What does this study add?

• The results revealed that LY3437943 is similar in the overall safety profile vs the incretin class in general. There were no clinically significant alterations or trends in safety laboratory values, no hypoglycemic events or injection site related treatment emergent adverse events (TEAEs), and no deaths in any LY3437943-treated groups.
• There was an increase in TEAEs when patients were escalated from 3 mg to 6 mg and 9 mg and 12 mg, due to gastrointestinal (GI) tolerability.
• The LY3437943 doses were well-tolerated up to the 9 mg and 12 mg doses, at which points GI intolerability was observed as nausea, vomiting, and diarrhoea (although most GI TEAEs did not require treatment and resolved within ~10 days).
• Vital sign results showed that mean systolic and diastolic blood pressure decreased from baseline in LY3437943-treated groups whilst pulse rate increased; this is similar to results from other incretins in Phase 1 studies with limited optimization of titration steps.³
• The PK profile studies attained a T_max 12–48 hours post-dose, the half-life was ~6 days (therefore supporting once-weekly dosing), and the AUC_(0-tau) and C_max were proportional across the dose range studied.¹
• LY3437943 treatment ≥3 mg resulted in significantly decreased mean haemoglobin A1c (HbA1c) level – the key efficacy parameter in the T2D population.
• LY3437943 treatment ≥3 mg dose-dependently decreased mean body weight – for example, in the 12 mg treatment group the average body weight decreased by 9 kg and in the 3 mg treatment group the average body weight decreased by 4 kg.