on In the PIONEER 2 trial, which investigated oral semaglutide versus Jardiance 25mg, the change from baseline HbA1c (8.1%) to week 52 was recorded for both study arms as -1.3% for 14mg oral semaglutide and -0.8% for Jardiance 25mg. In the current trial, diabetic retinopathy–related adverse events were more frequent with oral semaglutide compared with empagliflozin, although occurrence was low in both groups (3.4% vs. 1.2%).
The estimand reflects the effect of initiating treatment with oral semaglutide compared with initiating treatment with empagliflozin, both potentially followed by either discontinuation of trial product and/or addition of or switch to another glucose-lowering drug. But the drug is also approved and sold under the name Saxenda to treat weight loss — although most sales still come from the diabetes indication. With regulators, drugmakers and payers pulling in similar directions, real-world evidence is likely to become a more central feature of drug development despite its many shortcomings. S.Ø.L. Yet obesity has traditionally been a tough market to crack. * A complete list of investigators in the Peptide Innovation for Early Diabetes Treatment 2 trial (PIONEER 2) is provided in the Supplementary Data. This trial provides a comparison of two increasingly used drug classes that are commonly added to metformin when glycemic control is not achieved. Oral semaglutide is coformulated in a tablet with the absorption enhancer sodium N-(8-[2-hydroxylbenzoyl] amino) caprylate, which facilitates semaglutide absorption across the gastric mucosa (10). No other potential conflicts of interest relevant to this article were reported. 1 and Table 2, respectively. H.W.R. Search terms included semaglutide, glucagon-like peptide 1 receptor agonist, GLP-1 receptor agonist, and type 2 diabetes. The principal limitation of the trial was the open-label design. 9. Four hundred (97.1%) patients in the oral semaglutide group and 387 (94.4%) in the empagliflozin group completed the trial (Supplementary Fig. The most frequent adverse event with oral semaglutide was nausea, which was nonserious, usually mild to moderate severity and transient, and did not exceed a prevalence of 10% at any time (Table 3 and Supplementary Fig. Once-daily oral semaglutide demonstrated a significant dose-dependent glucose-lowering effect compared to placebo and the active comparators (Jardiance and Januvia). 1). 5). Injectable glucagon-like peptide 1 receptor agonists (GLP-1RAs) and oral sodium–glucose cotransporter 2 (SGLT-2) inhibitors are recommended as second-line therapy because of their ability to lower glucose without increasing hypoglycemia risk, weight loss effect, and associated cardiovascular benefits (1,2). The trial tested semaglutide against placebo and Novo's other glucagon-like peptide-1 (GLP-1) agonist Saxenda. OBJECTIVE Efficacy and safety of the glucagon-like peptide 1 (GLP-1) analog oral semaglutide and the sodium–glucose cotransporter 2 inhibitor empagliflozin were compared in patients with type 2 diabetes uncontrolled on metformin. J.G. Secondary end points included changes from baseline to week 52 in HbA1c and body weight (kg) and changes from baseline to weeks 26 and 52 in fasting plasma glucose, self-measured blood glucose (SMBG) profile (7-point profile and mean postprandial increment over all meals), fasting C-peptide, fasting insulin, fasting proinsulin, fasting glucagon, HOMA of insulin resistance (HOMA-IR), HOMA of β-cell function (HOMA-B), C-reactive protein, body weight (%), BMI, waist circumference, and fasting lipid profile.
Editor's Note: A previous version of this article mistakenly referred to Saxenda as Victoza.
The trial product estimand was estimated by a mixed model for repeated measurements that used data collected before premature trial product discontinuation or initiation of rescue medication from all randomized patients. Patients discontinuing oral semaglutide could not be switched to additional antidiabetic medication with a comparable weight-reducing effect, while patients on empagliflozin could be switched to GLP-1RAs. In a longer-term, 78-week, double-blind trial, no imbalance in the occurrence of diabetic retinopathy–related events was observed between oral semaglutide 3, 7, and 14 mg and sitagliptin (6.7%, 6.0%, 5.6%, and 7.7%, respectively) (15).
Attainment of ADA-recommended HbA1c targets at 26 and 52 weeks was also significantly greater with oral semaglutide.
This trial is investigating the long-term efficacy and safety of oral semaglutide, which is currently available on the market as Novo Nordisk’s subcutaneous injectable formulation, Ozempic.
RESULTS Four hundred (97.1%) patients in the oral semaglutide group and 387 (94.4%) in the empagliflozin group completed the trial. Patients were randomized (1:1) to once-daily oral semaglutide 14 mg or empagliflozin 25 mg for 52 weeks using an interactive web response system with a further 5 weeks of follow-up (Supplementary Fig.
Reductions in HbA1c were significantly greater with oral semaglutide at 52 weeks. I.L.
Editorial support was funded by the sponsor and provided by independent medical writers under the guidance of the authors. E: Estimated changes from baseline in body weight at weeks 26 and 52.
The treatment policy estimand evaluates the treatment effect for all randomized patients, regardless of trial product discontinuation or use of rescue medication. Author Contributions. The FLOW study is the ﬁrst dedicated GLP-1 analogue renal outcome trial in people with T2D, with the aim to determine whether semaglutide reduces adverse renal events in people with T2D and impaired renal function.
reports clinical research for Novo Nordisk, Janssen, Eli Lilly, and Sanofi and lecturing for Sanofi and Boehringer Ingelheim. In the empagliflozin group, 56 (13.7%) patients initiated additional antidiabetic medication, with this being rescue medication in 44 (10.7%). © 2019 by the American Diabetes Association. Parts of this study were presented in oral form at the 79th Scientific Sessions of the American Diabetes Association, San Francisco, CA, 7–11 June 2019. Semaglutide is a human GLP-1 analog currently available as a once-weekly injection associated with reduced glycated hemoglobin (HbA1c), weight loss, and fewer cardiovascular events in type 2 diabetes (3–9).
This trial is investigating the long-term efficacy and safety of oral semaglutide, which is currently available on the market as Novo Nordisk’s subcutaneous (SC) injectable formulation, Ozempic.
EOR, estimated odds ratio.
Two different questions related to the efficacy objectives were addressed through the definition of two estimands: treatment policy and trial product. Diabetic retinopathy–related adverse events were reported in 14 (3.4%) patients in the oral semaglutide group and in 5 (1.2%) in the empagliflozin group (in-trial period) (Supplementary Table 5). B: Estimated changes from baseline in HbA1c at weeks 26 and 52.
Data will be made available after research completion, approval of the product, and product use in the European Union and U.S.
Orexigen Therapeutics Inc. recently announced that it would file for chapter 11 bankruptcy after its obesity drug failed to ever take off.