Figure 1. Mean change in BW (kg) from baseline to end of treatment ± SE in the SUSTAIN 1–3 trials. *P < 0.0001 vs ... Figure 1. Mean change in BW (kg)

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Figure 1. Mean change in BW (kg) from baseline to end of treatment ± SE in the SUSTAIN 1–3 trials. *P < 0.0001 vs ... Figure 1. Mean change in BW (kg) from baseline to end of treatment ± SE in the SUSTAIN 1–3 trials. *P < 0.0001 vs comparator. Based on “on-treatment without rescue medication” data from subjects in the full analysis set. Mean change in BW was estimated using a mixed model for repeated measurements that included treatment, country, and baseline BW as variables, all nested within visit. n: number of subjects with valid observation at landmark visit; N: full analysis set. MET, metformin; TZD, thiazolidinedione. Unless provided in the caption above, the following copyright applies to the content of this slide: Copyright © 2019 Endocrine Society None, Volume 104, Issue 9, 02 April 2019, Pages 4078–4086, https://doi.org/10.1210/jc.2018-02685 The content of this slide may be subject to copyright: please see the slide notes for details.

Figure 2. Change in IR from baseline to end of treatment in (a) SUSTAIN 1, (b) SUSTAIN 2, and (c) SUSTAIN 3 by ... Figure 2. Change in IR from baseline to end of treatment in (a) SUSTAIN 1, (b) SUSTAIN 2, and (c) SUSTAIN 3 by weight-change category. Based on “on-treatment without rescue medication” data from subjects in the full analysis set, with missing data imputed from a mixed model for repeated measurements. Weight-change categories were chosen to ensure sufficient subject numbers in each group. Relative change from baseline in HOMA-IR (%) was calculated from the geometric mean ratio to baseline. Values were analyzed on a logarithmic scale and back-transformed into the original scale. Dashed lines represent change in WL category. n: subjects contributing to summary; N: full analysis set. MET, metformin; TZD, thiazolidinedione. Unless provided in the caption above, the following copyright applies to the content of this slide: Copyright © 2019 Endocrine Society None, Volume 104, Issue 9, 02 April 2019, Pages 4078–4086, https://doi.org/10.1210/jc.2018-02685 The content of this slide may be subject to copyright: please see the slide notes for details.

Figure 3. Relationship between BW and IR in (a) SUSTAIN 1, (b) SUSTAIN 2, and (c) SUSTAIN 3. “On-treatment without ... Figure 3. Relationship between BW and IR in (a) SUSTAIN 1, (b) SUSTAIN 2, and (c) SUSTAIN 3. “On-treatment without rescue medication” data are shown, with missing data imputed from a mixed model for repeated measurements. Dotted lines show regression lines fitted for each treatment separately on log-transformed IR values. Regression equations for SUSTAIN 1: semaglutide 0.5 mg y = 0.8498e<sup>0.0352x</sup>, semaglutide 1.0 mg y = 0.7790e<sup>0.0324x</sup>, placebo y = 0.8846e<sup>0.0431x</sup>; for SUSTAIN 2: semaglutide 0.5 mg y = 0.7912e<sup>0.0467x</sup>, semaglutide 1.0 mg y = 0.7385e<sup>0.0486x</sup>, sitagliptin y = 0.7251e<sup>0.0141x</sup>; for SUSTAIN 3: semaglutide 1.0 mg y = 0.7114e<sup>0.043x</sup>, exenatide ER y = 0.7704e<sup>0.0334x</sup>. The y-axes scales are logarithmic. Unless provided in the caption above, the following copyright applies to the content of this slide: Copyright © 2019 Endocrine Society None, Volume 104, Issue 9, 02 April 2019, Pages 4078–4086, https://doi.org/10.1210/jc.2018-02685 The content of this slide may be subject to copyright: please see the slide notes for details.

Figure 4. Improvement in insulin resistance at end of treatment mediated, or not mediated, by weight change. Based on ... Figure 4. Improvement in insulin resistance at end of treatment mediated, or not mediated, by weight change. Based on “on-treatment without rescue medication” data from subjects in the full analysis set, with missing data imputed from a mixed model for repeated measurements. The effects were estimated using an imputation-based mediation analysis (18). Mean estimates and 95% CIs are calculated on log-scale and back-transformed to original scale. N/A, not applicable. Unless provided in the caption above, the following copyright applies to the content of this slide: Copyright © 2019 Endocrine Society None, Volume 104, Issue 9, 02 April 2019, Pages 4078–4086, https://doi.org/10.1210/jc.2018-02685 The content of this slide may be subject to copyright: please see the slide notes for details.