1.
Alirocumab efficacy and safety by body mass index: A pooled analysis from 10 Phase 3 ODYSSEY trials.
Tinahones, FJ, Laufs, U, Cariou, B, Louie, MJ, Yang, J, Thompson, D, Leiter, LA
Diabetes & metabolism. 2020;(4):280-287
Abstract
AIMS: Increased body mass index (BMI) contributes to cardiovascular risk and may influence efficacy of therapeutic antibodies. We investigated the effect of baseline BMI on efficacy and safety of alirocumab, a PCSK9 monoclonal antibody. METHODS In a post-hoc analysis, data were pooled from 10 Phase 3 trials (n=4975) of alirocumab vs. placebo/ezetimibe controls. Alirocumab dose was 150mg every 2 weeks in two trials, and 75mg every 2 weeks with possible increase to 150mg at 12 weeks (based on Week 8 low-density lipoprotein cholesterol [LDL-C]) in eight trials. Efficacy/safety data were assessed in baseline BMI subgroups of≤25,>25 to 30,>30 to 35, and>35kg/m2. RESULTS Baseline LDL-C levels were lower among patients in the higher BMI subgroups. Significant LDL-C reductions from baseline were observed at Weeks 12 and 24 for alirocumab vs. controls, of similar magnitude regardless of baseline BMI (interaction P-value=0.7119). LDL-C<1.81mmol/L (<70mg/dL) was achieved at Week 24 by 69.8-76.4% of alirocumab-treated patients and 9.7-18.4% of control-treated patients, with no pattern by BMI. A greater proportion of patients in higher vs. lower BMI subgroups required alirocumab dose increase (P=0.0343); proportions were 22.5%, 24.9%, 31.7%, and 27.2% of patients across BMI subgroups of≤25,>25 to 30,>30 to 35, and>35kg/m2, respectively. Adverse event frequencies were similar regardless of BMI; injection-site reaction frequency was higher with alirocumab (5.1-8.2% across BMI categories) vs. controls (3.6-4.8%). CONCLUSIONS Alirocumab provided consistent LDL-C reductions, with similar safety findings across BMI subgroups.
2.
Genotype-covariate interaction effects and the heritability of adult body mass index.
Robinson, MR, English, G, Moser, G, Lloyd-Jones, LR, Triplett, MA, Zhu, Z, Nolte, IM, van Vliet-Ostaptchouk, JV, Snieder, H, , , et al
Nature genetics. 2017;(8):1174-1181
Abstract
Obesity is a worldwide epidemic, with major health and economic costs. Here we estimate heritability for body mass index (BMI) in 172,000 sibling pairs and 150,832 unrelated individuals and explore the contribution of genotype-covariate interaction effects at common SNP loci. We find evidence for genotype-age interaction (likelihood ratio test (LRT) = 73.58, degrees of freedom (df) = 1, P = 4.83 × 10-18), which contributed 8.1% (1.4% s.e.) to BMI variation. Across eight self-reported lifestyle factors, including diet and exercise, we find genotype-environment interaction only for smoking behavior (LRT = 19.70, P = 5.03 × 10-5 and LRT = 30.80, P = 1.42 × 10-8), which contributed 4.0% (0.8% s.e.) to BMI variation. Bayesian association analysis suggests that BMI is highly polygenic, with 75% of the SNP heritability attributable to loci that each explain <0.01% of the phenotypic variance. Our findings imply that substantially larger sample sizes across ages and lifestyles are required to understand the full genetic architecture of BMI.
3.
The Effect of Protein-Enriched Meal Replacement on Waist Circumference Reduction among Overweight and Obese Chinese with Hyperlipidemia.
Chen, W, Liu, Y, Yang, Q, Li, X, Yang, J, Wang, J, Shi, L, Chen, Y, Zhu, S
Journal of the American College of Nutrition. 2016;(3):236-44
Abstract
OBJECTIVE In China, high-fat diets and excessive energy intake have led to an increasing prevalence of obesity which was previously uncommon. The current study examined the effects of meal replacement (MR) on weight control in overweight or obese Chinese individuals with hyperlipidemia. METHODS Patients, 18-65 years, with body mass index 25-35 kg/m(2) and triglycerides >1.7 and <5.4 mmol/L were enrolled. Major exclusion criteria were: type II diabetes, fasting glucose ≥7.0 mmol/L, glycosylated hemoglobin ≥6.5%; weight loss surgery or use of weight loss drugs; weight fluctuations >2%; use of cholesterol-lowering drugs. Eligible patients were randomized 1:1 to a high-protein (HP) diet (2.2 g protein/kg/day) or a standard-protein (SP) diet (1.1 g protein/kg/ day) provided twice daily for 3 months. Assessments included body weight, waist-hip ratio, body fat percentage, blood lipids, blood glucose, insulin, liver and kidney function. RESULTS Although mean weight loss and percent BMI reduction were greater with HP than SP at 12 weeks, the differences were not significant. There was, however, a significantly greater decrease in waist-hip ratio with HP versus SP (-0.03 ± 0.03 vs. -0.01 ± 0.04; p < 0.05). Triglycerides decreased from baseline in both groups; however, the difference was not significant. Both HP and SP were well tolerated. This study demonstrated that in obese Chinese patients with hyperlipidemia, a protein-enriched MR diet resulted in significantly reduced waist circumference compared to a standard protein diet. CONCLUSION This first study of protein-enriched partial meal replacement in a free-living Chinese population suggests a new and promising strategy for reducing abdominal obesity in China.