.9% weight loss SURMOUNT-1 at 72w. 47% more than semaglutide head-to-head. Current approved efficacy standard. Weekly injection. → full profile
VK2735
Phase 3. Sub-Q and oral formulations in development separately. 14.7% at 13w sub-Q (VENTURE), 8.2% at 13w oral (ACHIEVE-1). First dual agonist with an oral candidate in Phase 3. Key for: injection-averse + wanting dual agonist efficacy. → full profile
Olatorepatide
Phase 3. Hansoh Pharma / Regeneron. 19.3% weight loss at 48w Phase 3 Chinese cohort (OASIS-1). China-to-global pipeline model. Not yet US/EU available. → full profile
Dual Agonists — GLP-1/glucagon branch
Glucagon agonism adds: resting energy expenditure + direct hepatic fat oxidation. Key for MASH patients. Different from GLP-1/GIP — glucagon raises blood glucose so titration is slower.
Survodutide
Phase 3. Boehringer Ingelheim / Zealand. ~19% weight loss Phase 2 at 46w. ~67% MASH resolution Phase 2 — highest pharmacological number for liver disease. Dual indication path: obesity + MASH. → full profile
Pemvidutide
Phase 2 complete, Phase 3 pending. Altimmune. ~15.6% weight loss MOMENTUM at 48w. MASH primary registration strategy. → full profile
Mazdutide
Approved China 2025. Innovent / Lilly. ~14.5% at 24w GLORY trials (short duration — efficacy continues past 24w). First GLP-1/glucagon approval globally. Not yet US/EU. → full profile
Triple Agonists — GLP-1R + GIPR + GCGR
Retatrutide
Phase 3 (TRIUMPH). Eli Lilly. 24.2% weight loss at 24w Phase 2 — highest ever recorded for a non-surgical obesity intervention. All three receptor mechanisms simultaneously. FDA filing ~2027. Key for: patients who want maximum available efficacy, or who've plateaued on tirzepatide. → full profile
Oral GLP-1 — non-peptide small molecule
No food restrictions, no injection, manufactured through conventional chemistry (lower cost of goods than peptide biologics).
Orforglipron
Phase 3. Eli Lilly. 14.7% weight loss at 36w Phase 2. No fasting requirement (unlike Rybelsus). Once-daily pill. Results expected mid-2026. Key for: injection-averse, cost sensitivity long-term, T2D. → full profile
Aleniglipron
Phase 2 complete, Phase 3 H2 2026. Structure Therapeutics. 16.3% at 26w GLIMMER. Lower GI discontinuation rates than orforglipron in Phase 2. Key for: prior GLP-1 intolerance + preference for oral. → full profile
Emerging Modalities
CagriSema
Phase 3. Novo Nordisk. Semaglutide + cagrilintide (amylin) co-formulated weekly injection. ~22.7% weight loss REDEFINE 1 at 68w. Two satiety circuits: GLP-1 (hypothalamus) + amylin (brainstem). Advantage appears at longer duration — Phase 2 at 32w looked like semaglutide alone. → full profile
MariTide
Phase 3. Amgen. Monthly injection. GLP-1R agonist + GIPR antagonist (opposite of tirzepatide). ~17.3% at 52w Phase 2, non-plateauing curve. Key for: weekly injection fatigue, patients wanting mechanistic alternative to tirzepatide. → full profile
ASC30
Phase 2 complete. Ascletis. Monthly → quarterly dosing target. Same GLP-1R mechanism as semaglutide, ultra-long half-life engineering. Key for: maximum dosing interval, long-term maintenance adherence. → full profile
Petrelintide
Phase 2. Zealand / Roche. Amylin receptor only — no GLP-1R involvement. ~10.7% weight loss Phase 2. The only pharmacological weight loss option for GLP-1-intolerant patients. Also a combination partner for patients who can tolerate both. → full profile
Intake logic
Five questions, asked one at a time, in conversation:
- T2D? — Yes changes which drugs are indicated and covered
- Insurance or cash pay? — Insurance = step therapy likely (semaglutide first). Cash = go direct to best clinical fit
- Prior GLP-1 history? — Never tried / stopped (no results) / stopped (side effects) — three different starting points
- Delivery preference? — Weekly injection / daily pill / monthly injection
- Primary goal? — Weight loss / blood sugar / liver disease / cardiovascular risk
Reasoning keys
- Contraindications first: pancreatitis history, thyroid cancer history → flag before recommending
- Pipeline drugs: flag as not yet available, give nearest current alternative
- Insurance + no prior GLP-1: start with semaglutide, explain step therapy
- Cash pay + no prior GLP-1 + max efficacy goal: tirzepatide
- Prior GLP-1 stopped due to nausea: ecluglutide (not yet US), aleniglipron (Phase 3), or tirzepatide (different GI profile for some)
- MASH primary: survodutide or pemvidutide (GLP-1/glucagon branch)
- Injection-averse: orforglipron or aleniglipron (oral), VK2735 oral (Phase 3), or MariTide monthly
- Maximum efficacy, willing to wait: retatrutide Phase 3, ~2027
- Narrow to two candidates max before recommending one