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.
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.
- 2019
Available online from MWHC library: 1995 - present, Available in print through MWHC library: 1999 - 2006
CONCLUSIONS: Oral semaglutide was superior to placebo in reducing HbA1c and body weight when added to insulin +/- metformin in patients with type 2 diabetes. The safety profile was consistent with other glucagon-like peptide-1 receptor agonists. Copyright (c) 2019 by the American Diabetes Association. OBJECTIVE: To investigate the efficacy, safety and tolerability of oral semaglutide added to insulin +/- metformin. RESEARCH DESIGN AND METHODS: Patients with type 2 diabetes uncontrolled on insulin, +/- metformin, were randomized to oral semaglutide 3 mg (N=184), 7 mg (N=182), or 14 mg (N=181), or placebo (N=184) in a 52-week, double-blind trial (NCT03021187). Endpoints were change from baseline to week 26 in HbA1c (primary) and body weight (confirmatory secondary). Two estimands were defined: treatment policy (effect regardless of trial product discontinuation or rescue medication) and trial product (effect assuming trial product continuation without rescue medication) in randomized patients. RESULTS: Oral semaglutide was superior to placebo in reducing HbA1c (estimated treatment differences [ETD] [95% CI]: -0.5% [-0.7, -0.3], -0.9% [-1.1, -0.7], -1.2% [-1.4, -1.0] for 3, 7, and 14 mg, respectively; P<0.001) and body weight (ETD [95% CI]: -0.9 kg [-1.8, -0.0], -2.0 kg [-3.0, -1.0], -3.3 kg [-4.2, -2.3]; P=0.0392 for 3 mg, P<=0.0001 for 7 and 14 mg) at week 26 (treatment policy estimand). Significantly greater, dose-dependent HbA1c, and body weight reductions versus placebo were achieved with oral semaglutide at weeks 26 and 52 (both estimands). The most frequent adverse event with oral semaglutide was nausea (11.4-23.2% of patients vs 7.1% with placebo; mostly mild-to-moderate).
English
0149-5992
10.2337/dc19-0898 [doi] dc19-0898 [pii]
*Diabetes Mellitus, Type 2/dt [Drug Therapy]
*Glucagon-Like Peptides/ad [Administration & Dosage]
*Hypoglycemic Agents/ad [Administration & Dosage]
*Insulin/ad [Administration & Dosage]
*Metformin/ad [Administration & Dosage]
Adult
Body Weight/de [Drug Effects]
Diabetes Mellitus, Type 2/bl [Blood]
Double-Blind Method
Drug Therapy, Combination
Female
Glycated Hemoglobin A/de [Drug Effects]
Humans
Male
Middle Aged
Nausea/ci [Chemically Induced]
Treatment Outcome
Weight Loss/de [Drug Effects]
MedStar Health Research Institute
Journal Article
Available online from MWHC library: 1995 - present, Available in print through MWHC library: 1999 - 2006
CONCLUSIONS: Oral semaglutide was superior to placebo in reducing HbA1c and body weight when added to insulin +/- metformin in patients with type 2 diabetes. The safety profile was consistent with other glucagon-like peptide-1 receptor agonists. Copyright (c) 2019 by the American Diabetes Association. OBJECTIVE: To investigate the efficacy, safety and tolerability of oral semaglutide added to insulin +/- metformin. RESEARCH DESIGN AND METHODS: Patients with type 2 diabetes uncontrolled on insulin, +/- metformin, were randomized to oral semaglutide 3 mg (N=184), 7 mg (N=182), or 14 mg (N=181), or placebo (N=184) in a 52-week, double-blind trial (NCT03021187). Endpoints were change from baseline to week 26 in HbA1c (primary) and body weight (confirmatory secondary). Two estimands were defined: treatment policy (effect regardless of trial product discontinuation or rescue medication) and trial product (effect assuming trial product continuation without rescue medication) in randomized patients. RESULTS: Oral semaglutide was superior to placebo in reducing HbA1c (estimated treatment differences [ETD] [95% CI]: -0.5% [-0.7, -0.3], -0.9% [-1.1, -0.7], -1.2% [-1.4, -1.0] for 3, 7, and 14 mg, respectively; P<0.001) and body weight (ETD [95% CI]: -0.9 kg [-1.8, -0.0], -2.0 kg [-3.0, -1.0], -3.3 kg [-4.2, -2.3]; P=0.0392 for 3 mg, P<=0.0001 for 7 and 14 mg) at week 26 (treatment policy estimand). Significantly greater, dose-dependent HbA1c, and body weight reductions versus placebo were achieved with oral semaglutide at weeks 26 and 52 (both estimands). The most frequent adverse event with oral semaglutide was nausea (11.4-23.2% of patients vs 7.1% with placebo; mostly mild-to-moderate).
English
0149-5992
10.2337/dc19-0898 [doi] dc19-0898 [pii]
*Diabetes Mellitus, Type 2/dt [Drug Therapy]
*Glucagon-Like Peptides/ad [Administration & Dosage]
*Hypoglycemic Agents/ad [Administration & Dosage]
*Insulin/ad [Administration & Dosage]
*Metformin/ad [Administration & Dosage]
Adult
Body Weight/de [Drug Effects]
Diabetes Mellitus, Type 2/bl [Blood]
Double-Blind Method
Drug Therapy, Combination
Female
Glycated Hemoglobin A/de [Drug Effects]
Humans
Male
Middle Aged
Nausea/ci [Chemically Induced]
Treatment Outcome
Weight Loss/de [Drug Effects]
MedStar Health Research Institute
Journal Article