Efficacy, Safety, and Tolerability of Oral Semaglutide Versus Placebo Added to Insulin With or Without Metformin in Patients With Type 2 Diabetes: The PIONEER 8 Trial

Zinman, Bernard; Aroda, Vanita R.; Buse, John B.; Cariou, Bertrand; Harris, Stewart B.; Hoff, Søren T.; Pedersen, Karen Boje; Tarp-Johansen, Mads Jeppe; Araki, Eiichi

doi:10.2337/dc19-0898

Cited by 162 publications

(296 citation statements)

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“…Oral semaglutide, either as monotherapy or as add‐on treatment, was compared with placebo in six trials, and with other glucose‐lowering agents (liraglutide, semaglutide weekly, sitagliptin and empagliflozin) in five trials . Notably, from a phase 2 dose‐finding trial, we extracted data for safety outcomes from the 2.5, 5 and 10 mg arms, while for two trials initially identified as conference abstracts, we used additional data from subsequently published full text reports . All of the studies had a parallel group design and seven of them were double‐blind .…”

Section: Resultsmentioning

confidence: 99%

“…22,23 The characteristics of trials included in the meta-analysis and participants' baseline characteristics are summarized in Table 1. Oral semaglutide, either as monotherapy or as add-on treatment, was compared with placebo in six trials, [24][25][26][27][28][29] and with other glucose-lowering agents (liraglutide, semaglutide weekly, sitagliptin and empagliflozin) in five trials. 27,[29][30][31][32] Notably, from a phase 2 dose-finding trial, we extracted data for safety outcomes from the 2.5, 5 and 10 mg arms, 29 while for two trials initially identified as conference abstracts, we used additional data from subsequently published full text reports.…”

Section: Search Results and Study Characteristicsmentioning

confidence: 99%

“…27,[29][30][31][32] Notably, from a phase 2 dose-finding trial, we extracted data for safety outcomes from the 2.5, 5 and 10 mg arms, 29 while for two trials initially identified as conference abstracts, we used additional data from subsequently published full text reports. 28,30 All of the studies had a parallel group design and seven of them were doubleblind. [24][25][26][27][28][29]32 Study duration ranged from 12 to 72 weeks.…”

Section: Search Results and Study Characteristicsmentioning

confidence: 99%

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Oral semaglutide for type 2 diabetes: A systematic review and meta‐analysis

Avgerinos

Michailidis

Liakos

et al. 2019

Diabetes Obesity Metabolism

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Aim To assess the efficacy and safety of oral semaglutide, a novel glucagon‐like peptide‐1 receptor agonist, for patients with type 2 diabetes. Methods We searched Medline, Embase, the Cochrane Library and grey literature sources up to July 1, 2019 for randomized controlled trials (RCTs) comparing oral semaglutide with placebo or other antidiabetic agents. The primary outcome was change from baseline in HbA1c. Secondary outcomes included change from baseline in body weight and blood pressure, cardiovascular endpoints, severe hypoglycaemia, gastrointestinal adverse events and diabetic retinopathy. We synthesized results using weighted mean differences (WMDs) for continuous outcomes and odds ratios (ORs) for dichotomous outcomes, along with 95% confidence intervals (CIs). Results We included 11 RCTs with 9890 patients in the systematic review. Compared with placebo, oral semaglutide reduced HbA1c and body weight (WMD –0.89%, 95% CI −1.07 to −0.71 and − 2.99 kg, 95% CI −3.69 to −2.30, respectively). Oral semaglutide was also superior to other active comparators (including liraglutide, empagliflozin and sitaglipitin) in terms of lowering HbA1c (WMD –0.35%, 95% CI −0.43 to −0.26) and reduction of body weight (WMD −1.48 kg, 95% CI −2.28 to −0.67), and had a favourable effect on systolic blood pressure. Compared with placebo, oral semaglutide reduced all‐cause mortality (OR 0.58, 95% CI 0.37 to 0.92) and cardiovascular mortality (OR 0.55, 95% CI 0.31 to 0.98), and had a neutral effect on myocardial infarction, stroke, severe hypoglycaemia and diabetic retinopathy. However, treatment with oral semaglutide increased the incidence of nausea, vomiting and diarrhea, while events of acute pancreatitis were rare. Conclusions Oral semaglutide can effectively and safely reduce blood glucose, body weight and systolic blood pressure. Nevertheless, it is associated with increased incidence of gastrointestinal adverse events. Further research is needed to clarify its long‐term safety and comparative effectiveness against other antidiabetic agents.

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Section: Resultsmentioning

confidence: 99%

Section: Search Results and Study Characteristicsmentioning

confidence: 99%

Section: Search Results and Study Characteristicsmentioning

confidence: 99%

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Oral semaglutide for type 2 diabetes: A systematic review and meta‐analysis

Avgerinos

Michailidis

Liakos

et al. 2019

Diabetes Obesity Metabolism

Self Cite

View full text Add to dashboard Cite

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“…The half‐life (~7 days) and clinical effects of semaglutide are similar irrespective of mode of administration . Both formulations lowered HbA1c and body weight versus comparators across the continuum of care in subjects with T2D in the SUSTAIN (s.c.) and PIONEER (oral) phase 3a clinical trial programmes.…”

Section: Introductionmentioning

confidence: 99%

Semaglutide (SUSTAIN and PIONEER) reduces cardiovascular events in type 2 diabetes across varying cardiovascular risk

Husain

Bain

Jeppesen

et al. 2020

Diabetes Obesity Metabolism

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111

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Aim To investigate the effects of semaglutide versus comparators on major adverse cardiovascular events (MACE: cardiovascular [CV] death, nonfatal myocardial infarction [MI] and nonfatal stroke) and hospitalization for heart failure (HF) in the SUSTAIN (subcutaneous semaglutide) and PIONEER (oral semaglutide) trials across subgroups of varying CV risk. Methods Post hoc analyses of individual patient‐level data combined from SUSTAIN 6 and PIONEER 6 were performed to assess MACE and HF. MACE were analysed in subjects with and without: established CV disease and/or chronic kidney disease; prior MI or stroke; and prior HF. MACE in the SUSTAIN and PIONEER glycaemic efficacy trials were also assessed. Results In SUSTAIN 6 and PIONEER 6 combined, the hazard ratio (HR) for effect of semaglutide versus placebo on overall MACE was 0.76 (95% CI 0.62, 0.92), which was mainly driven by the effect on nonfatal stroke (HR 0.65 [95% CI 0.43, 0.97]). The HR for hospitalization for HF was 1.03 (95% CI 0.75, 1.40). The HRs for MACE were <1.0 in all subgroups, except for those with prior HF (HR 1.06 [95% CI 0.72, 1.57]); P‐values for interaction of subgroup on treatment effect were >0.05, except for HF (0.046). In the combined glycaemic efficacy trials, the HR for effect of semaglutide versus comparators on MACE was 0.85 (95% CI 0.55, 1.33). Conclusions In SUSTAIN and PIONEER combined, glucagon‐like peptide‐1 analogue semaglutide showed consistent effects on MACE versus comparators across varying CV risk. No effect of semaglutide on MACE was observed in subjects with prior HF.

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“…Liraglutide is currently being trialled in PWS by many research groups worldwide, and the research team led by Professor Paul Hofman at the University of Auckland has observed significant weight loss in their paediatric patients (NCT02527200) . The advent of a potent oral formulation of the GLP‐1 receptor agonist setmelanotide which was recently FDA approved for patients with T2DM offers additional promise …”

Section: Resultsmentioning

confidence: 99%

Current and emerging therapies for managing hyperphagia and obesity in Prader‐Willi syndrome: A narrative review

et al. 2019

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Summary In early childhood, individuals with Prader‐Willi syndrome (PWS) experience excess weight gain and severe hyperphagia with food compulsivity, which often leads to early onset morbid obesity. Effective treatments for appetite suppression and weight control are currently unavailable for PWS. Our aim to further understand the pathogenesis of PWS led us to carry out a comprehensive search of the current and emerging therapies for managing hyperphagia and extreme weight gain in PWS. A literature search was performed using PubMed and the following keywords: “PWS” AND “therapy” OR “[drug name]”; reference lists, pharmaceutical websites, and the ClinicalTrials.gov registry were also reviewed. Articles presenting data from current standard treatments in PWS and also clinical trials of pharmacological agents in the pipeline were selected. Current standard treatments include dietary restriction/modifications, exercise, and growth hormone replacement, which appear to have limited efficacy for appetite and weight control in patients with PWS. The long‐term safety and effectiveness of bariatric surgery in PWS remains unknown. However, many promising pharmacotherapies are in development and, if approved, will bring much needed choices into the PWS pharmacological armamentarium. With the progress that is currently being made in our understanding of PWS, an effective treatment may not be far off.

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Efficacy, Safety, and Tolerability of Oral Semaglutide Versus Placebo Added to Insulin With or Without Metformin in Patients With Type 2 Diabetes: The PIONEER 8 Trial

Cited by 162 publications

References 28 publications

Oral semaglutide for type 2 diabetes: A systematic review and meta‐analysis

Oral semaglutide for type 2 diabetes: A systematic review and meta‐analysis

Semaglutide (SUSTAIN and PIONEER) reduces cardiovascular events in type 2 diabetes across varying cardiovascular risk

Current and emerging therapies for managing hyperphagia and obesity in Prader‐Willi syndrome: A narrative review

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