ATR-258 / Atrogi - LARVOL DELTA

Muscle-sparing, anti-obesity and anti diabetic effects of ATR-258 in GAN diet induced mouse model of obesity, diabetes and MAFLD (EASD 2026) - "In a severe GAN diet-induced model of obesity, diabetes and MAFLD, ATR-258 preserved muscle while lowering fat mass and improving glycaemic control without reducing food intake. ATR-258 normalized glucose tolerance, lowered fasting glycaemia, enhanced insulin sensitivity and reduced liver weight, a key feature of MAFLD. These data support ATR-258 as a differentiated β 2 -AR modulator with potential to treat obesity- and diabetes-associated MAFLD while limiting sarcopenic weight loss."

Preclinical • Diabetes • Metabolic Disorders • Metabolic Dysfunction-Associated Steatotic Liver Disease • Obesity • Type 2 Diabetes Mellitus

ATR-258, a GRK2-biased beta-2 AR agonist, mitigates worsening of insulin resistance in type 2 diabetes after metformin withdrawal (EASD 2026) - P1 | "ATR-258 mitigated worsening of insulin resistance after metformin withdrawal in persons with T2D, as shown by divergent changes in insulin AUC, iAUC, and insulin:glucose ratio versus placebo. These findings support GRK2-biased β2AR modulators as a novel muscle-targeted approach to T2D warranting Phase 2 evaluation."

Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus • SLC2A4

ß2-Adrenergic Receptor Modulators Improve Insulin Sensitivity in Obese and PI3K-Mutant Mice (ADA 2026) - "Here, we evaluated the effects of the novel modulator ATR-258 on insulin sensitivity in DIO mice as well as effects of clenbuterol on Pik3r1^WT/Y657** mice heterozygous for a PIK3R1 mutation affecting the PI3K insulin signaling pathway, analogous to mutations causing SHORT syndrome with severe insulin resistance in humans. Male DIO mice (n = 9/group) received ATR-258 (0.3 or 1 mg/kg, oral gavage)... β2AR modulators improve insulin sensitivity in two mechanistically distinct murine models of insulin resistance and represent promising insulin sensitizing candidates for further development."

Late-breaking abstract • Preclinical • Metabolic Disorders • Obesity • PI3K • PIK3R1

ATR-258, a GRK2-Biased ß2AR Modulator, Mitigates Worsening of Insulin Resistance in Type 2 Diabetes after Metformin Withdrawal (ADA 2026) - P1 | "ATR-258 mitigated worsening of insulin resistance after metformin withdrawal in persons with T2D, as shown by divergent changes in insulin AUC, iAUC, and insulin:glucose ratio versus placebo. These findings support GRK2-biased β2AR modulation as a novel muscle-targeted approach to T2D warranting Phase 2 evaluation."

Late-breaking abstract • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus • SLC2A4

Atrogi announces first subjects dosed in human trial for lead candidate ATR-258 (PRNewswire) - "The 8-week, investigator-initiated, interventional study will examine biased β2-adrenergic receptor (β2-AR) signaling in human skeletal muscle, in overweight male volunteers, who will receive daily oral dosing of ATR-258, Atrogi's GRK-selective long-acting β2-agonist."

Trial status • Obesity

ATR: Biased GRK Signaling Via β2-Adrenergic Receptors in Human Skeletal Muscle (clinicaltrials.gov) - P2 | N=10 | Not yet recruiting | Sponsor: Morten Hostrup, PhD

New P2 trial • Genetic Disorders • Obesity

The Attractive 2 Trial - Pharmacokinetics of ATR-258 Oral Capsule vs. Oral Solution Formulations in Healthy Volunteers (clinicaltrials.gov) - P1 | N=21 | Completed | Sponsor: Atrogi AB | Recruiting ➔ Completed

Trial completion • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

ATR-258 Is a Precision Modulator of ß2-AR Signaling That Improves Glucose Homeostasis and Is Safe in Humans (ADA 2024) - "ATR-258 is a β2-AR agonist with a preferential signaling and safety profile resulting in beneficial effects on glucose homeostasis in preclinical models and a promising safety profile in humans. ATR-258 could lead the way of a new class of adrenergic agonists totreat T2D."

Late-breaking abstract • Diabetes • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus

The Attractive 2 Trial - Pharmacokinetics of ATR-258 Oral Capsule vs. Oral Solution Formulations in Healthy Volunteers (clinicaltrials.gov) - P1 | N=21 | Recruiting | Sponsor: Atrogi AB

New P1 trial • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

First-in-human Single and Multiple Dose Trial of ATR-258 (clinicaltrials.gov) - P1 | N=71 | Completed | Sponsor: Atrogi AB | Active, not recruiting ➔ Completed

Trial completion • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

The ATTRACTIVE 1 trial: a first-in-human, dose escalating, double-blind, placebo-controlled trial of ATR-258 in healthy and type 2 diabetes participants (EASD 2023) - P1 | "ATR-258 targets the β2-AR signaling pathway, leading to the stimulation of glucose uptake in skeletal muscle. Preliminary blinded safety data from HVs suggest that oral treatment with ATR-258 is safe and well tolerated at doses 0.25 - 2.5 mg, and ATR-258 has a favorable plasma half-life. PD measures in the T2D patients will be available at the time of the EASD meeting."

Clinical • P1 data • Diabetes • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus

First-in-human Single and Multiple Dose Trial of ATR-258 (clinicaltrials.gov) - P1 | N=76 | Active, not recruiting | Sponsor: Atrogi AB | Recruiting ➔ Active, not recruiting | Trial completion date: Jan 2023 ➔ Oct 2023 | Trial primary completion date: Jan 2023 ➔ Oct 2023

Enrollment closed • Trial completion date • Trial primary completion date • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

First-in-human Single and Multiple Dose Trial of ATR-258 (clinicaltrials.gov) - P1 | N=76 | Recruiting | Sponsor: Atrogi AB

New P1 trial • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus