Antisense Inhibition of Glucagon Receptor by IONIS-GCGR Improves Type 2 Diabetes Without Increase in Hepatic Glycogen Content in Patients With Type 2 Diabetes on Stable Metformin Therapy.

Objective: To evaluate the safety and efficacy of IONIS-GCGR, a 2'--methoxyethyl antisense oligonucleotide targeting the glucagon receptor (GCGR), and the underlying mechanism of liver transaminase increases in patients with type 2 diabetes on stable metformin therapy.

Research Design And Methods: In three phase 2, randomized, double-blind studies, patients with type 2 diabetes on metformin received weekly subcutaneous injections of IONIS-GCGR (50-200 mg) or placebo for 13 or 26 weeks.

Results: Significant reductions in HbA were observed after IONIS-GCGR treatment versus placebo at week 14 (-2.