The authors used data from 3663 population-based studies with 222 million participants that measured height and weight in representative samples of the general population.
Key findings:
More than a billion people globally are now considered obese.
Obesity has more than quadrupled among children and adolescents since 1990.
Among all adults, 43 percent were overweight in 2022.
The combined burden of underweight and obesity has increased in most countries, driven by an increase in obesity, while underweight and thinness remain prevalent in south Asia and parts of Africa.
The trend of increasing obesity prevalence was present in adults and children (5-19 years).
Age-standardized prevalence of obesity increased by more than 20 percentage points in 49 countries (25%) for women and 24 countries (12%) for men, and by as much as 33·0 percentage points in The Bahamas for women and 31·7 percentage points in Romania for men.
My take: This is an impressive study providing extensive data on what’s happening with weight trends. Clearly, there is an urgent need for obesity prevention.
Methods: This retrospective cohort study analyzed electronic health record data of 603,051 adolescents aged 13 to 17 years between January 1, 2018, and December 31, 2021
Key findings:
4.4% (1 in 23) of all adolescents met the eligibility criteria for bariatric surgery.
22.2% had obesity (12.9% class 1, 5.4% class 2, and 3.9% class 3).
The most frequently diagnosed comorbid conditions were gastroesophageal reflux disease (3.2%), hypertension (0.5%), and nonalcoholic fatty liver disease (0.5%).
The authors estimate that ~1 million U.S. adolescents meet criteria for bariatric surgery though only ~1700 receive this treatment yearly
The study strongly demonstrates that the comorbid conditions associated with obesity are underdiagnosed. In some cases this is because the screening is not done; yet, in other cases, despite screening, comorbid conditions go undiagnosed. For example, the prevalence of hypertension based on having at least 3 elevated BP measurements was 10 times higher than the prevalence based on the diagnosis being made (ICD 10) codes
My take: A lot of kids meet criteria for bariatric surgery but few undergo this surgery. If effective anti-obesity medications become more widely adopted (affordable), this may be a preferable option to surgery, especially in the pediatric age group. Surgery could be deferred to those who did not respond. Also, immediate implications of the study are that we need to be more diligent about looking for associated health problems (eg. OSA, HTN, T2DM, MASLD).
SL Gortmaker, SN Bleich, DR Williams. NEJM 2024; 390: 681-683. Childhood Obesity Prevention — Focusing on Population-Level Interventions and Equity
Despite the exciting advances in obesity pharmacology, most children and adults are unlikely to benefit from these expensive therapies anytime in the near future.
This commentary’s key points:
“Scholars and policymakers shouldn’t lose sight of population-level strategies that can prevent excess weight gain and obesity among children in the first place.”
The authors identify three successful policy examples: 1. Revision of WIC food packages to improve nutritional quality at a cost about $18 per child. 2. Improving school lunch standards (2010 Healthy, Hunger-Free Kids Act) at a cost of about $30 per child. 3. Excise tax on sugar-sweetened beverages. “In California, an analysis found that such a tax would be cost-saving, would prevent 42,700 cases of obesity in children and 223,000 cases in adults statewide over 10 years because of projected reductions in consumption of sugar-sweetened beverages.”
“Leveraging these strategies won’t fix the problem of childhood obesity overnight, but it could (and has already begun to) slow the development of new cases, particularly among members of historically underserved populations — a major public health achievement.”
My take: There is not a simple solution for widespread obesity in children and adults. We need to chip away at this problem from every angle. It is crucial to use public policy changes as one of our tools.
Recently, Dr. Shruthi Arora, an Emory Pediatric Endocrinologist and part of CHOA’s Strong4Life team, provided a terrific review of pediatric obesity pharmacology for our group.
Here are a few slides from Dr. Arora’s lecture:
General points from this lecture:
GLP-1 agents are a huge advance but currently limited by affordability (frequently there is a lack of insurance coverage if there is not T2DM) and availability. In addition, most individuals will regain weight loss when these agents are stopped.
GLP-1 agents are not recommended in the following: patients with gastroparesis, and patients with a personal or family history significant for MEN 2 A /MEN 2 B/ Medullary thyroid cancer
Long-term data is still needed. These agents have been associated with muscle and bone loss; thus, working to assure a good diet is still very important
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NASPGHAN has a good review/webinar on this topic as well: Pediatric MASLD in the Current Era of Pharmacological and Surgical Obesity Treatment Options. For members, after sign in, you can register and login to this webinar (look under clinical practice tab). This webinar made a lot of useful points (many covered by Dr. Arora too).
For GLP-1 agents, due to effects on gastric emptying, they are generally held prior to anesthesia. If they are given weekly, then hold 1 week prior to anesthesia. If it is a daily medication, hold for 1 day prior to anesthesia.
Surgery definitely helps improve MASH -though variable responses in patients. SLEEVE gastrectomy is currently the most frequent bariatric surgery
There is trouble getting GLP-1 medications.
Limited knowledge regarding long-term effects of cycling of GLP-1 agents.
Obesity is a long-term disease –>anticipate long-term treatment
The Wall Street Journal recently published a personal account of using the newer obesity medications. Bradley Olson, 1/12/24: A Weight-Loss Drug Changed My Life. Will It Solve My Problem? (behind a paywall). This article discusses the dramatic improvement experienced by the writer along with his concerns about the cost of the medication and potential for rebound when he can no longer afford it. Two of the figures:
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This is a terrific review of obesity and current management options, including surgery and medications. The review provides a thorough explanation of some of the reasons why we are having so many more children with obesity. The article personalizes the problems by focusing on one teen, Alexandra, who underwent sleeve gastrectomy.
Here are a few excerpts (from this lengthy article):
In response to so many grim facts, the A.A.P. in January released its first “clinical practice guideline” for those who care for children who have obesity. The academy now recommends that they immediately start “intensive health behavior and lifestyle treatment,” which it labels “the foundation” of obesity management; this approach supersedes the former strategy of “watchful waiting.” For older youth in certain circumstances — those with a higher B.M.I., say — drugs and, in cases of severe obesity, surgery should be made available as options...
The tenacity ofbody weight can be traced to our biology. Humans evolved to resist losing body fat so that we don’t become extinct, says Rudolph Leibel, chief of the pediatric molecular genetics division at Columbia University’s medical center…
A small number of children with severe obesity are born with leptin deficiency, a gene mutation identified by Sadaf Farooqi, a professor at the University of Cambridge’s Institute of Metabolic Science. Their appetites seem to be bottomless. Though it’s rare, Farooqi cites the extreme effect of this mutation as a clear illustration of the “very strong” impact that biology has upon appetite….Ghrelin, a hunger hormone, increases when food intake is restricted, making us eat more. Insulin, another important hormone, helps turn the food we eat into energy and controls things like blood sugar that influence how much we eat…“We don’t decide whether we’re going to be hungry or not, whether we’re going to have a craving or not….
Genetics may determine more than 70 percent of children’s body weight…But if our genes didn’t change significantly in the last century, why, then, are children getting bigger?No one knows for sure. One likely explanation, however, is the evolutionary mismatch between our genes and our surroundings…
The amount of readily accessible food has expanded immensely, making it easier than ever to eat — open a phone app, say, or go to a drive-through. Plenty of Americans can consume as much as they want, whenever they want.
Today nearly 70 percent of what children eat is ultraprocessed food… Ultraprocessed foods appeal to parents too: They’re cheap, last for years in pantries and freezers and require little preparation. “All food companies are trying to sell products,” Nestle says. “That’s the system, and if the system makes kids fat, well, too bad. Collateral damage.”..Over the past few decades, the variety of food items in some supermarkets has risen to more than 40,000 from 7,000…
Adolescents who have had bariatric surgery — most of them white and female — experienced weight loss similar to what adults lost: around 25 percent of their B.M.I. And while nearly 90 percent of these teenagers needed diabetes medications before the operation, none did afterward…Only a tiny fraction of the teenagers with severe obesity who qualify actually receive the operation…
The latest glucagon-like peptide-1 receptor agonists — as a group, commonly referred to as Ozempic — are the true game changers, a class of drugs that are making possible a degree of weight loss not seen before with medications. The pharmaceutical company Novo Nordisk manufactures GLP-1s for weight loss, one of which is semaglutide and sold under the brand name Wegovy. (Ozempic is the brand name for a lower-dose version of semaglutide that is prescribed to treat diabetes)…
The major studies of children and these drugs have enrolled many fewer adolescent subjects than adults, but no new safety concerns have emerged. In addition to semaglutide’s principal side effects of nausea, vomiting and diarrhea — reported by two-thirds of study participants — more serious ones include gallstones and pancreatitis. Wegovy comes with a caution about possible thyroid cancer, and the F.D.A. mandates that it include a warning about the possibility of suicidal ideation, because it acts on the brain…If patients discontinue the medicines, the weight returns…older drugs in its class have been used to treat diabetes for nearly two decades. But for any new medicine, the long-term risks remain uncertain…
For now, most adolescents who qualify for semaglutide probably won’t be able to get the drug at all [due to cost and drug shortages]….
[At the same time] a greater awareness of the drawbacks that can accompany the medicalizing of obesity, have fueled popular body-positivity movements like Health at Every Size, which seek to disentangle weight from health…
But despite the risks that can accompany obesity treatments — and despite the fact that the data doesn’t always present a clear picture — the prevailing attitude within the medical establishment is that, on balance, the potential negative consequences of obesity are too evident to ignore
Eric Topol: “The GLP-1 and now triple G-Agonists are exceeding expectations as weight loss drugs. Benefits for cardiovascular outcomes, possibly Type 1 diabetes, addiction, and more are reviewed in the latest Ground Truths.” His newsletter also describes the early results of these medications with MASH/NASH with improvement in ~90%.
To get the full review, go to Ground Truths: http://erictopol.substack.com (can sign up to get regular emails on many current medical topics)
Until a few years ago, I had controlled my depression and anxiety through decades of counseling. I was reluctant to try medications because the medical understanding of them seemed vague…We also can’t explain why some people benefit from S.S.R.I.s and others do not. Because of this, many people still believe those who take them don’t really need them. I also believed that, if I was strong enough, I didn’t need medication…
I was wrong to doubt. It’s had a remarkable effect on my mood, and almost everyone around me noticed the difference. I was more optimistic, friendlier and more engaging. I was forced to reconsider why I had avoided taking the medication for so long. I think it’s because — even though I realize this isn’t true — taking it felt like an admission of failure…
I’ve recently faced a similar scenario with new drugs for obesity. I’ve struggled with my weight for most of my life. I’ve always been overweight, and in the last few years, I’ve slipped into obesity, according to my body mass index. I exercise regularly and carry the weight well, but it bothers me immensely. It especially troubles me because I have a fair amount of self-discipline and eat quite healthfully…
Despite all the advances in science, we don’t know why some people, even when they try desperately, can’t seem to lose weight. Because of that, we often assume it must be a lack of willpower…
These drugs are expensive, but I was determined to see what would happen if I took one. It is hard to explain what life is like on this medication to people who don’t have trouble controlling their weight. I’m not hungry all the time. I’m not thinking about food incessantly. I’m not obsessing about what I wish I could eat and what I can’t. My mental health, and even my temperament, improved so much that my whole family rejoiced…
Before writing this essay, I had told just a few people I’m on the drug. I think it’s because, on some level, I still feel shame. I felt the same when I finally started taking an antidepressant…
Medical treatments should not be dismissed just because we don’t fully grasp their mechanisms; people who use them are not cheating.
“That’s all well and good in practice… but how does it work in theory?” I saw this quote many years ago when I was visiting the University of Chicago.
This quote came to mind as I was reading this article which showed relatively little change in the efficacy between more and less stringent elimination diets for eosinophilic esophagitis. This meta-analysis included 915 children and 847 adults and assessed the efficacy rates of 4 major dietary treatment regimens in eosinophilic esophagitis: 6-food (SFED), 4-food (FFED), 1-food (OFED), and a targeted elimination diet (TED).
Key findings:
The overall rate of histologic remission was 53.8% and in the individual dietary groups was 61.3% for SFED, 49.4% for FFED, 51.4% for OFED, and 45.7% for TED.
The overall rate of clinical response was 80.8%, with response rates of 92.8% for SFED, 74.1% for FFED, 87.1% for OFED, and 69.0% for TED.
Percentage of food antigen triggers identified via endoscopic and clinical evaluation after food re-introduction.
My take: It is clear to me that more restrictive diets can yield better response rates; however, in clinical practice they are difficult to maintain and this study shows that the improvement with more food restrictions may be quite limited.
Another reference on eosinophilic esophagitis: CJ Ketchem et al. Clin Gastroenterol Hepatol. 2023 Aug;21(9):2252-2259. Open Access! Higher Body Mass Index Is Associated With Decreased Treatment Response to Topical Steroids in Eosinophilic Esophagitis. Key finding: Histologic response (n=296) to topic steroids was higher for those who were nonobese compared with obese at fewer than 15 eosinophils per high-power field (61% vs 47%; P = .049); in addition, nonobese patients had significantly greater endoscopic and symptomatic responses.
S Wharton et al. NEJM 2023; DOI: 10.1056/NEJMoa2302392. Daily Oral GLP-1 Receptor Agonist Orforglipron for Adults with Obesity
In this phase 2 randomized, double-blind trial with 272 adults with obesity (mean weight at baseline 108 kg), participants were randomly assigned to receive orforglipron at one of four doses (12, 24, 36, or 45 mg) or placebo once daily for 36 weeks. “The pharmacokinetic profile of orforglipron, with a half-life of 29 to 49 hours, supports once-daily oral administration.”
Key findings:
At week 36, the mean change ranged from −9.4% to −14.7% with orforglipron and was −2.3% with placebo.
A weight reduction of at least 10% by week 36 occurred in 46 to 75% of the participants who received orforglipron, as compared with 9% who received placebo.
Adverse events reported with orforglipron were similar to those with injectable GLP-1 receptor agonists.
Weight reduction of at least 10% at week 36:
My take: This is an exciting time for drug development for obesity. Given the low success rates of traditional ‘lifestyle’ management approaches, these medications have the potential to reduce a great deal of morbidity. Oral agents, rather than injections, would hasten the use of these agents more broadly. Long term outcomes are still unclear.
AM Jastreboff et al. NEJM 2023; DOI: 10.1056/NEJMoa2301972. Triple–Hormone-Receptor Agonist Retatrutide for Obesity — A Phase 2 Trial.
Background: Retatrutide (LY3437943) is an agonist of the glucose-dependent insulinotropic polypeptide, glucagon-like peptide 1, and glucagon receptors.
Methods: This study enrolled 338 with BMI of at least 27 in a a phase 2, double-blind, randomized, placebo-controlled trial with once-weekly injections of retatrutide.
Key Findings:
The number who achieved at least a 10% weight loss:
“The safety profile of retatrutide was consistent with reported phase 1 findings in persons with type 2 diabetes13 and similar to those of therapies based on GLP-1 or GIP–GLP-1 for the treatment of type 2 diabetes or obesity”
My take: There are a number of effective agents for obesity that have been developed very recently. Long term efficacy and safety are still not well-understood.
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