Exposure-response analyses of liraglutide 3.0 mg for weight management

Autor: Rune Viig Overgaard, Lisbeth V. Jacobsen, Christine B. Jensen, John P.H. Wilding, C. W. le Roux
Rok vydání: 2016
Předmět:
Male
Endocrinology
Diabetes and Metabolism
Type 2 diabetes
Gastroenterology
Body Mass Index
Cohort Studies
0302 clinical medicine
Endocrinology
Weight loss
Weight management
030212 general & internal medicine
pharmacokinetic
Sex Characteristics
education.field_of_study
Middle Aged
Combined Modality Therapy
incretin
Tolerability
Original Article
Female
medicine.symptom
medicine.drug
medicine.medical_specialty
Diet
Reducing
Population
030209 endocrinology & metabolism
Incretins
Glucagon-Like Peptide-1 Receptor
Prediabetic State
body weight
03 medical and health sciences
Double-Blind Method
Diabetes mellitus
Internal medicine
Appetite Depressants
Weight Loss
Internal Medicine
medicine
Humans
Hypoglycemic Agents
Obesity
education
Adverse effect
Exercise
Dose-Response Relationship
Drug
glucagon‐like peptide‐1
Liraglutide
business.industry
Original Articles
Overweight
medicine.disease
Diabetes Mellitus
Type 2
business
Zdroj: Diabetes, Obesity & Metabolism
ISSN: 1462-8902
DOI: 10.1111/dom.12639
Popis: Aims Liraglutide 3.0 mg, an acylated GLP-1 analogue approved for weight management, lowers body weight through decreased energy intake. We conducted exposure-response analyses to provide important information on individual responses to given drug doses, reflecting inter-individual variations in drug metabolism, absorption and excretion. Methods We report efficacy and safety responses across a wide range of exposure levels, using data from one phase II (liraglutide doses 1.2, 1.8, 2.4 and 3.0 mg), and two phase IIIa [SCALE Obesity and Prediabetes (3.0 mg); SCALE Diabetes (1.8; 3.0 mg)] randomized, placebo-controlled trials (n = 4372). Results There was a clear exposure–weight loss response. Weight loss increased with greater exposure and appeared to level off at the highest exposures associated with liraglutide 3.0 mg in most individuals, but did not fully plateau in men. In individuals with overweight/obesity and comorbid type 2 diabetes, there was a clear exposure–glycated haemoglobin (HbA1c) relationship. HbA1c reduction increased with higher plasma liraglutide concentration (plateauing at ∼21 nM); however, for individuals with baseline HbA1c >8.5%, HbA1c reduction did not fully plateau. No exposure–response relationship was identified for any safety outcome, with the exception of gastrointestinal adverse events (AEs). Individuals with gallbladder AEs, acute pancreatitis or malignant/breast/benign colorectal neoplasms did not have higher liraglutide exposure compared with the overall population. Conclusions These analyses support the use of liraglutide 3.0 mg for weight management in all subgroups investigated; weight loss increased with higher drug exposure, with no concomitant deterioration in safety/tolerability besides previously known gastrointestinal side effects.
Databáze: OpenAIRE
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