Oral semaglutide versus subcutaneous liraglutide and placebo in type 2 diabetes (PIONEER 4): a randomised, double-blind, phase 3a trial

Pratley, Richard E.; Amod, Aslam; Hoff, Søren T.; Kadowaki, Takashi; Lingvay, Ildiko; Nauck, Michael A.; Pedersen, Karen Boje; Saugstrup, Trine; investigators, Pioneer

doi:10.1016/s0140-6736(19)31271-1

Cited by 384 publications

(511 citation statements)

References 15 publications

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“…The characteristics of trials included in the meta‐analysis and participants' baseline characteristics are summarized in Table . 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 .…”

Section: Resultsmentioning

confidence: 99%

“…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 . Study duration ranged from 12 to 72 weeks.…”

Section: Resultsmentioning

confidence: 99%

“…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. 28,30 All of the studies had a parallel group design and seven of them were doubleblind.…”

Section: Search Results and Study Characteristicsmentioning

confidence: 99%

“…Available data for treatment with oral semaglutide provide consistent evidence of both its glycaemic and non‐glycaemic beneficial effects in patients with T2D that is in line with trial findings for injectable GLP‐1 receptor agonists. Notably, oral semaglutide outperformed liraglutide in terms of glycaemic control and weight loss based on findings from a single head‐to‐head trial against injectable GLP‐1 therapies . The ADA/EASD consensus statement for the management of hyperglycaemia in patients with T2D suggests the use of GLP‐1 receptor agonists in patients with established or at high risk of atherosclerotic cardiovascular disease .…”

Section: Discussionmentioning

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: Resultsmentioning

confidence: 99%

Section: Search Results and Study Characteristicsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

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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“…Weight loss was similar in both groups in the intention‐to‐treat analysis. Additionally, Dr Richard Pratley (AdventHealth Translational Research Institute for Diabetes and Metabolism, Orlando, Florida) presented full results from PIONEER 4 (N = 711) comparing oral semaglutide 14 mg to injectable liraglutide 1.8 mg . At 26 weeks, oral semaglutide was noninferior on HbA1c lowering (−1.2% vs −1.1% for oral semaglutide vs liraglutide) and superior on weight loss (−4.4 kg vs −3.1 kg).…”

Section: American Diabetes Association 79th Scientific Session Diabetmentioning

confidence: 99%

Diabetes news

Biba

Teng

Kurian

et al. 2019

Journal of Diabetes

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Ursula Biba, Rhea W. Teng, Martin J. Kurian, Ann M. Carracher, and Kelly L. Close are of Close Concerns (http://www.closeconcerns.com), a healthcare information company focused exclusively on diabetes and obesity care. Close Concerns publishes Closer Look, a periodical that brings together news and insights in these areas. Each month, the Journal of Diabetes includes this News feature, in which Biba, Teng, Kurian, Carracher, and Close review the latest developments relevant to researchers and clinicians.

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