In PIONEER 8, patients with advanced disease (T2D mean duration of 15.0 years and taking insulin with or without metformin) had significant reductions in HbA1c levels with both the 7 mg dose and the 14 mg dose compared with the placebo at week 26 [ETD − 1.0%, 95% CI − 1.2 to − 0.8 (7 mg), − 1.4%, 95% CI − 1.6 to − 1.2 (14 mg); p  <  0.0001 for both]. This evidence concerns the gene INS and type 2 diabetes mellitus.