IM/ACP 2022: What has been working for obesity?

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One of the topics discussed in the afternoon of the last day of the Internal Medicine Meeting (IM/ACP 2022) of the American College of Physicians it was obesity. A subject until some time ago “forgotten” in clinical practice due to the relative difficulty in establishing a treatment, but which has been gaining ground more and more with the advancement in therapies and knowledge about medications, the long-term benefits of surgical treatments and increasingly understanding the importance of intervening in a pathological condition that is the basis for several metabolic changes, such as insulin resistance.

For this, Dr Adrienne Youdim, internist, professor at UCLA (and owner of the HealthBite podcast) brought a very global approach to obesity for the clinician in her lecture.

patient standing on a scale with tape measure in front to measure obesity BMI

Obesity

42% of the American population is obese, that is, a BMI greater than or equal to 30 kg/m², with 9% being severely obese (BMI greater than 40 kg/m²). These data are based on surveys from 2017 to 2018, published in JAMA, and therefore still without considering possible impacts of the pandemic. And why is obesity on the rise?

First, it is a multifactorial disease. Of course, the first and most important factor is the caloric imbalance, with intake greater than expenditure. However, there are several factors that interfere with weight gain, leading to increased appetite and minor changes in metabolism. Factors that can interfere in these variables are: microbiota, the circadian rhythm of work, feeding schedule, medications, genetics and epigenetics and even childhood trauma. In addition, there is great difficulty in losing weight also for several reasons, from motivational, social, to physiological: our body is programmed to maintain weight and conserve energy.

There are several short-term and long-term markers of appetite homeostasis. Briefly, in the short term, several signalers such as GLP-1, PYY and amylin are anorectic, that is, they act on central appetite control pathways in order to inhibit it. Among the long-term controllers, the main one is the hormone leptin, produced by fat cells and also acting on the central pathways of appetite, signaling satiety.

But we don’t just eat out of physiological need. The limbic system also plays a crucial role, being responsible for the “hedonic appetite”, controlled mainly by dopamine, integrating affective memories, will, pleasure, the sensation of reward and the “craving”. Still, we don’t just eat out of desire or need, but there is also the stress factor: when we are subjected to conditions like this, there is evidence that there is an increase in ghrelin, which is known to be orexigenic (that is, it increases appetite).

Weight loss and maintenance

But obesity is not math. Losing weight is not like gaining it. Several factors interfere:

  • People who lose weight have higher levels of ghrelin. A loss of about 10% of weight following a low-calorie diet increases ghrelin levels by 30%, even one year later! That is, in practice, people who lose weight are actually more hungry.
  • Several anorectic flags (GLP-1, PYY) on the other hand, fall
  • With the reduction of adipose tissue, there is less production of leptin, also reducing the important anorectic signaling of this hormone.
  • And not mentioned in the lecture, but it is worth remembering that weight loss leads to an obvious reduction in the basal metabolic rate, since there is a reduction in the amount of tissue, making it even more difficult, since it will be necessary to maintain a more restricted diet to keep up the pace of weight loss.

Interventions: diet

First message: studies comparing different diet strategies show no differences in weight loss between them. This month a study on intermittent fasting vs calorie restriction was published in the NEJM, with no difference. She goes on with several examples. What matters, in the end, is the restriction on the amount of calories ingested. What else might work?

Evidence shows that diets with higher protein intake increase satiety and reduce the chance of “snacks” afterwards (however, it is worth remembering that the proportion between the different macronutrients is not the determining factor in weight loss). Having an adequate protein intake even within the diet can, on the other hand, preserve lean mass, mitigating its loss and increasing the proportion of fat loss (remembering that in the slimming process, we lose both fat and lean mass).

An average intake of 80g of protein per day in a diet can result in a 30% loss of mass/70% of fat, while 40g can cause the loss of up to 58% of lean mass.

Physical activity

The message is clear: physical activity, in general, is not responsible for weight loss, but essential for weight maintenance. It is important to emphasize that physical activity is essential in maintaining lean mass, which contributes to improving the basal metabolic rate.

Sleep

Observational studies show that there is a greater tendency to gain weight the less sleep an individual has per night. In physiological studies, 2 days of sleep deprivation are enough for a rearrangement of hormones and appetite signals to occur: -18% leptin, +28% ghrelin, +24% hunger, +32% appetite for highly palatable foods (who has never left of a shift where he didn’t sleep and the next day he “gifted” himself with a more caloric food?)

anti-obesity medications

All measures must be used. When combined with proper guidance, they have a very important impact on controlling this condition. Always indicated in the management of individuals with BMI > 30 kg/m² or BMI > 27 with at least one obesity-related comorbidity. The goal from a medical point of view is a loss of between 5 and 10%. And where do these magic numbers come from?

Several studies show that there is an improvement in HbA1c, BP, cholesterol, TG, OSAHS, quality of life and even reversal of infertility.

About medications, Dr. Adrienne Youdim addressed those approved by the FDA (which is why she included phentermine and the phentermine/topiramate combination, but did not address sibutramine). Briefly, the highlights:

Orlistat:

  • It is an inhibitor of gastric and pancreatic lipase;
  • Side effects: flatulence, fecal urgency, steatorrhea;
  • Contraindication: malabsorptive diseases;
  • 120 mg 3x/day before meals.

Bupropion/Naltrexone (recently approved in Brazil):

  • Dopamine/noradrenaline reuptake inhibitor + opioid antagonist;
  • Side effects: nausea, vomiting, headache, constipation, dizziness;
  • Contraindications: epilepsy or seizures, anorexia, bulimia, use of MAOIs, abstinence/weaning from alcohol and drugs;
  • Dose: 8/90 mg 1x/d in the first week; increases 1 cps/day per week, reaching 2 cps 2x/day (avoid nausea, headache and dizziness).

Semaglutide:

  • GLP-1 agonist, initially designed to control diabetes, reducing gastric transit and signaling satiety;
  • Side effects: nausea, vomiting, constipation;
  • Contraindications: medullary thyroid carcinoma and multiple endocrine neoplasia 2;
  • Dose: 0.25 mg 1x/week, with progressions every 4 weeks. Currently, the FDA has approved doses of up to 2.4 mg/week (in Brazil, Ozempic goes up to a dose of 1 mg).

*Daily liraglutide is also available, but there are already studies comparing both medications, showing greater efficacy in the use of semaglutide. We reviewed this study here on the Portal.

** Remembering that all medications must be prescribed by a doctor with adequate follow-up.

Surgery

How many have heard the phrase “I don’t believe in surgery”? In science there is no room to believe it or not – there are miles of evidence showing benefits in hard outcomes when using surgery in people with an indication. And what would they be?

BMI > 40 kg/m² or BMI > 35 kg/m² with one or more obesity-related comorbidities.

It is important to emphasize that there are metabolic benefits that go beyond weight loss, such as a reduction in ghrelin levels after surgery, an increase in GLP-1 and PYY. There is a reduction in mortality, in addition to better control of diabetes (leading to remission in some cases), hypertension and other risk factors.

Obesity bias

Worst of all: studies prove that patients with obesity suffer prejudice even from multidisciplinary health teams. This has a direct impact on your care.

Final message

Today, there are several tools that we can and should offer our patients. The treatment of obesity should be one of the pillars of care, especially when we think about reducing the risk of events and improving quality of life.

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About Jenni Smith

She's our PC girl, so anything is up to her. She is also responsible for the videos of Play Crazy Game, as well as giving a leg in the news.

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