Tirzepatide

FDA-approved as Mounjaro for type 2 diabetes (May 2022), as Zepbound for chronic weight management (November 2023), and for MASH with moderate-to-advanced fibrosis (early 2026). 73.3% of patients taking 15 mg achieved MASH resolution at 52 weeks in SYNERGY-NASH. SUMMIT trial for HFpEF with obesity submission anticipated.

Effective: 2026

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

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

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 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.

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.

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

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

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

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.

A long-acting glucagon-like peptide-2 (GLP-2) analog given by once- or twice-weekly subcutaneous injection that helps the gut absorb more nutrients in short bowel syndrome, reducing dependence on IV (parenteral) nutrition.

A once-weekly basal insulin engineered as a single-chain insulin analog fused to an antibody (IgG2) Fc fragment, giving it a roughly 17-day half-life so a single subcutaneous injection covers a full week. Developed by Eli Lilly (code LY3209590, also called basal insulin Fc or BIF), efsitora is designed to replace daily long-acting insulin with a flat, ultra-stable weekly profile. In the large Phase 3 QWINT program it matched daily insulins glargine and degludec on A1C in type 2 diabetes, and in insulin-naive patients its simplified fixed-dose titration cut the number of dose adjustments dramatically while keeping hypoglycemia low. In type 1 diabetes (QWINT-5) it was non-inferior on A1C but showed a higher rate of severe hypoglycemia, a key safety caveat. As of mid-2026 efsitora is under FDA review for type 2 diabetes (a decision expected in the third quarter of 2026) and would compete directly with Novo Nordisk's once-weekly insulin icodec (Awiqli).

An investigational once-weekly subcutaneous dual GLP-1 and GIP receptor agonist from Roche/Genentech (acquired with Carmot Therapeutics for ~$2.7 billion; Roche code RO7795068). CT-388 is engineered as a 'signal-biased' agonist: it potently activates both incretin receptors but recruits little or no beta-arrestin, which is expected to reduce receptor internalization and desensitization and thereby prolong pharmacological activity. In a Phase 1b study it produced ~18.8% placebo-adjusted weight loss at 24 weeks, and in the Phase 2 CT388-103 dose-finding trial (469 adults with obesity/overweight) it delivered a placebo-adjusted mean weight loss of 22.5% at 48 weeks (efficacy estimand; 18.3% treatment-regimen estimand) at the top 24 mg dose, without reaching a plateau. Roche advanced CT-388 into Phase 3 in the first half of 2026, positioning it as a late-entrant competitor to tirzepatide (Zepbound) with a potentially differentiated biased-signaling mechanism.

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.

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.

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).

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.