Body Composition and Weight Management

What are four different treatment options for individuals who have excess adiposity and health risk?

1. behavioral interventions

2. nutrition interventions

3. pharmacology interventions

4. surgical interventions

Who should receive bariatric surgery?

those with a BMI = 35-40 with comorbidities who have not had success with other treatments

Who should take weight loss medications?

those with BMI 30+ or > 27 with co-morbid conditions

Is diet or exercise the best way to lose weight?

need a comprehensive plan that includes diet physical activity, behavior change, such as aerobic exercise

How can weight loss be maintained?

continue doing behaviors that led to weight loss

• > 200-300 min/week

What are the health benefits of modest weight loss (5-10%)?

help to reduce obesity related co-morbidities

What improvements can you see with 3% BW loss?

Blood glucose and triglycerides lowering

What improvements can you see with 5% BW loss?

improvements in HDL-C, total cholesterol, BP and quality of life

What improvements can you see with 10% BW loss?

improvements in sleep apnea and fatty liver

What improvements can you see with 10-15% BW loss?

decrease CVD events

What improvements can you see with 15% BW loss?

remission of T2DM

What treatment mode is associated with 3-7% BW loss?

lifestyle modifications

What treatment mode is associated with 5-10% BW loss?

first generation medications

• pills that target neurotransmitters and brain activity

What treatment mode is associated with 15-22% BW loss?

second generation meds (10 years or so)

• ex: GLP-1

What treatment mode is associated with 20-35% BW loss?

obesity surgeries

Describe how most of the weight loss medications in 1930-1960s worked?

mostly stimulants which acted to increase metabolism and decrease hunger

Describe how most of the weight loss medications in 1990s-2014 worked?

most target brain neurotransmitters (serotonin, dopamine) to lessen hunger and increase sensation of fullness

• anorectic drugs: lessen hunger

• orlistat: decreased fat absorption in GI tract

• had limited effectiveness in overall body weight loss

Describe how most of the weight loss medications in 2014-2026 work?

target gut hormones and incretins (GLP-1) which act at level of the GI tract and at regions of the brain; net effect are to lessen hunger, increase fullness by delaying gastric emptying, lower blood glucose levels

• injectable medication but more recently became pills

• much greater effectiveness in body weight loss and health benefits

How prevalent is GLP-1 use in the US?

12% of adults (1 in 8) have used it

• 6% are currently using it as of 2024-2025

What are the four categories of weight loss medications?

1. thermogenic substances

2. malabsorptive agents

3. appetite suppressants

4. hormone

Describe thermogenic substances and how they work in terms of weight loss.

activate the CNS, increasing heart rate, constricting blood vessels, expanding bronchial tubes → helps to promote heat produciton instead of energy storage

• ex: ephedrine

• FDA received reports of adverse effects such as cardiac arrhythmias and death → BANNED in 2004

Describe malabsorptive agents and how they work in terms of weight loss.

help to inhibit absorption of dietary fat OR dietary carbohydrate

• for inhibiting fat it does it through binding of GI lipase in the gut lumen, decreasing micelle formation

Example of fat malabsorptive agent.

• Orlistat (xenical or alli) Rx and OTC

What are some side effects regarding fat malabsorptive agents?

• decrease activity of pancreatic lipase

• fecal fat increases by 30%

• not as useful for low fat diets

• may decrease availability of dietary fat souluble vitamins

Example of carbohydrate malabsorptive agent.

Acarbose Rx

• used for diabetes management

Describe appetite suppressants aka anorectic drugs and how they work in terms of weight loss.

alter brain neurotransmitter metabolism, works on appetite centers in brain which can

• activate CNS as stimulant

• increase secretion of brain neurotransmitters (norepinephrine, dopamine, or serotonin)

• inhibit re-uptake of neurotransmitters

• may bind to 5HT receptor and act as agonist

What are examples of anorectic drugs?

• contrave

• qysmia

• belviq

• meridia

• OTC: dexatrim, phentermine, amphetamines (not as intense as the prescription level)

Describe hormones (GLP-1 agonist) and how they work in terms of weight loss.

decrease appetite through GLP-1receptors in hypothalamus, delaying gastric emptying (staying full longer)

• lowers blood glucose by increased insulin secretion and insulin sensitivity

• initially used for type 2 diabetes control

Why is GLP-1 called incretins?

bc it is a peptide hormone that is secreted by the ileal cells within the ileum of the GI tract

What are some examples of hormone weight loss medication?

injectables 1x a week

• ozempic (semaglutide) → GLP-1 agonist

• wegovy (semaglutide) → GLP-1 agonist

• zepbound (tirzepatide) → dual GLP-1 and GIP agonist

• mounjaro (tirzepatide) → dual GLP-1 and GIP agonist

daily pills everyday

• wegovy oral

• foundayo

What is Plenity?

hydro-gel capsule that releases cellulose particles (also has citric acid in it), these particles absorb water in the stomach and small intestine, expanding in size

• increases in bulk and signals satiety

• particles break down in colon and excreted in stool

• not considered a drug bc it is not absorbed

How often do you use Plenity?

3 capsules orally before both lunch and dinner with water

• used in BMI 25-40

• not that big of a difference compared to placebo

What is GLP-1?

endogenous hormone (incretin) that is typically released in very small amounts from the ileum (distal portion of small intestine) in response to meals

• very short half-life (2 minutes) due to rapid DPP-4 enzyme

• when circulating it acts on alpha cells and beta cells of pancreas to decrease glucagon secretion and increase insulin release respectively (helps in glucose control)

• was not made for long term weight loss, made to be a transient, not sustained satiety signal

Describe the pharmacologic approach to GLP-1 and how the medication differs in order to act as a GLP-1 agonist effective for long term weight loss.

• modified GLP-1 molecule to prevent DPP-4 degradation AND the pharmacologic dose is much higher compared to endogenous levels

  • result: injectable has half life of 7 days and takes 5 weeks for full clearance from body

  • promotes glucose control and weight loss through multiple mechanisms

Describe GLP-1 Agonist actions at different tissue levels (liver, intestine, brain, muscle, and pancreas) and how it supports weight loss.

• liver:

  • decreased gluconeogenesis

  • decreased steatosis (fat in liver)

• intestine:

  • decreased gastric emptying

  • decreased gastrointestinal motility

• brain:

  • decreased food intake

  • decreased reward behavior

  • decreased palatability

• muscle:

  • increased sensitivity

  • increased glucose uptake

• pancreas

  • increased insulin secretion

  • increased insulin synthesis

  • decreased glucagon secretion

  • decreased apoptosis

  • increased beta cell survival

Characteristics associated with Wegovy.

• approved for weight loss

• GLP-1 agonist (higher dose of ozempic, originally used for type 2 diabetes)

• 5-20% change in BW

• 75% of patients lost at least 5% of BW

Characteristics associated with Zepbound.

• approved for weight loss

• dual incretin against GLP-1 and GIP-1

• same drug as Mounjaro that is approved for Type II diabetes

• more effective than Wegovy

• 15-25% change in BW

• 85-90% of patients lost at least 5% BW

Overall what are the effects of GLP-1 on the brain, tissues, vascular, and stomach?

• brain:

  • central appetite suppression via hypothalamic pathways

  • reward center modulation

• tissues:

  • improved blood glucose control

• vascular:

  • anti-inflammatory and cardioprotective pathways

• stomach: delayed gastric emptying, feeling of fullness and satiety

What are the common side effects associated with GLP-1 use?

What is sarcopenia? How do GLP-1 increase the risk of sarcopenia?

disproportionate loss of muscle mass

• rapidity of weight reduction and low protein consumption due to lack of appetite may contribute to muscle loss and increased risk of sarcopenia

What are the protein requirements for those on GLP-1?

• 1.2-1.6g/kg/day

• don’t fall below 0.4-0.5 g/kg/day

What are some meal recommendations surrounding those on GLP-1?

• small breakfast and meals 3-4 hours

• drink fluids, ginger, peppermint tea to mitigate side effects

• small frequent meals

What is unknown in regard to GLP-1s?

• longer term safety (use for >5-10 years is unknown)

• diet and lifestyle interactions

• diet quality and risk of nutrient deficiencies (don’t know if people change their diets for the better or just eat less overall)

• sustainability of weight loss and prevention of regain

During rapid weight reductions, what are 11 nutrients of concern?

• Fe

• Ca

• Mg

• Zn

• Vitamin A, D, E, K, B1, B12, and C

In terms of the CRAVE study, what happens to diet quality when patients start GLP-1? What happens to food cravings on GLP-1 in a real world setting after following 28 new users for 24 weeks?

• see decreased caloric intake

• protein intake slightly below 1g/kg/BW and those with higher intake they had better preservation of skeletal muscle mass

• no improvement in diet quality

• modest or no change in cravings

What did the CRAVE study reinforce?

What is the overall trend seen in different obesity treatments?

initial weight loss seen with most all interventions but unfortunately weight regain often occurs

What obesity treatment seems to have greater success in terms of maintenance?

surgical interventions results in greater weight loss and tends to have greater success in maintenance

• diet approaches and physical activity can achieve similar results but only when activity is 300min/week or more

What is more effective second gen medications or first gen?

second gen medications achieve significantly greater weight loss than older first gen meds

Why are GLP-1 and surgical approaches more successful than diet?

• diet approaches typically result in a plateau effect and slow regain of fat mass over time

• GLP-1 are better in maintaining weight loss bc they have interrupted some of the biological drive for restoration of fat mass (appetite is down-regulated, endocrine signals are modulated, or physiological changes occur in GI due to surgery)

  • weight gain does occur with someone stops taking the medicine whereas the surgery is more invasive but permanent

What is the criteria for weight loss surgery?

What are two types of bariatric surgeries?

1. gastric restriction

2. gastric bypass

What are two types of gastric restriction surgeries

1. vertical sleeve gastrectomy

2. gastric banding

Describe vertical sleeve gastrectomy surgery.

removes 80% of the stomach, and keeps the remaining portion (which is shaped like a banana

Describe gastric banding surgery.

device put around top of stomach creating a small pouch above band

• tends to be less effective on weight and related diseases

What are some characteristics in general associated with gastric restriction surgeries?

• increased fullness and decreased hunger

• average loss of 20% excess weight

• improves co-morbid conditions usually

• tends to have fewer intestinal complications than other weight loss surgeries

What is an example of a gastric bypass surgery?

Roux-en-Y Bypass

Describe the Roux-en-Y bypass.

• severely reduces size of stomach to hold 2tbsp of volume

• bypasses remainder of stomach and duodenum (called the biliopancreatic limb) as the mid jejunum is pulled up and attached to gastric pouch

  • the biliopancreatic limb is reattached to the jejunum

What is the general impact of gastric bypass surgery?

• increased fullness and decreased hunger

• average loss of 20-50% excess weight

• improves co-morbid conditions

• some intestinal malabsorption occurs

• can have sustained weight loss (20-30% is common)

What are two potential complications of the Roux-en-Y GB?

1. dumping syndrome

2. malabsorption

What is dumping syndrome?

rapid rush of liquid/soft high caloric food dumping into the limb of small intestine which can cause nausea, bloating, diarrhea, and weakness

What deficiencies can occur as a result of Roux-en-Y GB?

Fe, Ca, B12, and Mg

What could lead to weight regain with gastric bypass?

• expansion of gastric pouch is possible

• widening of gastro-jejunostomy connection

• adaptation of limb of intestine that received food (jejunum)

What are the different recommendations you have to abide by after bariatric surgery?

What are some mechanisms of metabolic change that lead to decreased in co-morbidities after surgery?