Abstract #611: The Impact of Gastrointestinal Adverse Events on Weight loss with Liraglutide 3.0 Mg as Adjunct to a Diet and Exercise Program

The impact of lifestyle-induced weight loss (WL) on appetite in patients with obesity remains controversial. This study aimed to assess the short- and long-term impact of WL achieved by diet and exercise on appetite in patients with obesity. Thirty-five (22 females) adults with severe obesity (body mass index: 42.5 ± 5.0 kg/m2) underwent a 2-yr WL program focusing on diet and exercise. Body weight (BW), cardiovascular fitness (V̇o2max), appetite feelings, and plasma concentrations of insulin, active ghrelin (AG), glucagon-like peptide 1 (GLP-1), peptide YY (PYY), and cholecystokinin (CCK), in the fasting and postprandial states, were measured at baseline (B), week 4 (W4), and 1 and 2 yr (and average values for all fasting and postprandial time points computed). BW was significantly reduced and V̇o2max(ml·kg−1·min−1) increased at all time points compared with B (3.5, 8.1, and 8.4% WL and 7, 11, and 8% increase at W4 and 1 and 2 yr, respectively). Basal hunger and average hunger and desire to eat were significantly increased at 1 and 2 yr. Basal fullness was significantly increased at W4, and average ratings were reduced at 1 yr. Average AG and PYY were significantly increased, and insulin was reduced, at all time points compared with B. Average GLP-1 was reduced at W4, and CCK was increased at 2 yr. After lifestyle-induced WL, patients with severe obesity will, therefore, have to deal with increased hunger in the long term. In conclusion, sustained WL at 2 yr achieved with diet and exercise is associated with increased hunger feelings and ghrelin concentration but also increased postprandial concentrations of satiety hormones.

Download Full-text

Variants in the CHRNA5–CHRNA3–CHRNB4 Region of Chromosome 15 Predict Gastrointestinal Adverse Events in the Transdisciplinary Tobacco Use Research Center Smoking Cessation Trial

Nicotine & Tobacco Research ◽

10.1093/ntr/ntz044 ◽

2019 ◽

Vol 22 (2) ◽

pp. 248-255 ◽

Cited By ~ 1

Author(s):

Robert C Culverhouse ◽

Li-Shiun Chen ◽

Nancy L Saccone ◽

Yinjiao Ma ◽

Megan E Piper ◽

...

Keyword(s):

Smoking Cessation ◽

Adverse Events ◽

Tobacco Use ◽

Genetic Variants ◽

Research Center ◽

European Ancestry ◽

Chromosome 15 ◽

Adherence To Medication ◽

Gastrointestinal Adverse Events ◽

The Impact

Abstract Introduction Reducing adverse events from pharmacologic treatment is an important goal of precision medicine and identifying genetic predictors of adverse events is a step toward this goal. In 2012, King et al. reported associations between genetic variants and adverse events in a placebo-controlled smoking cessation trial of varenicline and bupropion. Strong associations were found between gastrointestinal adverse events and 11 variants in the CHRNA5–CHRNA3–CHRNB4 region of chromosome 15, a region repeatedly associated with smoking-related phenotypes. Our goal was to replicate, in an independent sample, the impact of variants in the CHRNA5–CHRNA3–CHRNB4 region on gastrointestinal adverse events and to extend the analyses to adherence and smoking cessation. Methods The University of Wisconsin Transdisciplinary Tobacco Use Research Center (TTURC) conducted a multiarmed, placebo-controlled smoking cessation trial of bupropion and nicotine replacement therapy that included 985 genotyped European-ancestry participants. We evaluated relationships between our key variables using logistic regression. Results Gastrointestinal adverse events were experienced by 31.6% TTURC participants. Each of the CHRNA5–CHRNA3–CHRNB4 associations from the King et al. study was found in TTURC, with the same direction of effect. Neither these variants nor the gastrointestinal adverse events themselves were associated with adherence to medication or successful smoking cessation. Conclusions Variants in the CHRNA5–CHRNA3–CHRNB4 region of chromosome 15 are associated with gastrointestinal adverse events in smoking cessation. Additional independent variants in this region strengthen the association. The consistency between the results of these two independent studies supports the conclusion that these findings reflect biological response to the use of smoking cessation medication. Implications The fact that our findings from the TTURC smoking cessation trial support the independent findings of King et al. suggest that associations of variants in the CHRNA5–CHRNA3–CHRNB4 region of chromosome 15 with gastrointestinal adverse events while taking medications for smoking cessation reflect biology. However, although adherence to medication was a strong predictor of successful smoking cessation in TTURC, neither adverse events nor the genetic variants associated with them predicted either adherence or successful cessation in this study. Thus, although we should strive to minimize adverse events during treatment, we should not expect that to increase successful smoking cessation substantially.

Download Full-text

Impact of Diet and/or Exercise Intervention on Infrapatellar Fat Pad Morphology: Secondary Analysis from the Intensive Diet and Exercise for Arthritis (IDEA) Trial

Cells Tissues Organs ◽

10.1159/000449407 ◽

2017 ◽

Vol 203 (4) ◽

pp. 258-266 ◽

Cited By ~ 11

Author(s):

Aarón Leonardo Pogacnik Murillo ◽

Felix Eckstein ◽

Wolfgang Wirth ◽

Daniel Beavers ◽

Richard F. Loeser ◽

...

Keyword(s):

Weight Loss ◽

Body Fat ◽

Secondary Analysis ◽

Magnetic Resonance Images ◽

Infrapatellar Fat Pad ◽

Average Weight ◽

Fat Pad ◽

Exercise Interventions ◽

Diet And Exercise ◽

The Impact

Objectives: The infrapatellar fat pad (IPFP) represents intra-articular adipose tissue that may contribute to intra-articular inflammation and pain by secretion of proinflammatory cytokines. Here we examined the impact of weight loss by diet and/or exercise interventions on the IPFP volume. Methods: Intensive Diet and Exercise for Arthritis (IDEA) was a single-blinded, single-center, 18-month, prospective, randomized controlled trial that enrolled 454 overweight and obese older adults with knee pain and radiographic osteoarthritis. Participants were randomized to 1 of 3 groups: exercise-only control (E), diet-induced weight loss (D), and diet-induced weight loss + exercise (D+E). In a subsample (n = 106; E: n = 36, D: n = 35, and D+E: n = 35), magnetic resonance images were acquired at baseline and at the 18-month follow-up, from which we analyzed IPFP volume, surface areas, and thickness in this secondary analysis. Results: The average weight loss amounted to 1.0% in the E group, 10.5% in the D group, and 13.0% in the D+E group. A significant (p < 0.01) reduction in IPFP volume was observed in the E (2.1%), D (4.0%), and D+E (5.2%) groups. The IPFP volume loss in the D+E group was significantly greater than that in the E group (p < 0.05) when not adjusting for parallel comparisons. Across intervention groups, there were significant correlations between IPFP volume change, individual weight loss (r = 0.40), and change in total body fat mass (dual-energy X-ray absorptiometry; r = 0.44, n = 88) and in subcutaneous thigh fat area (computed tomography; r = 0.32, n = 82). Conclusions: As a potential link between obesity and knee osteoarthritis, the IPFP was sensitive to intervention by diet and/or exercise, and its reduction was correlated with changes in weight and body fat.

Download Full-text

A Structured Diet and Exercise Program Promotes Favorable Changes in Weight Loss, Body Composition, and Weight Maintenance

Journal of the American Dietetic Association ◽

10.1016/j.jada.2011.03.013 ◽

2011 ◽

Vol 111 (6) ◽

pp. 828-843 ◽

Cited By ~ 23

Author(s):

Richard B. Kreider ◽

Monica Serra ◽

Kristen M. Beavers ◽

Jen Moreillon ◽

Julie Y. Kresta ◽

...

Keyword(s):

Weight Loss ◽

Body Composition ◽

Weight Maintenance ◽

Exercise Program ◽

Diet And Exercise

Download Full-text

Weight Loss Maintenance With Once-Weekly Semaglutide 2.4 MG in Adults With Overweight or Obesity Reaching Maintenance Dose (STEP 4)

Journal of the Endocrine Society ◽

10.1210/jendso/bvab048.129 ◽

2021 ◽

Vol 5 (Supplement_1) ◽

pp. A63-A64

Author(s):

Domenica M Rubino ◽

Niclas Abrahamsson ◽

Melanie Davies ◽

Dan Hesse ◽

Frank L Greenway ◽

...

Keyword(s):

Blood Pressure ◽

Weight Loss ◽

Body Weight ◽

Waist Circumference ◽

Adverse Events ◽

Systolic Blood Pressure ◽

Maintenance Dose ◽

Treatment Policy ◽

The Impact ◽

Overweight Or Obesity

Abstract Background: In people with overweight or obesity, long-term maintenance of weight loss is challenging. Subcutaneous (s.c.) semaglutide, a glucagon-like peptide-1 analogue, has shown clinically-relevant weight loss in a phase 2 trial in people with obesity. STEP 4 investigated the impact of continued semaglutide 2.4 mg treatment, vs switching to placebo, on maintenance of weight loss in participants who reached 2.4 mg of semaglutide during a run-in period. Methods: This was a 68-week withdrawal trial (NCT03548987) in 902 subjects aged ≥18 years with body mass index (BMI) ≥30 kg/m2 (or BMI ≥27 kg/m2 with ≥1 weight-related comorbidity), without diabetes. Following a 20 week run-in period, 803 subjects who reached the maintenance dose of once-weekly (OW) s.c. semaglutide 2.4 mg were randomized 2:1 to continue treatment with semaglutide 2.4 mg or switch to placebo for 48 weeks, both as adjunct to lifestyle intervention. The primary endpoint was percentage change in body weight between randomization (week 20) and week 68. Confirmatory secondary endpoints included change in waist circumference and systolic blood pressure. Two estimands were defined: treatment policy and trial product; results are presented for the treatment policy estimand, unless stated otherwise. Results: Mean body weight (±SD) was 107.2 ±22.7 kg at week 0 and 96.1 ±22.6 kg at randomization (week 20; mean change -10.6%). Randomized participants were mostly female (79%) and white (84%); mean age was 46 years and mean BMI was 34.4 kg/m2. Between weeks 20–68, estimated mean body weight change was −7.9% vs +6.9% for semaglutide 2.4 mg vs placebo (estimated treatment difference [ETD]: −14.8%; 95% confidence interval [CI]: −16.0, −13.5; p<0.0001), and -8.8% vs 6.5%, respectively, for the trial product estimand (ETD: -15.3%; 95% CI: -16.5, -14.1; p<0.0001). For participants randomized to continue semaglutide, the estimated change in body weight from week 0–68 was -17.4% (-18.2% for trial product estimand). Continued semaglutide treatment (weeks 20–68) led to clinically-relevant improvements in waist circumference, systolic blood pressure, BMI, HbA1c, FPG, and lipids (total cholesterol, LDL, VLDL, and triglycerides) vs switching to placebo (p<0.0001 for all). During the run-in period, 5.3% of participants discontinued treatment due to adverse events; during the randomized period, 2.4% (semaglutide) and 2.2% (placebo) discontinued. Nausea, diarrhea and constipation (mostly transient and mild-to-moderate) were the most frequent adverse events with semaglutide. Conclusion: In adults with overweight or obesity, continued treatment after dose escalation with OW s.c. semaglutide 2.4 mg until week 68 led to clinically-relevant weight loss, while switching to placebo led to significant weight regain; these data underscore the chronicity and relapsing nature of obesity, and the need for continued treatment.

Download Full-text