Improved treatment satisfaction in patients with type 2 diabetes treated with once-weekly semaglutide in the SUSTAIN trials

Abstract

Aim: To investigate treatment satisfaction with semaglutide, a once-weekly glucagon-like peptide-1 receptor agonist, versus placebo/active comparators in the SUSTAIN clinical trial programme.

Methods: In SUSTAIN 2-5 and 7, the Diabetes Treatment Satisfaction Questionnaire was used to evaluate patient-perceived treatment satisfaction, hyperglycaemia and hypoglycaemia. Post hoc subgroup analyses were conducted to explore the effects of gastrointestinal adverse events (GI AEs), weight loss (≥5%) or achieving glycaemic (HbA1c < 7%) targets on treatment satisfaction.

Results: Overall treatment satisfaction increased from baseline to end of treatment with all treatments across trials. Improvements were significantly greater with semaglutide versus comparators/placebo in SUSTAIN 2-5 (all P < 0.05), and generally greater in patients who achieved versus did not achieve weight loss and glycaemic targets, often with greater improvements with semaglutide 1.0 mg versus comparator/placebo in both weight loss groups. In SUSTAIN 7, improvements in overall treatment satisfaction were generally similar between semaglutide and dulaglutide, irrespective of weight loss or glycaemic control. In SUSTAIN 7, changes in overall treatment satisfaction score were generally lower in patients with versus without GI AEs at week 16 (except dulaglutide 0.75 mg), but similar by week 40. Perceived hyperglycaemia was significantly reduced from baseline to end of treatment with semaglutide versus all comparators/placebo (all P < 0.05). No differences between treatments were observed for perceived hypoglycaemia.

Conclusions: Semaglutide was associated with significantly greater (SUSTAIN 2-5) or similar (SUSTAIN 7) improvements in overall treatment satisfaction versus comparators/placebo. Improvements in overall treatment satisfaction were generally greater in patients achieving versus not achieving treatment targets. Clinicaltrials.gov: NCT01930188 (SUSTAIN 2), NCT01885208 (SUSTAIN 3), NCT02128932 (SUSTAIN 4), NCT02305381 (SUSTAIN 5) and NCT02648204 (SUSTAIN 7). EudraCT: 2012-004827-19 (SUSTAIN 2), 2012-004826-92 (SUSTAIN 3), 2013-004392-12 (SUSTAIN 4), 2013-004502-26 (SUSTAIN 5) and 2014-005375-91 (SUSTAIN 7).

Keywords: glucagon-like peptide-1 analogue; hypoglycaemia; incretin therapy; type 2 diabetes; weight control.

Conflict of interest statement

J.J. reports consultant fees from AstraZeneca, Boehringer Ingelheim, Eli Lilly, Novo Nordisk, Medtronic and Sanofi; serving on speaker bureau for Boehringer Ingelheim, Eli Lilly, Novo Nordisk and Merck; all outside the submitted work. A.L.B. reports personal fees from Novo Nordisk during the conduct of the study. W.H.P. reports serving as a consultant for Novo Nordisk outside the submitted work. R.S. reports personal fees from Novo Nordisk, Eli Lilly and AstraZeneca outside the submitted work. K.U. reports other financial activities with Novo Nordisk and Astra Zeneca outside the submitted work. T.H. has nothing to disclose. J.H.‐B. reports being previously employed by Novo Nordisk. S.T. has nothing to disclose. M.J.D. reports personal fees from Novo Nordisk, Sanofi‐Aventis, Lilly, Merck Sharp & Dohme, Boehringer Ingelheim, AstraZeneca, Janssen, Servier, Mitsubishi Tanabe Pharma Corporation and Takeda Pharmaceuticals International Inc., and grants from Novo Nordisk, Sanofi‐Aventis, Lilly, Boehringer Ingelheim and Janssen, all outside the submitted work.

© 2019 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.

Figures

Figure 1

(A) Change in overall treatment satisfaction score from baseline to end of treatment and (B) proportion of patients achieving improvements in overall treatment satisfaction (≥MIC) from baseline to end of treatment. *P < 0.05, **P < 0.01, ***P < 0.001 for semaglutide versus comparator. Overall treatment satisfaction as measured by DTSQ scores ranging from 0 to 36, where higher scores indicate better satisfaction. Bars may appear larger or smaller than the number indicated because of rounding to one decimal point. Mean observed values are based on the FAS and LOCF imputed data. For SUSTAIN 2–5, postbaseline data were analyzed using an ANCOVA model with treatment, country and stratum as fixed factors and baseline value as covariate. Mean estimates were adjusted according to observed baseline distribution. For SUSTAIN 7, postbaseline data were analyzed using an MMRM with treatment and country as fixed factors and baseline value as covariate, all nested within visit. MIC is calculated as 0.5×SD of the baseline score28,29 for each individual trial. Baseline SD is calculated from all non‐missing items for the FAS. Values for sitagliptin (SUSTAIN 2) and placebo (SUSTAIN 5) are pooled (mean) values. Abbreviations: ANCOVA, analysis of covariance; DTSQ, Diabetes Treatment Satisfaction Questionnaire; exenatide ER, exenatide extended release; FAS, full analysis set; IGlar, insulin glargine; LOCF, last observation carried forward; MIC, minimally important change; MMRM, mixed model for repeated measurements; SD, standard deviation

Figure 2

Change in (A) perceived hyperglycaemia and (B) hypoglycaemia from baseline to end of treatment. *P < 0.05, **P < 0.01, ***P < 0.001 for semaglutide versus comparator. Patients responded on a scale of 0–6 to the question ‘How often have you felt that your blood sugars have been unacceptably high/low recently?’ where 0 was the fewest times and 6 was the most times. Observed ‘on‐treatment without rescue medication data’. Bars may appear larger or smaller than the number indicated because of rounding to one decimal point. For SUSTAIN 2–5, postbaseline data were analyzed using an ANCOVA model with treatment, country and stratum as fixed factors and baseline value as covariate. Mean estimates were adjusted according to observed baseline distribution. For SUSTAIN 7, postbaseline data were analyzed using an MMRM with treatment and country as fixed factors and baseline value as covariate, all nested within visit. Abbreviations: ANCOVA, analysis of covariance; DTSQ, Diabetes Treatment Satisfaction Questionnaire; exenatide ER, exenatide extended release; IGlar, insulin glargine; MMRM, mixed model for repeated measurements

Figure 3

Change in overall treatment satisfaction score from baseline to end of treatment by the presence or absence of GI AEs in (A) SUSTAIN 2, (B) SUSTAIN 3, (C) SUSTAIN 4, (D) SUSTAIN 5 and (E) SUSTAIN 7. *P < 0.05 for semaglutide versus comparator within subgroup; no significant differences were observed in change from baseline with GI AEs and without GI AEs for each treatment arm. Treatment satisfaction as measured by DTSQ scores ranging from 0 to 6, where higher scores indicate better satisfaction. Bars may appear larger or smaller than the number indicated because of rounding to one decimal point. Only trial completers are included in the analysis. Number of patients in each trial are those exposed to at least one dose of trial drug who did not receive rescue medication. For SUSTAIN 2–5, postbaseline data were analyzed using an ANCOVA model with treatment, country and stratum as fixed factors and baseline value as covariate. Mean estimates were adjusted according to observed baseline distribution. For SUSTAIN 7, postbaseline data were analyzed using an MMRM with treatment and country as fixed factors and baseline value as covariate, all nested within visit. Abbreviations: AE, adverse event; ANCOVA, analysis of covariance; DTSQ, Diabetes Treatment Satisfaction Questionnaire; exenatide ER, exenatide extended release; GI, gastrointestinal; IGlar, insulin glargine; MMRM, mixed model for repeated measurements

Figure 4

Change in overall treatment satisfaction score from baseline to end of treatment in patients who did or did not achieve WL ≥ 5% in (A) SUSTAIN 2, (B) SUSTAIN 3, (C) SUSTAIN 4, (D) SUSTAIN 5 and (E) SUSTAIN 7. *P < 0.05 for semaglutide versus comparator within subgroup; †P < 0.05 for difference in change from baseline between patients who achieved ≥5% WL versus those with WL < 5% for each treatment arm. Treatment satisfaction as measured by DTSQ scores ranging from 0 to 6, where higher scores indicate better satisfaction. Bars may appear larger or smaller than the number indicated because of to rounding to one decimal point. Only trial completers are included in the analysis. Number of patients in each trial are those exposed to at least one dose of the trial drug who did not receive rescue medication. For SUSTAIN 2–5, postbaseline data were analyzed using an ANCOVA model with treatment, country and stratum as fixed factors and baseline value as covariate. Mean estimates were adjusted according to observed baseline distribution. For SUSTAIN 7, postbaseline data were analyzed using an MMRM with treatment and country as fixed factors and baseline value as covariate, all nested within visit. Abbreviations: ANCOVA, analysis of covariance; DTSQ, Diabetes Treatment Satisfaction Questionnaire; exenatide ER, exenatide extended release; IGlar, insulin glargine; MMRM, mixed model for repeated measurements; WL, weight loss

Figure 5

Change in overall treatment satisfaction from baseline to end of treatment in patients who did or did not achieve HbA1c P < 0.05 for semaglutide versus comparator within subgroup. †P < 0.05 for difference in change from baseline between patients with HbA1c < 7% and HbA1c ≥ 7% for each treatment arm. Treatment satisfaction as measured by DTSQ scores ranging from 0 to 6, where higher scores indicate better satisfaction. Bars may appear larger or smaller than the number indicated because of rounding to one decimal point. Only trial completers are included in the analysis. Number of patients in each trial are those exposed to at least one dose of trial drug who did not receive rescue medication. For SUSTAIN 2–5, postbaseline data were analyzed using an ANCOVA model with treatment, country and stratum as fixed factors and baseline value as covariate. Mean estimates were adjusted according to observed baseline distribution. For SUSTAIN 7, postbaseline data were analyzed using an MMRM with treatment and country as fixed factors and baseline value as covariate, all nested within visit. Abbreviations: ANCOVA, analysis of covariance; DTSQ, Diabetes Treatment Satisfaction Questionnaire; exenatide ER, exenatide extended release; IGlar, insulin glargine; MMRM, mixed model for repeated measurements