Pipeline Radar

Mechanism

First triple hormone receptor agonist targeting GLP-1, GIP, and glucagon receptors. The glucagon component increases thermogenesis through brown adipose tissue and hepatic fat oxidation — providing a metabolic lever beyond appetite suppression alone.

Key Data

TRIUMPH-4 (n=445; knee osteoarthritis; 68 weeks): 28.7% weight loss at 12 mg, with 75.8% reduction in knee pain score. Phase 2: up to 24.2% weight loss at 48 weeks. Phase 3 diabetes trial (March 2026): met primary A1C endpoint with 15% weight loss.

Mechanism

First oral non-peptide small-molecule GLP-1 RA — unlike Rybelsus (which requires a special absorption enhancer), orforglipron is inherently oral-friendly through conventional pharmacokinetics. No food or water timing restrictions.

Key Data

ATTAIN-1 (obesity; 72 weeks): 12.4% weight loss; 59.6% achieved ≥10%. ATTAIN-2 (T2D; 72 weeks): 10.5% weight loss + 1.8% A1C reduction. ACHIEVE-3 (head-to-head vs. oral semaglutide; published Lancet February 2026): orforglipron superior on both A1C and weight. ATTAIN-MAINTAIN: superior to placebo for weight maintenance after switching from Wegovy/Zepbound.

Mechanism

Fixed-dose combination of cagrilintide (long-acting amylin agonist) + semaglutide. Amylin is co-secreted with insulin and regulates postprandial glucose, delays gastric emptying, and promotes satiety through distinct hypothalamic receptors.

Key Data

REDEFINE 1 (n=3,417; obesity; 68 weeks): 20.4% weight loss; 60% achieved ≥20%; 23% achieved ≥30%; 88% of prediabetics reverted to normoglycemia. REDEFINE 2 (n=1,206; T2D; 68 weeks): 13.7% weight loss; 73.5% reached A1C ≤6.5%.

Mechanism

Dual agonist of GLP-1 and glucagon receptors. Unlike tirzepatide (GLP-1/GIP), the glucagon component increases thermogenesis through brown adipose tissue activation and hepatic fat oxidation — potentially producing weight loss through increased energy expenditure rather than appetite suppression alone.

Key Data

Phase 2 (46 weeks): up to ~19% weight loss. SYNCHRONIZE-1 and -2 (Phase 3; 76 weeks): results pending Q2 2026. SYNCHRONIZE-CVOT: 5,508 patients — one of the largest CVOTs in the obesity drug class.

Mechanism

First-in-class single molecule activating both GLP-1 and amylin receptors. Unlike CagriSema (two separate molecules), amycretin provides fixed 1:1 stoichiometry. Developed for both subcutaneous and oral administration.

Key Data (Phase 2; T2D; 36 weeks)

Subcutaneous: up to 14.5% weight loss. Oral (once-daily): up to 10.1% weight loss; HbA1c ≤7.0% in 77.6%.

Mechanism

Monoclonal antibody inhibiting activin Type II receptors (ActRII), blocking myostatin and activin signaling. This increases muscle protein synthesis and reduces fat accumulation — a direct tissue-level anabolic mechanism independent of appetite suppression.

Key Data (BELIEVE Trial; Nature Medicine 2026)

Bimagrumab + semaglutide: 22.1% total weight loss; 92.8% of weight lost was fat (vs. 71.8% with semaglutide alone). Lean mass reduction: only −2.6% (combo) vs. −7.9% (semaglutide alone). Bimagrumab monotherapy: increased lean mass by +2.5%. Up to 83% decrease in hsCRP (inflammation marker).

Mechanism

Peptide-based dual GLP-1/glucagon receptor agonist. Glucagon receptor activation increases resting energy expenditure through thermogenesis, theoretically sparing lean mass by maintaining metabolic rate during caloric deficit.

Key Data (MOMENTUM Phase 2; 48 weeks)

2.4 mg dose: 15.6% weight loss. Lean mass as % of total weight lost: only 21.9% — the lowest reported in any incretin therapy trial. Fat comprised 78.1% of total weight lost.

Mechanism

Fully human monoclonal anti-GIPR antagonist antibody conjugated to two GLP-1 agonist peptides. GLP-1 suppresses appetite; GIPR antagonism blocks GIP's counter-regulatory effects. The antibody scaffold enables once-monthly or longer dosing due to extended half-life. Notably, this is the opposite GIPR approach from tirzepatide (agonist vs. antagonist).

Key Data (Phase 2; 52 weeks)

Obesity without T2D: up to ~20% weight loss. Obesity with T2D: up to 17%. Dosing: monthly or potentially longer intervals. Amgen has launched an expansive Phase 3 program spanning chronic weight management, CVOT, heart failure, and OSA.