Effect of Additional Oral Semaglutide vs Sitagliptin on Glycated Hemoglobin in Adults With Type 2 Diabetes Uncontrolled With Metformin Alone or With Sulfonylurea

Autor: Pierre Serusclat, Julio Rosenstock, Hirotaka Watada, Dale Allison, Thalia Marie Blicher, Jacob Bonde Jacobsen, Rafael Violante, Andreas L. Birkenfeld, Srikanth Deenadayalan, Melanie J. Davies
Rok vydání: 2019
Předmět:
Adult
Male
medicine.medical_specialty
Glucagon-Like Peptides
Administration
Oral
Type 2 diabetes
01 natural sciences
Gastroenterology
law.invention
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Double-Blind Method
Randomized controlled trial
Glucagon-Like Peptide 1
law
Internal medicine
Diabetes mellitus
Clinical endpoint
Humans
Hypoglycemic Agents
Medicine
030212 general & internal medicine
0101 mathematics
Original Investigation
Glycated Hemoglobin
Dose-Response Relationship
Drug
business.industry
Semaglutide
Body Weight
Sitagliptin Phosphate
010102 general mathematics
General Medicine
Middle Aged
medicine.disease
Metformin
Sulfonylurea Compounds
Diabetes Mellitus
Type 2
chemistry
Sitagliptin
Drug Therapy
Combination
Female
Glycated hemoglobin
business
medicine.drug
Zdroj: JAMA 321, 1466-1480 (2019)
ISSN: 0098-7484
Popis: IMPORTANCE: Phase 3 trials have not compared oral semaglutide, a glucagon-like peptide 1 receptor agonist, with other classes of glucose-lowering therapy. OBJECTIVE: To compare efficacy and assess long-term adverse event profiles of once-daily oral semaglutide vs sitagliptin, 100 mg added on to metformin with or without sulfonylurea, in patients with type 2 diabetes. DESIGN, SETTING, AND PARTICIPANTS: Randomized, double-blind, double-dummy, parallel-group, phase 3a trial conducted at 206 sites in 14 countries over 78 weeks from February 2016 to March 2018. Of 2463 patients screened, 1864 adults with type 2 diabetes uncontrolled with metformin with or without sulfonylurea were randomized. INTERVENTIONS: Patients were randomized to receive once-daily oral semaglutide, 3 mg (n = 466), 7 mg (n = 466), or 14 mg (n = 465), or sitagliptin, 100 mg (n = 467). Semaglutide was initiated at 3 mg/d and escalated every 4 weeks, first to 7 mg/d then to 14 mg/d, until the randomized dosage was achieved. MAIN OUTCOMES AND MEASURES: The primary end point was change in glycated hemoglobin (HbA(1c)), and the key secondary end point was change in body weight, both from baseline to week 26. Both were assessed at weeks 52 and 78 as additional secondary end points. End points were tested for noninferiority with respect to HbA(1c) (noninferiority margin, 0.3%) prior to testing for superiority of HbA(1c) and body weight. RESULTS: Among 1864 patients randomized (mean age, 58 [SD, 10] years; mean baseline HbA(1c), 8.3% [SD, 0.9%]; mean body mass index, 32.5 [SD, 6.4]; n=879 [47.2%] women), 1758 (94.3%) completed the trial and 298 prematurely discontinued treatment (16.7% for semaglutide, 3 mg/d; 15.0% for semaglutide, 7 mg/d; 19.1% for semaglutide, 14 mg/d; and 13.1% for sitagliptin). Semaglutide, 7 and 14 mg/d, compared with sitagliptin, significantly reduced HbA(1c) (differences, –0.3% [95% CI, –0.4% to –0.1%] and –0.5% [95% CI, –0.6% to –0.4%], respectively; P
Databáze: OpenAIRE
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