Graphical approaches for multiple comparison procedures using weighted Bonferroni, Simes, or parametric tests. Pratley R, Amod A, Tetens S, et al., on behalf of the PIONEER 4 Investigators. 0001).
Safety and tolerability of oral semaglutide were similar to subcutaneous liraglutide. 2020 Sep;11(9):1965-1982. doi: 10.1007/s13300-020-00894-y.

Notably, patients randomized to oral semaglutide lost more weight by week 26 than patients receiving liraglutide [-4.4 kg vs -3.1 kg, ETD -1.2 kg, 95% CI -1.9 to -0.6; P=0.0003] and placebo [ETD -3.8 kg, 95% CI -4.7 to -3.0; P<0.0001] when assessed using an intention-to-treat analysis.

In PIONEER 7, 21% of people treated with oral semaglutide experienced nausea, compared to 2% of people treated with sitagliptin. Efficacy and safety of glucagon-like peptide-1 receptor agonists in type 2 diabetes: A systematic review and mixed-treatment comparison analysis. Epub 2019 Jul 4. Management of hyperglycemia in type 2 diabetes: a patient-centered approach. with type 2 diabetes from 100 sites in 12 countries. A summary of the PIONEER 4 trial: Oral semaglutide versus subcutaneous liraglutide and placebo in type 2 diabetes Analisa Buysse, PharmD, Avera Marshall Regional Medical Center Background: Glucagon-like peptide-1 (GLP-1) agonists have become commonplace in the treatment of type 2 diabetes. The primary outcome was the change in HbA1c from baseline to 26 weeks. 2019 Jul 6;394(10192):4-6. doi: 10.1016/S0140-6736(19)31350-9.  |  A notable secondary endpoint included the change in body weight from baseline to week 26. Ann Intern Med. Adverse events were more frequent with oral semaglutide (n=229 [80%]) and subcutaneous liraglutide (n=211 [74%]) than with placebo (n=95 [67%]).

Congenital Heart Disease and Pediatric Cardiology, Invasive Cardiovascular Angiography and Intervention, Pulmonary Hypertension and Venous Thromboembolism, CardioSource Plus for Institutions and Practices, Nuclear Cardiology and Cardiac CT Meeting on Demand, Annual Scientific Session and Related Events, ACC Quality Improvement for Institutions Program, National Cardiovascular Data Registry (NCDR), Examination of Cardiovascular Outcomes With Alogliptin Versus Standard of Care, United Kingdom Prospective Diabetes Study, Saxagliptin Assessment of Vascular Outcomes Recorded in Patients With Diabetes Mellitus–Thrombolysis in Myocardial Infarction 53, Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients, Trial to Evaluate Cardiovascular and Other Long-term Outcomes With Semaglutide in Subjects With Type 2 Diabetes, Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results, Peptide Innovation for Early Diabetes Treatment 6, Congenital Heart Disease and     Pediatric Cardiology, Invasive Cardiovascular Angiography    and Intervention, Pulmonary Hypertension and Venous     Thromboembolism, Any medication for diabetes or obesity within 90 days of screening (other than metformin, sodium-glucose co-transporter-2 [SGLT2] inhibitor, or short-term insulin [≤14 days]), Renal impairment (estimated glomerular filtration rate <60 ml/min per 1.73 m, Proliferative retinopathy or maculopathy requiring acute treatment, Weight loss at 26 weeks: -4.4 kg vs. -3.1 kg vs. -0.5 kg (p = 0.003 for semaglutide vs. liraglutide; p < 0.0001 for semaglutide vs. placebo), Change in HbA1c at 52 weeks: -1.2% vs. -0.9% vs. -0.2% (p = 0.0002 for semaglutide vs. liraglutide; p < 0.0001 for semaglutide vs. placebo), Severe or symptomatic hypoglycemia: 1% vs. 2% vs. 1%, Gastrointestinal (GI) side effects: 8% vs. 6% vs. 2%.

In their respective cardiovascular outcomes trials, both agents have demonstrated a favorable cardiovascular profile, but the former issue may limit patient uptake. Approximately one quarter of patients were receiving an SGLT2 inhibitor at baseline. Liraglutide versus sitagliptin for patients with type 2 diabetes who did not have adequate glycaemic control with metformin: a 26-week, randomised, parallel-group, open-label trial.

 |  Alpha was set at 0.05. eligible and randomly assigned to oral semaglutide (n=285), subcutaneous liraglutide Lancet. A Review on Semaglutide: An Oral Glucagon-Like Peptide 1 Receptor Agonist in Management of Type 2 Diabetes Mellitus.  |  Liraglutide and cardiovascular outcomes in type 2 diabetes. Two distinct statistical approaches to evaluate the effects of oral semaglutide were applied in the PIONEER 4 and 7 trials; a primary statistical approach[1] required by recent regulatory guidance, evaluating the effect regardless of discontinuation of treatment and use of rescue medication, and a secondary statistical approach[2] describing the effect while on treatment and without use of rescue medication. Patients were randomized in a 2:2:1 fashion to oral semaglutide (n = 285), subcutaneous liraglutide (n = 284), or placebo (n = 142) once-daily in addition to existing background glucose-lowering medication. PIONEER 4 provides evidence for orally administered semaglutide 14 mg vs a GLP-1 RA in patients inadequately controlled on 1–2 OADs, showing significantly greater reductions in HbA 1c and body weight with orally administered semaglutide 14 mg compared with liraglutide and placebo (both treatments + metformin ± sodium/glucose cotransporter 2 inhibitor, SGLT2i) . "At the same time, we have shown that oral semaglutide is even more efficacious in lowering glucose and body weight than the most widely used injectable GLP-1 treatment, Victoza®". doi: 10.1016/S0140-6736(19)31519-3. NIH In the trial, oral semaglutide was well-tolerated and with a profile consistent with GLP-1-based therapy.

PIONEER 4 (NCT02863419), which was simultaneously published in The Lancet, 11 was a comparative study of 14 mg oral semaglutide, liraglutide, the most widely used injectable GLP-1 agonist, and placebo in 711 people with T2D inadequately controlled on metformin, with or without an SGLT-2 inhibitor. Clinical Topics: Diabetes and Cardiometabolic Disease, Prevention, Keywords: Blood Glucose, Diabetes Mellitus, Type 2, Glucagon-Like Peptides, Glucose, Hemoglobin A, Hypoglycemia, Metabolic Syndrome X, Metformin, Primary Prevention, Weight Loss. In PIONEER 4, 20% of people treated with oral semaglutide experienced nausea, compared to 18% of people treated with Victoza® and 4% of people treated with placebo. The reduction in body weight of 2.9 kg with oral semaglutide was statistically significantly greater at week 52 compared to 0.8 kg with sitagliptin.

View this presentation at ADA2020.org, Not yet registered? Statistical principles for clinical trials E9. Semaglutide: Charting New Horizons in GLP-1 Analogue Outcome Studies. Note: More than 45 presenters submitted articles previewing their Virtual 80th Scientific Sessions presentations. This phase 3a trial, PIONEER 4, is the first to compare the efficacy and safety of oral semaglutide with a subcutaneously injected GLP-1 receptor agonist, liraglutide, and placebo in patients with type 2 diabetes uncontrolled on background metformin with or without a sodium-glucose co … Effects of semaglutide on risk of cardiovascular events across a continuum of cardiovascular risk: combined post hoc analysis of the SUSTAIN and PIONEER trials. Husain M, Bain SC, Holst AG, Mark T, Rasmussen S, Lingvay I. Cardiovasc Diabetol.