Figure 3.

Relationship of the two coprimary outcomes: hyperglycemic clamp-derived β-cell responses (steady-state C-peptide and ACPR_max) paired with M/I. Changes are shown from baseline to 12 and 15 months for the clamp-derived β-cell responses of steady-state C-peptide (A) and ACPR_max (B) paired with M/I. The black line depicts the joint relationship between β-cell response and M/I at baseline for the full cohort, with the mean value at baseline for the full cohort indicated by the black box with a 0. The dotted lines to boxes at months 12 and 15 show the trajectory of values from baseline to 12 months of intervention and then to 3 months after discontinuation of the intervention (15 months) for glargine followed by metformin (green) and metformin alone (brown). Values above the black line represent improved β-cell function, and values below the line represent poorer β-cell function. The ellipses depict the 95% confidence bands around the points at months 12 and 15. No significant differences were observed at any time point between treatment arms; however, significant within-group declines were seen from baseline while on active treatment through 12 months for steady-state C-peptide with M/I (glargine followed by metformin P = 0.019, metformin alone P = 0.025) and ACPR_max with M/I (glargine followed by metformin P < 0.001, metformin alone P = 0.001) and through 15 months for steady-state C-peptide with M/I (glargine followed by metformin P < 0.001, metformin alone P = 0.031) and ACPR_max with M/I (glargine followed by metformin P = 0.001, metformin alone P < 0.001).