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Approach to Obesity Treatment in Primary Care: A Review

Author/s: 
Susan Z Yanovski, Jack A Yanovski

Importance: More than 40% of US adults have obesity, which increases the risks for multiple chronic diseases and premature mortality. Historically, nonsurgical interventions often have not led to sufficient weight loss and maintenance to improve health, but highly effective antiobesity medications (AOMs) have recently become available, and additional effective therapeutics are under development. Given that most medical care for adults with obesity is delivered in primary care settings, guidance for integrating weight-management approaches is needed.

Observations: Lifestyle interventions can lead to a mean weight loss of 2% to 9% of initial weight at 1 year and increase the likelihood of weight loss of 5% or more, but weight regain over time is common even with continued treatment. Adjunctive treatments, including AOMs and surgical approaches, can lead to larger, more sustained weight loss and improvements in numerous obesity-associated medical conditions. Highly effective AOMs, including nutrient-stimulated hormone-based therapies, induce mean weight loss of 15% or more. Barriers to intervention, including access to care, have a disproportionate influence on populations most affected by obesity and its consequences.

Conclusions and relevance: Primary care clinicians play a vital role in the assessment, management, and support of patients with obesity. With careful clinical assessment and shared decision-making, a flexible treatment plan can be developed that reflects evidence of treatment efficacy, patient preference, and feasibility of implementation. Adjunctive therapies to lifestyle interventions, including more effective pharmacotherapeutics for obesity, offer hope to patients and the potential for considerable improvements in health and quality of life.

Keywords 
obesity lifestyle behaviors diet weight loss weight gain body weight

Risk of Gastrointestinal Adverse Events Associated With Glucagon-Like Peptide-1 Receptor Agonists for Weight Loss

Author/s: 
Mohit Sodhi, Ramin Rezaeianzadeh, Abbas Kezouh, Mahyar Etminan

This database study examines the association between glucagon-like peptide 1 agonists (eg, semaglutide, liraglutide) used for weight loss and reports of gastrointestinal adverse events.

Keywords 
weight loss body weight obesity diabetes Gastroenterology

Effects of Tai Chi or Conventional Exercise on Central Obesity in Middle-Aged and Older Adults : A Three-Group Randomized Controlled Trial

Author/s: 
Siu, P. M., Yu, A. P., Chin, E. C., Yu, D. S., Hui, S. S., Woo, J., Fong, D. Y., Wei, G. X., Irwin, M. R.

Background: Central obesity is a major manifestation of metabolic syndrome, which is a common health problem in middle-aged and older adults.

Objective: To examine the therapeutic efficacy of tai chi for management of central obesity.

Design: Randomized, controlled, assessor-blinded trial. (ClinicalTrials.gov: NCT03107741).

Setting: A single research site in Hong Kong between 27 February 2016 and 28 February 2019.

Participants: Adults aged 50 years or older with central obesity.

Intervention: 543 participants were randomly assigned in a 1:1:1 ratio to a control group with no exercise intervention (n = 181), conventional exercise consisting of aerobic exercise and strength training (EX group) (n = 181), and a tai chi group (TC group) (n = 181). Interventions lasted 12 weeks.

Measurements: Outcomes were assessed at baseline, week 12, and week 38. The primary outcome was waist circumference (WC). Secondary outcomes were body weight; body mass index; high-density lipoprotein cholesterol (HDL-C), triglyceride, and fasting plasma glucose levels; blood pressure; and incidence of remission of central obesity.

Results: The adjusted mean difference in WC from baseline to week 12 in the control group was 0.8 cm (95% CI, -4.1 to 5.7 cm). Both intervention groups showed reductions in WC relative to control (adjusted mean differences: TC group vs. control, -1.8 cm [CI, -2.3 to -1.4 cm]; P < 0.001; EX group vs. control: -1.3 cm [CI, -1.8 to -0.9 cm]; P < 0.001); both intervention groups also showed reductions in body weight (P < 0.05) and attenuation of the decrease in HDL-C level relative to the control group. The favorable changes in WC and body weight were maintained in both the TC and EX groups, whereas the beneficial effect on HDL-C was only maintained in the TC group at week 38.

Limitations: High attrition and no dietary intervention.

Conclusion: Tai chi is an effective approach to reduce WC in adults with central obesity aged 50 years or older.

Primary funding source: Health and Medical Research Fund.

Keywords 
Tai Chi conventional exercise obesity results Adults trial

Association of metabolic–bariatric surgery with long-term survival in adults with and without diabetes: a one-stage meta-analysis of matched cohort and prospective controlled studies with 174772 participants

Author/s: 
Syn, N.L, Cummings, D. E., Wang, L. Z., Lin, D. J., Zhao, J. J., Loh, M., Koh, Z. J., Chew, C. A., Kim, G., Bok-Yan So, J., Kaplan, L. M., Dixon, J. B., Shabbir, A.

Summary Background Metabolic–bariatric surgery delivers substantial weight loss and can induce remission or improvement of obesity-related risks and complications. However, more robust estimates of its effect on long-term mortality and life expectancy—especially stratified by pre-existing diabetes status—are needed to guide policy and facilitate patient counselling. We compared long-term survival outcomes of severely obese patients who received metabolic–bariatric surgery versus usual care. Methods We did a prespecified one-stage meta-analysis using patient-level survival data reconstructed from prospective controlled trials and high-quality matched cohort studies. We searched PubMed, Scopus, and MEDLINE (via Ovid) for randomised trials, prospective controlled studies, and matched cohort studies comparing all-cause mortality after metabolic–bariatric surgery versus non-surgical management of obesity published between inception and Feb 3, 2021. We also searched grey literature by reviewing bibliographies of included studies as well as review articles. Shared-frailty (ie, random-effects) and stratified Cox models were fitted to compare all-cause mortality of adults with obesity who underwent metabolic–bariatric surgery compared with matched controls who received usual care, taking into account clustering of participants at the study level. We also computed numbers needed to treat, and extrapolated life expectancy using Gompertz proportional-hazards modelling. The study protocol is prospectively registered on PROSPERO, number CRD42020218472. 

Keywords 
gastric bypass obesity proportional hazard models bariatric surgery gastrectomy weight loss

Once-Weekly Semaglutide in Adults with Overweight or Obesity

Author/s: 
Wilding, John P.H., Batterham, Rachel L., Calanna, Salvatore, Davies, Melanie, Van Gaal, Luc F., Lingvay, Ildiko, McGowan, Barbara M., Rosenstock, Julio, Tran, Marie T.D., Wadden, Thomas A.,, Sean, Yokote, Koutaro, Zeuthen, Niels, Kushner, Robert F., STEP 1 Study Group

Background: Obesity is a global health challenge with few pharmacologic options. Whether adults with obesity can achieve weight loss with once-weekly semaglutide at a dose of 2.4 mg as an adjunct to lifestyle intervention has not been confirmed.

Methods: In this double-blind trial, we enrolled 1961 adults with a body-mass index (the weight in kilograms divided by the square of the height in meters) of 30 or greater (≥27 in persons with ≥1 weight-related coexisting condition), who did not have diabetes, and randomly assigned them, in a 2:1 ratio, to 68 weeks of treatment with once-weekly subcutaneous semaglutide (at a dose of 2.4 mg) or placebo, plus lifestyle intervention. The coprimary end points were the percentage change in body weight and weight reduction of at least 5%. The primary estimand (a precise description of the treatment effect reflecting the objective of the clinical trial) assessed effects regardless of treatment discontinuation or rescue interventions.

Results: The mean change in body weight from baseline to week 68 was -14.9% in the semaglutide group as compared with -2.4% with placebo, for an estimated treatment difference of -12.4 percentage points (95% confidence interval [CI], -13.4 to -11.5; P<0.001). More participants in the semaglutide group than in the placebo group achieved weight reductions of 5% or more (1047 participants [86.4%] vs. 182 [31.5%]), 10% or more (838 [69.1%] vs. 69 [12.0%]), and 15% or more (612 [50.5%] vs. 28 [4.9%]) at week 68 (P<0.001 for all three comparisons of odds). The change in body weight from baseline to week 68 was -15.3 kg in the semaglutide group as compared with -2.6 kg in the placebo group (estimated treatment difference, -12.7 kg; 95% CI, -13.7 to -11.7). Participants who received semaglutide had a greater improvement with respect to cardiometabolic risk factors and a greater increase in participant-reported physical functioning from baseline than those who received placebo. Nausea and diarrhea were the most common adverse events with semaglutide; they were typically transient and mild-to-moderate in severity and subsided with time. More participants in the semaglutide group than in the placebo group discontinued treatment owing to gastrointestinal events (59 [4.5%] vs. 5 [0.8%]).

Conclusions: In participants with overweight or obesity, 2.4 mg of semaglutide once weekly plus lifestyle intervention was associated with sustained, clinically relevant reduction in body weight. (Funded by Novo Nordisk; STEP 1 ClinicalTrials.gov number, NCT03548935).

Keywords 
obesity Global Health overweight Semaglutide weight loss Life Style

Effect of Subcutaneous Semaglutide vs Placebo as an Adjunct to Intensive Behavioral Therapy on Body Weight in Adults With Overweight or Obesity: The STEP 3 Randomized Clinical Trial

Author/s: 
Wadden, Thomas A., Bailey, Timothy S., Billings, Liana K., Davies, Melanie, Frias, Juan P., Koroleva, Anna, Lingvay, Ildiko, O'Neil, Patrick M., Runino, Domenica M., Skovgaard, Dorthe, Wallenstein, Signe O.R., Garvey, W. TImothy, STEP 3 Investigators

Importance: Weight loss improves cardiometabolic risk factors in people with overweight or obesity. Intensive lifestyle intervention and pharmacotherapy are the most effective noninvasive weight loss approaches.

Objective: To compare the effects of once-weekly subcutaneous semaglutide, 2.4 mg vs placebo for weight management as an adjunct to intensive behavioral therapy with initial low-calorie diet in adults with overweight or obesity.

Design, setting, and participants: Randomized, double-blind, parallel-group, 68-week, phase 3a study (STEP 3) conducted at 41 sites in the US from August 2018 to April 2020 in adults without diabetes (N = 611) and with either overweight (body mass index ≥27) plus at least 1 comorbidity or obesity (body mass index ≥30).

Interventions: Participants were randomized (2:1) to semaglutide, 2.4 mg (n = 407) or placebo (n = 204), both combined with a low-calorie diet for the first 8 weeks and intensive behavioral therapy (ie, 30 counseling visits) during 68 weeks.

Main outcomes and measures: The co-primary end points were percentage change in body weight and the loss of 5% or more of baseline weight by week 68. Confirmatory secondary end points included losses of at least 10% or 15% of baseline weight.

Results: Of 611 randomized participants (495 women [81.0%], mean age 46 years [SD, 13], body weight 105.8 kg [SD, 22.9], and body mass index 38.0 [SD, 6.7]), 567 (92.8%) completed the trial, and 505 (82.7%) were receiving treatment at trial end. At week 68, the estimated mean body weight change from baseline was -16.0% for semaglutide vs -5.7% for placebo (difference, -10.3 percentage points [95% CI, -12.0 to -8.6]; P < .001). More participants treated with semaglutide vs placebo lost at least 5% of baseline body weight (86.6% vs 47.6%, respectively; P < .001). A higher proportion of participants in the semaglutide vs placebo group achieved weight losses of at least 10% or 15% (75.3% vs 27.0% and 55.8% vs 13.2%, respectively; P < .001). Gastrointestinal adverse events were more frequent with semaglutide (82.8%) vs placebo (63.2%). Treatment was discontinued owing to these events in 3.4% of semaglutide participants vs 0% of placebo participants.

Conclusions and relevance: Among adults with overweight or obesity, once-weekly subcutaneous semaglutide compared with placebo, used as an adjunct to intensive behavioral therapy and initial low-calorie diet, resulted in significantly greater weight loss during 68 weeks. Further research is needed to assess the durability of these findings.

Keywords 
weight loss body mass index BMI body weight obesity

Obesity in adults: a clinical practice guideline

Author/s: 
Wharton, Sean, Lau, David C., Vallis, Mchael, Sharma, Arya M., Biertho, Laurent, Campbell-Scherer, Denise, Adamo, Kristi, Alberga, Anela, Bell, Rhonda, Boule, Normand, Boyling, Elaine, Calam, Betty, Brown, Jennifer, Clarke, Carol, Crowshoe, Lindsay", Mary, Freedhoff, Yoni, Gagner, Michel, Grand, Cindy, Glazer, Stephen", Michael, Hahn, Margaret, Hawa, Raed, Henderson, Rita, Hong, Dennis, Hung, Pam, Janssen, Ian, Jacklin, Kristen, Johnson-Stoklossa, Carlene, Kemp, Amy, Kirk, Sra, :Kuk, Jennifer, Langlois, Marie-France, Lear, Scott, McInnes, Ashley, Macklin, David, Naji, Leen, Manjoo, Priya, Morin, Marie-Philippe, Nerenberg, Kara, Patton, Ian, Pedersen, Sue, Pereira, Leticia, Piccinini-Vallis, Helena, Poddar, Megha, Poirier, Paul, Prud'homme, Denis, Romos Salas, Ximena, Rueda-Clausen, Christian, Russell-Mayhew, Shelly, Shiau, Judy, Sherifali, Diana, Sievenpiper, John, Sockalingam, Sanjeev, Taylor, Valerie, Toth, Ellen, Twells, Laurie, Tytus, RIchard, Walji, Shahebina, Walker, Leah

  • Obesity is a prevalent, complex, progressive and relapsing chronic disease, characterized by abnormal or excessive body fat (adiposity), that impairs health.

  • People living with obesity face substantial bias and stigma, which contribute to increased morbidity and mortality independent of weight or body mass index.

  • This guideline update reflects substantial advances in the epidemiology, determinants, pathophysiology, assessment, prevention and treatment of obesity, and shifts the focus of obesity management toward improving patient-centred health outcomes, rather than weight loss alone.

  • Obesity care should be based on evidence-based principles of chronic disease management, must validate patients’ lived experiences, move beyond simplistic approaches of “eat less, move more,” and address the root drivers of obesity.

  • People living with obesity should have access to evidence-informed interventions, including medical nutrition therapy, physical activity, psychological interventions, pharmacotherapy and surgery.

Keywords 
obesity Stigmas diabetes, type 2 diabetes Gallbladder disease non-alcoholic fatty liver disease Gout

Life Expectancy after Bariatric Surgery in the Swedish Obese Subjects Study

Author/s: 
Carlsson, Lena M.S., Sjöholm, Kajsa, Jacobson, Peter, Andersson-Assarsson, Johanna C., Svensson, Per-Arne, Taube, Magdalena, Carlsson, Björn, Peltonen, Markku

BACKGROUND

Obesity shortens life expectancy. Bariatric surgery is known to reduce the long-term relative risk of death, but its effect on life expectancy is unclear.

METHODS

We used the Gompertz proportional hazards regression model to compare mortality and life expectancy among patients treated with either bariatric surgery (surgery group) or usual obesity care (control group) in the prospective, controlled Swedish Obese Subjects (SOS) study and participants in the SOS reference study (reference cohort), a random sample from the general population.

RESULTS

In total, 2007 and 2040 patients were included in the surgery group and the control group, respectively, and 1135 participants were included in the reference cohort. At the time of the analysis (December 31, 2018), the median duration of follow-up for mortality was 24 years (interquartile range, 22 to 27) in the surgery group and 22 years (interquartile range, 21 to 27) in the control group; data on mortality were available for 99.9% of patients in the study. In the SOS reference cohort, the median duration of follow-up was 20 years (interquartile range, 19 to 21), and data on mortality were available for 100% of participants. In total, 457 patients (22.8%) in the surgery group and 539 patients (26.4%) in the control group died (hazard ratio, 0.77; 95% confidence interval [CI], 0.68 to 0.87; P<0.001). The corresponding hazard ratio was 0.70 (95% CI, 0.57 to 0.85) for death from cardiovascular disease and 0.77 (95% CI, 0.61 to 0.96) for death from cancer. The adjusted median life expectancy in the surgery group was 3.0 years (95% CI, 1.8 to 4.2) longer than in the control group but 5.5 years shorter than in the general population. The 90-day postoperative mortality was 0.2%, and 2.9% of the patients in the surgery group underwent repeat surgery.

CONCLUSIONS

Among patients with obesity, bariatric surgery was associated with longer life expectancy than usual obesity care. Mortality remained higher in both groups than in the general population. 

Keywords 
Life expectancy obesity bariatric surgery

A Randomized, Controlled Trial of Liraglutide for Adolescents With Obesity

Author/s: 
Kelly, AS, Auerbach, P, Barrientos-Perez, M, Gies, I, Hale, PM, Marcus, C, Mastrandrea, LD, Prabhu, N, Arslanian, S, NN8022-4180 Trial Investigators

Background: Obesity is a chronic disease with limited treatment options in pediatric patients. Liraglutide may be useful for weight management in adolescents with obesity.

Methods: In this randomized, double-blind trial, which consisted of a 56-week treatment period and a 26-week follow-up period, we enrolled adolescents (12 to <18 years of age) with obesity and a poor response to lifestyle therapy alone. Participants were randomly assigned (1:1) to receive either liraglutide (3.0 mg) or placebo subcutaneously once daily, in addition to lifestyle therapy. The primary end point was the change from baseline in the body-mass index (BMI; the weight in kilograms divided by the square of the height in meters) standard-deviation score at week 56.

Results: A total of 125 participants were assigned to the liraglutide group and 126 to the placebo group. Liraglutide was superior to placebo with regard to the change from baseline in the BMI standard-deviation score at week 56 (estimated difference, -0.22; 95% confidence interval [CI], -0.37 to -0.08; P = 0.002). A reduction in BMI of at least 5% was observed in 51 of 113 participants in the liraglutide group and in 20 of 105 participants in the placebo group (estimated percentage, 43.3% vs. 18.7%), and a reduction in BMI of at least 10% was observed in 33 and 9, respectively (estimated percentage, 26.1% vs. 8.1%). A greater reduction was observed with liraglutide than with placebo for BMI (estimated difference, -4.64 percentage points) and for body weight (estimated difference, -4.50 kg [for absolute change] and -5.01 percentage points [for relative change]). After discontinuation, a greater increase in the BMI standard-deviation score was observed with liraglutide than with placebo (estimated difference, 0.15; 95% CI, 0.07 to 0.23). More participants in the liraglutide group than in the placebo group had gastrointestinal adverse events (81 of 125 [64.8%] vs. 46 of 126 [36.5%]) and adverse events that led to discontinuation of the trial treatment (13 [10.4%] vs. 0). Few participants in either group had serious adverse events (3 [2.4%] vs. 5 [4.0%]). One suicide, which occurred in the liraglutide group, was assessed by the investigator as unlikely to be related to the trial treatment.

Conclusions: In adolescents with obesity, the use of liraglutide (3.0 mg) plus lifestyle therapy led to a significantly greater reduction in the BMI standard-deviation score than placebo plus lifestyle therapy. (Funded by Novo Nordisk; NN8022-4180 ClinicalTrials.gov number, NCT02918279.).

Keywords 
obesity children adolscent body mass index body weight weight loss
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