Obesity and GLP-1 RAs

doi:10.1136/jim-2021-002268

Paper

Obesity and GLP-1 RAs

Published Dec 21, 2021 · Tamis Bright

Journal of Investigative Medicine

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Abstract

© American Federation for Medical Research 2021. No commercial reuse. See rights and permissions. Published by BMJ. In this issue of the Journal of Investigative Medicine, Singh et al review the important addition of the glucagonlike peptide1 receptor agonists (GLP1 RAs) for the treatment of obesity and specifically discuss semaglutide for weight management. Despite the dire and costly outcomes of obesity, the USA and much of the world have failed for years to practice healthy eating and exercise. The 2017–2018 National Health and Nutrition Examination Survey (NHANES) estimated that 42.5% of US adults aged 20 and over have obesity and an additional 31.1% are overweight, impacting 73.6% of the adult population. Having excessive weight has now become the “norm” with those overweight or obese far exceeding those of appropriate body weight. As discussed in this review, obesity is of critical concern because it contributes to the development of the top two leading causes of death, heart disease and cancer, as well as a host of other medical conditions such as diabetes and hypertension. For 2020, COVID19 was the third most common cause of death and obesity is a known risk factor for mortality from COVID19 as well. Effective treatments have been lacking. A multitude of diets have come and gone with high dropout rates and very poor longterm weight loss sustainability. A recent metaanalysis with 21,942 patients showed a minimal weight loss of 2.0 kg compared with the usual diet for up to 12 months, with trivial differences between diets. Consequently, treatment with medications and surgical options have now come to the forefront. Usually, surgery is reserved for those with the most excessive obesity due to the invasive nature and side effects, leaving the vast majority of the population with limited medical options to reduce weight. For longterm weight management, orlistat, phentermine/topiramate, and naltrexone/bupropion have been available since 1999, 2012, and 2014, respectively, but have not had widespread use due to cost and concerns over safety and efficacy. The most recent class of medication, the GLP1 RAs, has been a welcome addition to our armamentarium to treat obesity. Initially designed for glucose lowering, recently their indication has been expanded to include weight reduction in nondiabetic populations. There is extensive experience with GLP1 RAs with diabetes and these medications have now become firstline therapies for longterm diabetes treatment not only for their glucose lowering but also due to their improvement in cardiac and renal outcomes. GLP1RAs approved for treatment of obesity without diabetes, liraglutide and now semaglutide, have shown good tolerability with limited side effects, mainly nausea and vomiting, and excellent weight reduction especially in combination with behavioral modification. As noted by the authors, unfortunately GLP1 RAs are currently expensive and not wellcovered by insurance. Weight loss is associated with lower mortality and a decreased risk of diabetes, high blood pressure, hyperlipidemia, cardiovascular disease, and obstructive sleep apnea. Therefore, making these medications more affordable, as well as increasing research to develop additional weight loss medications, is essential.

Study Snapshot

GLP1 RAs, specifically semaglutide, show good tolerability and excellent weight reduction in nondiabetic populations, but their cost and lack of widespread availability hinder their widespread use.

PopulationOlder adults (50-71 years)

Sample size24

MethodsObservational

OutcomesBody Mass Index projections

ResultsSocial networks mitigate obesity in older groups.

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Obesity and GLP-1 RAs

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References

Provisional Mortality Data — United States, 2020

COVID-19 was the third leading cause of death in the United States in 2020, with the highest rates in adults aged 85, non-Hispanic Black and non-Hispanic American Indian or Alaska Native (AI/AN) persons, and males.

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.

Once-weekly subcutaneous semaglutide, 2.4 mg, combined with intensive behavioral therapy and initial low-calorie diet significantly resulted in greater weight loss in adults with overweight or obesity compared to placebo.

Once-Weekly Semaglutide in Adults with Overweight or Obesity.

Once-weekly semaglutide at a dose of 2.4 mg, combined with lifestyle intervention, leads to significant and sustained weight loss in adults with overweight or obesity.

Obesity and Mortality Among Patients Diagnosed With COVID-19: Results From an Integrated Health Care Organization

Obesity is associated with increased mortality 21 days after COVID-19 diagnosis in patients receiving care in an integrated health care system, accounting for obesity-related comorbidities and sociodemographic factors.

Comparison of dietary macronutrient patterns of 14 popular named dietary programmes for weight and cardiovascular risk factor reduction in adults: systematic review and network meta-analysis of randomised trials

Most macronutrient diets lead to modest weight loss and improved cardiovascular risk factors in the first six months, but these effects largely disappear by 12 months.

Citations

Effects of liraglutide on ANP secretion and cardiac dynamics

Liraglutide can decrease atrial natriuretic peptide secretion and atrial pulse pressure in patients with acute coronary syndrome, mediated by GLP-1R and possibly through the PI3K/AKT/mTOR signaling pathway.