Treatment and assessment
In part A, patients were randomized 1:1 to receive either subcutaneous once-daily cotadutide titrated 100–300 μg or matching placebo for 28 days (Extended Data Fig. Part A was double-blinded, with both investigators, patients and sponsor staff involved in the treatment or clinical evaluation of patients unaware of treatment allocation. An unblinded site monitor, who was not involved in treatment or clinical evaluation of patients, performed investigational product accountability. Part B was a part-blinded, randomized, active-comparator study, with investigators and patients unaware of allocation to either placebo or cotadutide; however, liraglutide was open-label. The cotadutide and placebo multidose pens were indistinguishable.Hepatic glycogen, HFF, blood glucose, gluconeogenesis and vitals were assessed at baseline and at the end of treatment. A safety follow-up visit took place 28 days after the administration of the last treatment.Participants underwent a 5-day washout of metformin and were admitted for 3 days before baseline and end of treatment assessment; participants were given identical, standardized meals during admission, without access to additional food or alcohol. Serial measurements of hepatic glycogen levels were performed using 