Metabolism Peptides

A small molecule NNMT inhibitor studied for metabolic enhancement and fat cell reduction.

An oral, once-daily small-molecule amylin receptor agonist in first-in-human Phase 1 testing for obesity — an early entrant in the race to make amylin biology available as a pill rather than an injection.

An oral non-peptide small-molecule GLP-1 receptor agonist achieving 16.3% placebo-adjusted weight loss at 44 weeks in Phase 2 ACCESS II, with Phase 3 on track for Q3 2026 after positive FDA end-of-Phase 2 feedback.

A bifunctional GIPR-antagonist / GLP-1 receptor-agonist peptide in early clinical development for obesity, designed to improve the quality and durability of weight loss and long-term weight maintenance.

ALV-200 is Alveus Therapeutics' highly selective amylin receptor 3 (AMYR3) peptide agonist in IND-enabling development for obesity, designed to capture amylin's weight-loss and lean-mass-preserving benefits while avoiding the nausea and aversion tied to calcitonin-receptor activation. It is engineered for once-weekly dosing.

A unimolecular GLP-1 and amylin receptor dual agonist in Phase 3 trials, available in both subcutaneous and oral formulations, with up to 22% weight loss in Phase 1b/2a.

A modified fragment of human growth hormone studied for fat metabolism without growth-promoting effects.

Apitegromab (SRK-015) is an investigational, fully human IgG4 monoclonal antibody developed by Scholar Rock that inhibits myostatin - the muscle-produced growth factor that limits skeletal-muscle mass - through a novel, muscle-selective mechanism. Rather than neutralizing mature, active myostatin (the approach of earlier failed inhibitors), apitegromab binds only the inactive precursor forms of the protein - promyostatin and latent myostatin - stored locally in muscle, and blocks their proteolytic conversion into the active ligand. Because it spares the closely related growth factors activin A, BMP9/10, and TGF-beta1, it aims to avoid the off-target effects (such as bleeding and vascular changes) that sank broad ActRII-pathway drugs. Apitegromab is the first muscle-targeted therapy to succeed in a pivotal Phase 3 trial in spinal muscular atrophy (SMA): in the 156-patient SAPPHIRE study of nonambulatory Type 2/3 patients aged 2-12 already on an SMN-directed therapy (nusinersen or risdiplam), adding apitegromab (10 or 20 mg/kg IV every 4 weeks) improved motor function by a pooled 1.8 points on the Hammersmith Functional Motor Scale Expanded (HFMSE) versus placebo at 12 months (p=0.019). Scholar Rock's initial Biologics License Application received an FDA Complete Response Letter in September 2025 tied solely to a third-party (Catalent Indiana) fill-finish manufacturing inspection - not to the drug's efficacy or safety - and the company resubmitted the BLA on March 31, 2026, with a PDUFA target action date of September 30, 2026. In parallel, apitegromab produced positive Phase 2 obesity data (EMBRAZE): added to tirzepatide over 24 weeks it preserved about 55% more lean mass (roughly 1.9 kg / 4.2 lb) than tirzepatide alone, positioning myostatin inhibition as a potential lean-mass-sparing partner for GLP-1-based weight loss.

An oral once-daily small-molecule GLP-1 receptor agonist developed by Ascletis Pharma, showing 5.4–7.7% placebo-adjusted weight loss at 13 weeks in Phase 2, with in vitro potency 2–3x greater than orforglipron.

A next-generation once-monthly GLP-1R/GIPR dual agonist peptide with a 14-day half-life (6-fold longer than tirzepatide) and 71% greater weight loss than tirzepatide in preclinical models.

A next-generation once-monthly amylin receptor agonist peptide with a 32-day half-life and 91% greater weight loss than petrelintide in preclinical models. IND filing expected Q2 2026.

A next-generation once-monthly GLP-1R/GIPR/GCGR triple peptide agonist with 5-fold greater potency than retatrutide and a 17-day half-life enabling monthly dosing. IND filing expected Q2 2026.

ASC39 is Ascletis Pharma's investigational once-daily oral small-molecule amylin-selective amylin receptor agonist for obesity. In head-to-head preclinical assays it matched Eli Lilly's injectable peptide eloralintide on amylin-receptor potency, selectivity over the calcitonin receptor, and weight loss in diet-induced obese rats. Ascletis plans to file a U.S. FDA IND for ASC39 - and for a fixed-dose combination with its oral GLP-1 agonist ASC30 - in the third quarter of 2026.

A first-in-class adipose-targeted thyroid hormone receptor beta (THRβ) agonist designed for muscle-preserving weight loss. Phase 1 data at ECO 2026 showed 111.8% greater weight loss when combined with semaglutide vs semaglutide alone.

A first-in-class GIPR antagonist peptide in early clinical development for obesity, designed as a once-weekly combination partner that adds weight loss and improves insulin sensitivity independent of appetite suppression.

A first-in-class once-daily injectable GLP-1 receptor ANTAGONIST (exendin 9-39) from Amylyx for hyperinsulinemic hypoglycemia. The mirror image of GLP-1 agonists like semaglutide, it blocks GLP-1 to stop the insulin surges that cause post-bariatric hypoglycemia. Phase 3 LUCIDITY completed enrollment March 2026 with topline data expected Q3 2026.

A once-monthly injectable GLP-1 receptor agonist developed by Pfizer (acquired from Metsera), showing 12.3% placebo-adjusted weight loss in Phase 2b trials with a tolerability profile comparable to weekly semaglutide.

A potential first-in-class triple GLP-1, GIP, and NPY2 receptor agonist peptide entering Phase 2 development mid-2026 for obesity, developed by Boehringer Ingelheim using Gubra-discovered technology.

An anti-activin type II receptor antibody that promotes fat loss while preserving lean muscle mass, studied in combination with GLP-1 agonists for obesity.

A 12-amino-acid peptide discovered via AI that suppresses appetite by acting on the hypothalamus, without nausea or muscle loss observed in animal models.

A GIP/glucagon dual agonist that achieves weight loss comparable to retatrutide without GLP-1 receptor activity, potentially eliminating GI side effects. Published in Molecular Metabolism (April 2026).

A long-acting amylin analog studied for appetite regulation; NDA filed for CagriSema (cagrilintide + semaglutide) combination in December 2025, with FDA review expected in 2026.

A fixed-dose combination of cagrilintide (amylin analog) and semaglutide (GLP-1 agonist) studied for enhanced weight loss through dual hormonal pathways.

A newly discovered 12-amino acid anorexigenic peptide derived from the GDF15 prepropeptide region, representing a novel appetite-suppression pathway.

An oral, once-daily small-molecule GLP-1 receptor agonist (developmental code HDM1002) from Huadong Medicine, in clinical trials for obesity and type 2 diabetes — part of the next wave of GLP-1 'pills' competing with orforglipron.

A once-daily GLP-1/glucagon dual receptor agonist studied for MASH, obesity, and type 2 diabetes with demonstrated liver fat reduction and antifibrotic activity.

CX11 is an investigational once-daily oral small-molecule GLP-1 receptor agonist (Corxel/Vincentage) that produced up to 11.5% weight loss at 36 weeks in a 246-patient U.S. Phase 2 obesity trial, with a notably low 12-16% vomiting rate and no hepatic safety signal; global Phase 3 is planned after positive China Phase 3 results.

A novel once-weekly GLP-1/glucagon dual receptor agonist showing rapid weight loss in Phase 1 trials with preserved lean body mass and direct liver benefits.

An oral small-molecule GLP-1 receptor agonist discontinued by Pfizer in 2026 after a potential drug-induced liver injury signal, despite showing meaningful weight loss in Phase 2b.

A long-acting, once-weekly dual GLP-1 and GLP-2 receptor agonist peptide (Zealand Pharma) developed for obesity, uniquely pairing GLP-1-driven weight loss with GLP-2 activation intended to improve intestinal barrier function and reduce obesity-related low-grade inflammation; development was paused in November 2025.

A cAMP signaling-biased GLP-1 receptor agonist approved in China for chronic weight management, with Phase 3 data showing up to 15.4% weight loss.

Efimosfermin alfa (development code BOS-580) is an investigational, long-acting, engineered analog of the metabolic hormone fibroblast growth factor 21 (FGF21) being developed by GSK - which acquired the molecule from Boston Pharmaceuticals in May 2025 for $1.2 billion upfront and up to $800 million in milestones (potential ~$2 billion total) - for steatotic liver disease, principally metabolic dysfunction-associated steatohepatitis (MASH, formerly NASH). Its defining feature is a very long half-life engineered to allow once-monthly subcutaneous dosing - the least frequent schedule among the leading FGF21 analogs, contrasting with the once-weekly or every-two-weeks dosing of efruxifermin (an Fc-FGF21 fusion) and pegozafermin (a glycoPEGylated FGF21). Like the rest of the class, it activates FGF receptors (FGFR1c/2c/3c) together with the co-receptor beta-Klotho to cut liver fat, improve insulin sensitivity, lower triglycerides, and drive direct anti-inflammatory and anti-fibrotic effects in the liver. In a 24-week Phase 2 trial in biopsy-confirmed F2-F3 MASH, once-monthly efimosfermin achieved at least one-stage fibrosis improvement without worsening of MASH in about 45% of patients and MASH resolution without worsening of fibrosis in about 68%, both significantly better than placebo (published in The Lancet, 2025). It holds FDA Breakthrough Therapy designation and EMA PRIME (Priority Medicines) status for MASH, and has advanced into the Phase 3 ZENITH program (ZENITH-1 and ZENITH-2 in F2-F3 MASH), with a Phase 3 program in compensated (F4) MASH cirrhosis also underway; GSK has guided to a first potential launch around 2029.

Efinopegdutide (MK-6024, formerly HM12525A and JNJ-64565111) is an investigational once-weekly subcutaneous dual agonist of the GLP-1 and glucagon receptors being developed by Merck for metabolic dysfunction-associated steatohepatitis (MASH, formerly NASH) and steatotic liver disease. It is a synthetic oxyntomodulin-based peptide - a modified GLP-1/glucagon dual-agonist sequence conjugated to a human IgG4 Fc fragment through a 10 kDa polyethylene glycol linker using Hanmi Pharmaceutical's LAPSCovery half-life-extension platform, which stretches dosing to once weekly. The design pairs the GLP-1 arm (appetite suppression, glycemic control, weight loss) with a glucagon arm that raises energy expenditure and acts directly on the liver to burn hepatic fat - the feature that sets it apart from pure GLP-1 drugs. In the head-to-head Phase 2a trial in NAFLD (Journal of Hepatology, 2023), efinopegdutide 10 mg cut liver fat content by 72.7% at 24 weeks versus 42.3% for semaglutide 1 mg, with two-thirds of efinopegdutide recipients falling below the 5% liver-fat threshold that defines a normal liver. Merck holds FDA Fast Track designation for the MASH program and is running Phase 2b studies plus a dedicated trial in compensated cirrhosis due to steatohepatitis; the earlier type 2 diabetes and obesity indications were discontinued in favor of the liver focus.

Efocipegtrutide (Hanmi code HM15211) is an investigational, long-acting, once-weekly GLP-1/GIP/glucagon 'triple' receptor agonist being developed primarily for metabolic dysfunction-associated steatohepatitis (MASH, formerly NASH) rather than obesity alone. It is built on Hanmi's LAPSCovery platform as a chemical conjugate of a chimeric tri-agonist peptide (TA15211) fused to a human IgG4 Fc fragment, which extends its half-life via FcRn-mediated recycling and enables weekly subcutaneous dosing. By adding glucagon-receptor activation to the GLP-1/GIP dual mechanism, efocipegtrutide is designed to combine appetite suppression and glycemic control with increased energy expenditure and direct hepatic anti-steatotic, anti-inflammatory, and anti-fibrotic effects. In a Phase 1b/2a study in obese subjects with non-alcoholic fatty liver disease, 12 weeks of treatment reduced liver fat by roughly 20% to 59% (dose-dependent, MRI-PDFF) versus about 6% on placebo. It has FDA Fast Track designation for MASH and orphan-drug designations from the FDA and EMA for primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC), and idiopathic pulmonary fibrosis (IPF). The 52-week adaptive Phase 2 HM-TRIA-201 study (NCT04505436) in biopsy-confirmed MASH with fibrosis is the pivotal read the field is watching.

Efruxifermin (development codes EFX, AKR-001; originally AMG 876) is an investigational, once-weekly, subcutaneously injected analog of the metabolic hormone fibroblast growth factor 21 (FGF21) being developed by Akero Therapeutics for metabolic dysfunction-associated steatohepatitis (MASH, formerly NASH), including both pre-cirrhotic fibrosis and compensated (F4) cirrhosis. It is a bivalent Fc-FGF21 fusion protein - two engineered FGF21 sequences fused to a human immunoglobulin (IgG1) Fc domain - a design distinct from the glycoPEGylation used by its main FGF21-class rival, pegozafermin. The Fc fusion extends the very short half-life of native FGF21 to support once-weekly dosing while preserving agonism at FGF receptors (FGFR1c/2c/3c) together with the co-receptor beta-Klotho. In the 96-week Phase 2b HARMONY trial in biopsy-confirmed F2-F3 MASH, at least a one-stage improvement in fibrosis without worsening of MASH was reached by about 75% of patients on 50 mg and 46% on 28 mg versus 24% on placebo (published in The Lancet, August 2025). In the Phase 2b SYMMETRY trial in compensated MASH cirrhosis, about 39% of 50 mg patients with paired week-96 biopsies achieved reversal of cirrhosis without worsening of MASH versus 15% on placebo (published in the New England Journal of Medicine). Efruxifermin holds FDA Breakthrough Therapy designation and has advanced into the Phase 3 SYNCHRONY program (SYNCHRONY Histology in F2-F3 MASH, SYNCHRONY Outcomes in F4 compensated cirrhosis, and SYNCHRONY Real-World in non-invasively diagnosed MASH/MASLD, whose double-blind portion completed enrollment with safety results expected in 2026).

An investigational, once-daily oral small-molecule GLP-1 receptor agonist from AstraZeneca that delivered up to about 11.8% weight loss at 36 weeks in people with obesity or overweight and strong blood-sugar control in type 2 diabetes, and is now advancing into a large Phase 3 program. Unlike semaglutide and tirzepatide - which are injectable peptides - elecoglipron is a small chemical molecule that mimics the natural GLP-1 hormone at its receptor in the gut and hypothalamus, so it can be taken as a pill with no food or fasting restrictions and is easier and cheaper to manufacture at global scale than peptide drugs. In the Phase 2b VISTA trial (n=310) the 75 mg once-daily regimen produced an average body-weight reduction of 10.5% at 26 weeks (vs 0.6% placebo) that had not plateaued, reaching about 11.8% at 36 weeks, with up to 88.8% of participants achieving at least 5% weight loss. In the Phase 2b SOLSTICE trial in type 2 diabetes (n=404) the 75 mg regimen cut HbA1c by 1.9% at 26 weeks (vs 0.2% placebo) - with roughly 90% of participants reaching an HbA1c below 7% - alongside 7.7% weight loss, numerically ahead of an open-label oral semaglutide 14 mg comparator arm. Side effects were the familiar GLP-1 class gastrointestinal symptoms (nausea, constipation, diarrhea, vomiting), mostly mild to moderate, with infrequent discontinuations and no liver safety signals. Both trials were presented at the 2026 American Diabetes Association (ADA) Scientific Sessions in New Orleans and published simultaneously in The Lancet, and on June 8, 2026 AstraZeneca announced elecoglipron would move into an extensive Phase 3 program - the EMBOLD obesity trials and the ELUMINATE type 2 diabetes trials (including combination with dapagliflozin), plus cardiovascular and kidney outcome studies. Elecoglipron is an investigational prescription-stage medicine - it is not approved anywhere and is not a supplement or research chemical.

A selective, long-acting amylin receptor agonist in Phase 3 trials for obesity, offering a GLP-1-independent weight loss mechanism with up to 20.1% weight loss in Phase 2.

An investigational once-weekly, cAMP signal-biased dual GLP-1/GIP receptor agonist from Roche/Genentech that produced up to ~22.5% placebo-adjusted weight loss at 48 weeks in Phase 2 and is advancing to Phase 3 for obesity.

An oral PCSK9 inhibitor peptide that reduced LDL cholesterol by 57% in Phase 3 trials — matching injectable monoclonal antibodies in efficacy while offering once-daily pill convenience.

A new class of peptide-based weight loss therapeutics that act through the GFRAL/RET receptor in the brainstem, representing a non-GLP-1 mechanism for appetite suppression and energy expenditure regulation.

A novel triple agonist peptide targeting GLP-1 and peptide YY receptors Y1 and Y2, designed to suppress appetite and improve glycemic control while avoiding GI side effects common to first-generation GLP-1 drugs.

A first-in-class peptide-drug conjugate that simultaneously activates five metabolic receptors (GLP-1R, GIPR, PPARα, PPARγ, PPARδ), published in Nature in April 2026 with preclinical results surpassing tirzepatide and triple agonists.

An endogenous mitochondrial-derived peptide studied for neuroprotection, cellular stress resistance, and longevity, whose blood levels fall with age and are elevated in centenarians.

An oral once-daily small-molecule GLP-1 receptor agonist (Hengrui's HRS-7535, licensed to Kailera) that delivered up to 10.9% weight loss at Week 44 in a Chinese Phase 3 obesity trial and met its Phase 3 diabetes endpoint, now in a global Phase 2 dose-optimization study.

A lipotropic injection blend containing methionine, inositol, choline, and other compounds to support fat metabolism.

Amgen's once-monthly injectable GIP receptor antagonist and GLP-1 receptor agonist, showing up to 20% weight loss in phase 2 trials with a unique mechanism that blocks GIP while activating GLP-1.

A bispecific GIPR antagonist and GLP-1 receptor agonist antibody-peptide conjugate developed by Amgen for obesity and type 2 diabetes.

The first dual GCG/GLP-1 receptor agonist approved in China for obesity and T2D, with Phase 3 showing up to 20.1% weight loss at the 9 mg dose and superiority over semaglutide.

A GLP-1/GIP co-agonist prodrug engineered for once-monthly dosing using MBX Biosciences' PEP platform. Phase 1 blinded data showed 7% mean weight loss at 8 weeks with minimal GI side effects.

A novel quadruple agonist prodrug combining GLP-1, GIP, glucagon, and DACRA (dual amylin and calcitonin receptor agonist) activity in a single molecule, designed for once-monthly dosing and superior efficacy.

An ultra-long-acting GLP-1 receptor agonist designed for both once-weekly and once-monthly subcutaneous dosing, delivering double-digit weight loss with class-leading gastrointestinal tolerability in mid-stage trials.

MET-233i is a first-in-class, once-monthly ultra-long-acting amylin analog for obesity, originally developed by Metsera and now a Pfizer asset. In its Phase 1 trial it produced up to 8.4% placebo-subtracted weight loss after five weekly doses and showed a roughly 19-day half-life - the most durable of any reported amylin analog - supporting once-monthly subcutaneous dosing. It is engineered to be combined with Metsera's monthly GLP-1 agonist MET-097i in a single once-monthly injection.

A mitochondrial-derived peptide studied for metabolic regulation, exercise mimetic effects, and longevity.

The first oral quadruple receptor agonist targeting IGF-1, GLP-1, GIP, and glucagon receptors for obesity treatment with muscle preservation.

A coenzyme essential for cellular energy production, studied for anti-aging and metabolic support.

The first oral non-peptide GLP-1 receptor agonist, FDA-approved in April 2026 for chronic weight management with no food or water restrictions.

Palopegteriparatide (Yorvipath, developed as TransCon PTH) is Ascendis Pharma's once-daily prodrug of parathyroid hormone (1-34). An inert methoxy-PEG carrier is attached to PTH(1-34) through a TransCon linker that auto-cleaves at physiologic pH and temperature, releasing unmodified native-sequence PTH slowly enough to hold hormone levels inside the physiologic range for a full 24 hours. It is the first therapy approved as a true hormone replacement for chronic hypoparathyroidism rather than as an add-on to calcium and active vitamin D: in the Phase 3 PaTHway trial 78.7% of treated adults met a composite endpoint of normal serum calcium plus independence from conventional therapy at week 26, versus 4.8% on placebo. The FDA approved Yorvipath on August 9, 2024.

Pegozafermin (development code BIO89-100) is an investigational, long-acting analog of fibroblast growth factor 21 (FGF21) being developed for metabolic dysfunction-associated steatohepatitis (MASH, formerly NASH) and for severe hypertriglyceridemia (SHTG). Originally developed by 89bio and acquired by Roche in a deal announced in September 2025 (about $2.4 billion upfront and up to roughly $3.5 billion including a contingent value right), it uses site-specific glycoPEGylation to extend the very short half-life of native FGF21 to roughly 55-100 hours, enabling once-weekly or once-every-two-weeks subcutaneous dosing. FGF21 is a metabolic hormone that acts on liver, fat, and other tissues to improve insulin sensitivity, lower triglycerides, and exert direct anti-fibrotic and anti-inflammatory effects. In the Phase 2b ENLIVEN trial in biopsy-confirmed F2-F3 MASH, the 44 mg every-two-weeks dose produced at least a one-stage fibrosis improvement without worsening of MASH in about 27% of patients versus 7% on placebo, and MASH resolution without worsening of fibrosis in about 26% versus 2% on placebo, with benefits sustained through week 48. Pegozafermin holds FDA Breakthrough Therapy designation and EMA PRIME status for MASH and has advanced into the Phase 3 ENLIGHTEN program (ENLIGHTEN-Fibrosis in non-cirrhotic F2-F3 MASH and ENLIGHTEN-Cirrhosis in compensated F4 cirrhosis), plus the Phase 3 ENTRUST trial in SHTG.

A GLP-1/glucagon dual receptor agonist with FDA Breakthrough Therapy Designation for MASH, showing strong weight loss and liver benefits in Phase 2 trials.

An orally dosed synthetic intracellular peptide that acts on the endocannabinoid system; an early human trial showed reduced visceral fat and improved sleep without lean-mass loss.

A long-acting amylin analog in late-stage clinical development for chronic weight management, designed to deliver double-digit weight loss with a tolerability profile comparable to placebo.

An ultra-long-acting injectable GLP-1 receptor agonist enabling monthly dosing, with 12.3% placebo-adjusted weight loss in Phase 2b and 10 Phase 3 trials planned.

A next-generation mitochondria-targeting peptide that induces selective adipocyte apoptosis and mitochondrial uncoupling for weight loss without systemic toxicity.

An investigational triple agonist (GIP/GLP-1/glucagon) studied for obesity and metabolic disease.

A once-weekly injectable GLP-1/GIP dual receptor agonist in Phase 3 trials for obesity, with an oral formulation in development and backed by a record-setting $625M biotech IPO.

A GLP-1 receptor agonist FDA-approved for type 2 diabetes and chronic weight management.

A synthetic ERRα/β/γ pan-agonist studied as an 'exercise mimetic' for endurance, fat oxidation, and metabolic health.

A dual GLP-1/glucagon receptor agonist with FDA Breakthrough Therapy designation for MASH and Priority Review NDA filed February 2026. Phase 3 SYNCHRONIZE-1 reported 16.6% weight loss at 76 weeks; approval possible Q3 2026.

A GHRH analog FDA-approved for reducing visceral fat in HIV-associated lipodystrophy.

A dual GIP/GLP-1 receptor agonist FDA-approved for type 2 diabetes, weight management, and MASH with liver fibrosis.

A GLP-1/GIP/glucagon triple receptor agonist in Phase 2 development for type 2 diabetes and obesity, competing with retatrutide in the triple-agonist space.

An investigational oral and injectable GLP-1/GIP dual agonist showing 12.2% oral weight loss at 13 weeks at ECO 2026 and 14.7% injectable weight loss, with Phase 3 VANQUISH trials fully enrolled.

WVE-007 is Wave Life Sciences' investigational GalNAc-conjugated siRNA that silences the liver gene INHBE to lower the hepatokine Activin E, aiming to produce muscle-sparing fat loss. In the Phase 1 INLIGHT trial a single subcutaneous dose reduced visceral and total fat while preserving or increasing lean mass, with durable target knockdown that could support once- or twice-yearly dosing.

A unimolecular GLP-1 and amylin receptor co-agonist developed by Novo Nordisk, available in both subcutaneous and oral formulations, with Phase 2 data showing up to 24.3% weight loss and Phase 3 AMAZE trials initiated in 2026.

An investigational RNA-interference (RNAi) therapeutic from Arrowhead Pharmaceuticals designed to treat obesity by silencing a fat-storage gene in the liver. ARO-INHBE is a GalNAc-conjugated small interfering RNA (siRNA) that reduces hepatic expression of the INHBE gene and its secreted product, the hepatokine Activin E. INHBE is a genetically validated target: people who naturally carry rare loss-of-function variants in INHBE have a healthier (less abdominal) fat distribution and a lower risk of type 2 diabetes, suggesting that lowering Activin E with a drug could reproduce that protective metabolic profile. In an ongoing Phase 1/2a trial (AROINHBE-1001, NCT06700538), a single subcutaneous dose reduced serum Activin E by up to about 94%, and monotherapy reduced visceral fat by roughly 10-16% while modestly increasing lean tissue. Most strikingly, when added to the incretin drug tirzepatide in obese patients with type 2 diabetes, ARO-INHBE roughly doubled weight loss (-9.4% versus -4.8% at week 16) and roughly tripled reductions in visceral, total, and liver fat versus tirzepatide alone. These are small, early, interim results (as few as 3-4 participants per combination arm) - not proof of durable or long-term benefit. ARO-INHBE is investigational, is not approved anywhere, and is not a supplement or research chemical; it is studied only in clinical trials.

An investigational once-weekly injectable dual GLP-1/GIP receptor agonist - the same peptide class as tirzepatide (Zepbound/Mounjaro) - developed by China's Jiangsu Hengrui Pharmaceuticals as HRS9531 and licensed to U.S.-based Kailera Therapeutics, which is developing it globally (outside Greater China) as KAI-9531. In the pivotal 48-week Phase 3 GEMINI-1 trial in China (NCT06396429; 567 adults with obesity or overweight without diabetes), once-weekly HRS9531 produced mean weight loss of about 17.4-19.2% at the 4 mg and 6 mg doses (per-protocol/hypothetical estimand) versus roughly 1.4% for placebo, with about 44% of 6 mg patients losing at least 20% of body weight and broad improvements in blood pressure, lipids, insulin resistance, and inflammation (hsCRP). An earlier Phase 2 trial reported about 23.6% mean weight loss at the higher 8 mg dose by week 36 with no plateau. Hengrui has submitted a marketing application to China's NMPA for chronic weight management, and Kailera began a global Phase 3 program (KAI-9531) evaluating higher maintenance doses (8 mg and 10 mg) and longer treatment by late 2025. HRS9531/KAI-9531 is investigational, is not approved outside of any regulatory review in China, and is not a supplement or research chemical; it is studied only in clinical trials.