Dataset Information

Efficacy and safety of once-weekly semaglutide in Japanese individuals with type 2 diabetes in the SUSTAIN 1, 2, 5 and 9 trials: Post-hoc analysis.

ABSTRACT:

Aims/introduction

The etiology and treatment of type 2 diabetes might differ between specific populations. This post-hoc exploratory analysis assessed the efficacy and safety of once-weekly subcutaneous semaglutide vs comparators in Japanese individuals with type 2 diabetes in comparison with the total population from four phase III studies in the Trial to Evaluate Cardiovascular and Other Long-term Outcomes with Semaglutide in Subjects with Type 2 Diabetes (SUSTAIN) program.

Materials and methods

This analysis was carried out with data from the SUSTAIN 1, 2, 5 and 9 trials. Post-hoc analyses were carried out to assess outcomes in all participants and in Japanese participants in each study. The primary end-point was the change from baseline to end of study in glycated hemoglobin (%). The confirmatory secondary end-point was change from baseline to end of study in bodyweight (kg).

Results

Change from baseline to end of study in glycated hemoglobin with once-weekly semaglutide ranged from -1.32 to -1.85% points in the overall populations, and -1.69 to -2.49% points in Japanese participants. With once-weekly semaglutide, relative bodyweight was reduced from baseline to end of study by 4.0-7.3% in the overall populations, and 2.7-10.4% in Japanese participants. In the Japanese subpopulation, no new safety concerns were identified with once-weekly semaglutide, and there were no adverse events leading to death or severe hypoglycemic episodes.

Conclusions

In this post-hoc analysis, participants with type 2 diabetes initiating once-weekly semaglutide experienced improvements in glycated hemoglobin and bodyweight in both the overall and Japanese population, and no new safety concerns were identified among Japanese participants, supporting the efficacy of once-weekly semaglutide in this population.

SUBMITTER: Araki E

PROVIDER: S-EPMC9720207 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature

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Efficacy and safety of once-weekly semaglutide in Japanese individuals with type 2 diabetes in the SUSTAIN 1, 2, 5 and 9 trials: Post-hoc analysis.

Araki Eiichi E Harashima Shinichi S Nishida Tomoyuki T Nakamura Jiro J

Journal of diabetes investigation 20221012 12

<h4>Aims/introduction</h4>The etiology and treatment of type 2 diabetes might differ between specific populations. This post-hoc exploratory analysis assessed the efficacy and safety of once-weekly subcutaneous semaglutide vs comparators in Japanese individuals with type 2 diabetes in comparison with the total population from four phase III studies in the Trial to Evaluate Cardiovascular and Other Long-term Outcomes with Semaglutide in Subjects with Type 2 Diabetes (SUSTAIN) program.<h4>Material ...[more]

PMID: 36222597

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Project description:ObjectiveIn SUSTAIN 7, once-weekly semaglutide demonstrated superior glycated haemoglobin (HbA1c) and body weight (BW) reductions versus once-weekly dulaglutide in subjects with type 2 diabetes (T2D). This post hoc analysis investigated the impact of clinically relevant subject characteristics on treatment effects of semaglutide versus dulaglutide.DesignAnalyses by baseline age (<65, ≥65 years), sex (male, female), diabetes duration (≤5, >5-10, >10 years), HbA1c (≤7.5, >7.5-8.5, >8.5% (≤58, >58-69, >69 mmol/mol)) and body mass index (BMI) (<30, 30-<35, ≥35 kg/m2).Setting194 sites; 16 countries.ParticipantsSubjects with T2D (n=1199) exposed to treatment.InterventionsSemaglutide 0.5 mg versus dulaglutide 0.75 mg (low-dose comparison); semaglutide 1.0 mg versus dulaglutide 1.5 mg (high-dose comparison), all subcutaneously once weekly.Primary and secondary outcome measuresChange in HbA1c (primary endpoint) and BW (confirmatory secondary endpoint) from baseline to week 40; proportion of subjects achieving HbA1c targets (<7%, ≤6.5% (<53, ≤48 mmol/mol)) and weight-loss responses (≥5%, ≥10%) at week 40; and safety.ResultsHbA1c and BW reductions (estimated treatment difference ranges: -0.22 to -0.70%-point; -1.76 to -3.84 kg) and proportion of subjects achieving HbA1c targets and weight-loss responses were statistically significantly greater for the majority of comparisons of semaglutide versus dulaglutide within each subgroup category and, excepting glycaemic control within the low-dose comparison in HbA1c subgroups, this was irrespective of subgroup or dose comparison. Gastrointestinal adverse events, the most common with both treatments, were reported by more women than men and, with semaglutide, decreased with increasing BMI.ConclusionsConsistently greater improvements in HbA1c and BW with semaglutide versus dulaglutide, regardless of age, sex, diabetes duration, glycaemic control and BMI, support the efficacy of semaglutide across the continuum of care in a heterogeneous population with T2D.Trial registration numberNCT02648204.

Project description: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).

Project description:AimsTo assess the safety and efficacy of monotherapy with once-weekly subcutaneous (s.c.) semaglutide vs sitagliptin in Japanese people with type 2 diabetes (T2D).MethodsIn this phase IIIa randomized, open-label, parallel-group, active-controlled, multicentre trial, Japanese adults with T2D treated with diet and exercise only or oral antidiabetic drug monotherapy (washed out during the run-in period) received once-weekly s.c. semaglutide (0.5 or 1.0 mg) or once-daily oral sitagliptin 100 mg. The primary endpoint was number of treatment-emergent adverse events (TEAEs) after 30 weeks.ResultsOverall, 308 participants were randomized and exposed to treatment, with similar baseline characteristics across the groups. In total, 2.9% of participants in both the semaglutide 0.5 mg and the sitagliptin group prematurely discontinued treatment, compared with 14.7% in the semaglutide 1.0 mg group. The majority of discontinuations in the semaglutide 0.5 and 1.0 mg groups were attributable to adverse events (AEs). More TEAEs were reported in semaglutide- vs sitagliptin-treated participants (74.8%, 71.6% and 66.0% in the semaglutide 0.5 mg, semaglutide 1.0 mg and sitagliptin groups, respectively). AEs were mainly mild to moderate. Gastrointestinal AEs, most frequently reported with semaglutide, diminished in frequency over time. The mean glycated haemoglobin (HbA1c [baseline 8.1%]) decreased by 1.9% and 2.2% with semaglutide 0.5 and 1.0 mg, respectively, vs 0.7% with sitagliptin (estimated treatment difference [ETD] vs sitagliptin -1.13%, 95% confidence interval [CI] -1.32; -0.94, and -1.44%, 95% CI -1.63; -1.24; both P < .0001). Body weight (baseline 69.3 kg) was reduced by 2.2 and 3.9 kg with semaglutide 0.5 and 1.0 mg, respectively (ETD -2.22 kg, 95% CI -3.02; -1.42 and -3.88 kg, 95% CI -4.70; -3.07; both P < .0001).ConclusionsIn Japanese people with T2D, more TEAEs were reported with semaglutide than with sitagliptin; however, the semaglutide safety profile was similar to that of other glucagon-like peptide-1 receptor agonists. Semaglutide significantly reduced HbA1c and body weight compared with sitagliptin.

Project description:BackgroundA once-weekly, 2.4-mg dose of subcutaneous semaglutide, a glucagon-like peptide-1 receptor agonist, is used to treat obesity in adults, but assessment of the drug in adolescents has been lacking.MethodsIn this double-blind, parallel-group, randomized, placebo-controlled trial, we enrolled adolescents (12 to <18 years of age) with obesity (a body-mass index [BMI] in the 95th percentile or higher) or with overweight (a BMI in the 85th percentile or higher) and at least one weight-related coexisting condition. Participants were randomly assigned in a 2:1 ratio to receive once-weekly subcutaneous semaglutide (at a dose of 2.4 mg) or placebo for 68 weeks, plus lifestyle intervention. The primary end point was the percentage change in BMI from baseline to week 68; the secondary confirmatory end point was weight loss of at least 5% at week 68.ResultsA total of 201 participants underwent randomization, and 180 (90%) completed treatment. All but one of the participants had obesity. The mean change in BMI from baseline to week 68 was -16.1% with semaglutide and 0.6% with placebo (estimated difference, -16.7 percentage points; 95% confidence interval [CI], -20.3 to -13.2; P<0.001). At week 68, a total of 95 of 131 participants (73%) in the semaglutide group had weight loss of 5% or more, as compared with 11 of 62 participants (18%) in the placebo group (estimated odds ratio, 14.0; 95% CI, 6.3 to 31.0; P<0.001). Reductions in body weight and improvement with respect to cardiometabolic risk factors (waist circumference and levels of glycated hemoglobin, lipids [except high-density lipoprotein cholesterol], and alanine aminotransferase) were greater with semaglutide than with placebo. The incidence of gastrointestinal adverse events was greater with semaglutide than with placebo (62% vs. 42%). Five participants (4%) in the semaglutide group and no participants in the placebo group had cholelithiasis. Serious adverse events were reported in 15 of 133 participants (11%) in the semaglutide group and in 6 of 67 participants (9%) in the placebo group.ConclusionsAmong adolescents with obesity, once-weekly treatment with a 2.4-mg dose of semaglutide plus lifestyle intervention resulted in a greater reduction in BMI than lifestyle intervention alone. (Funded by Novo Nordisk; STEP TEENS ClinicalTrials.gov number, NCT04102189.).

Project description:Background: Semaglutide, a newly once-weekly glucagon like peptide-1 (GLP-1) receptor agonist, has showed a favorable effect on glycaemic control and weight reduction in type 2 diabetes mellitus (T2DM). This meta-analysis was conducted to evaluate the clinical efficacy and safety of semaglutide in T2DM. Methods: A comprehensive searching was performed for Phase III randomized controlled trials (RCTs) which reported the efficacy and safety data of semaglutide and other therapies. The efficacy data expressed as weight mean difference (WMD) and the safety data expressed as risk ratios (RRs) were calculated by employing random-effects model. Heterogeneity was assessed through I2 test, and subgroup analyses were performed by different control groups, dosage of semaglutide, and durations of follow up. Results: 9 RCTs including 9,773 subjects met the inclusion criteria. For efficacy, compared with other therapies, semaglutide resulted in a significant reduction in glycosylated hemoglobin (weight mean difference, WMD: -0.93%, 95% CI: -1.24 to -0.62, P < 0.001), fasting plasma glucose (WMD: -1.15 mmol/L, 95% CI: -1.67 to -0.63, P < 0.001), mean self-monitoring of plasma glucose (WMD: -1.19 mmol/L, 95% CI: -1.68 to -0.70, P < 0.001), body weight (WMD: -3.47 kg, 95% CI: -3.96 to -2.98, P < 0.001), body mass index (WMD: -1.25 kg/m2, 95% CI: -1.45 to -1.04, P < 0.001), systolic blood pressure (WMD: -2.55 mmHg, 95% CI: -3.22 to -1.88, P < 0.001), with the exception of negative result of diastolic blood pressure (WMD: -0.29 mmHg, 95% CI: -0.65 to 0.07, P = 0.113) and increased impact on pulse rate (WMD: -2.21, 95% CI: 1.54 to 2.88, P < 0.001). The results were consistent across the key subgroups. For safety, semaglutide did not increase the risk of any adverse events, hypoglycemia and pancreatitis, but induced a higher risk of gastrointestinal disorders when compared with other therapies (RR: 1.98, 95%CI: 1.49 to 2.62, P < 0.001). Conclusion: Semaglutide was effective and acceptable in patients with T2DM except for a high risk of gastrointestinal disorders. The capacity of glycaemic and body weight control of semaglutide appeared more effective than other add-on therapies including other GLP-1 receptor agonists of exenatide release and dulaglutide.

Dataset Information

Efficacy and safety of once-weekly semaglutide in Japanese individuals with type 2 diabetes in the SUSTAIN 1, 2, 5 and 9 trials: Post-hoc analysis.

Aims/introduction

Materials and methods

Results

Conclusions

Publications

Efficacy and safety of once-weekly semaglutide in Japanese individuals with type 2 diabetes in the SUSTAIN 1, 2, 5 and 9 trials: Post-hoc analysis.

Similar Datasets

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