TOPIC · WEIGHT LOSS DRUGS

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Did you know – Weight loss drugs

  • Weight loss medications tend to work via one or more of these mechanisms:

– reducing appetite, making you feel fuller, so you eat fewer calories
– reducing the absorption of nutrients, such as fat, making you take in fewer calories
– increasing metabolism, making you burn more calories

  • When paired with other lifestyle changes and taken under the supervision of a healthcare professional, these drugs may offer an effective way to lower your weight.
  • Important to emphasize that these medications should be combined with a balanced weight loss diet and exercise regime
  • On their own they’re not a helpful long-term solution for obesity and may lead to weight regain over time.
  • They also have many possible side effects, some of which can be serious.
  • Common Side effects:

– Nausea
– Vomiting
– Diarrhoea
– Dizziness
– Headaches
– Increased heart rate
– Infections
– Indigestion

  • Uncommon, severe side effects

– Gastroparesis – stomach paralysis
– Kidney problems
– Thyroid C-cell tumours
– Gallbladder disease
– Low blood sugar
– Suicidal thoughts

  • Before 2012, there were few approved weight loss medications
  • The top medications at that time were

– Appetite suppressants
– Lipase inhibitors – reduction in fat digestion

  • Today the advent of Glucagon-like peptide-1 receptor agonists (GLP-1 receptor agonists), has attracted explosive media attention.
  • GLP-1 agonists are currently considered the most effective anti-obesity medications and are considered safe for long-term use.
  • GLP-1 receptor agonists like

– Wegovy
– Saxenda
– Zepbound

  • Determining if you are a candidate for weight loss medications begins with BMI.
  • Most medications are prescribed for someone with

– a BMI of 30 or greater
– a BMI of 27 or greater if the person has weight-related health conditions.

  • Most weight loss medications are approved for adults only,
  • Semaglutide, liraglutide, and orlistat are now approved for children aged 12 and older.
  • All weight loss medications are contraindicated for pregnancy.
  • Some weight loss medications have been on the market for many years, and new ones emerge frequently
  • BUT here’s the thing – prescription weight loss medications, including GLP-1 agonists, may be effective for some
  • But other lifestyle changes are still necessary for long-term success
  • Do they work long-term is the question everyone is asking the answer at the moment looks like only if you keep taking the drug
  • But a Danish Study from Feb this year states “Our study offers new hope as we have shown that the majority of those who take weight loss medication and exercise regularly are able to maintain the beneficial effects a year after treatment termination.” –  Signe Sørensen Torekov
  • The study also demonstrated that those just taking the GLP-1 increased in weight again
  • If you regard these medications as a tool to help you change to a healthier lifestyle and diet, they’re like any other tool, if you use it the right way, it works. If not, it doesn’t work.”
  • What are the long-term side effects?
  • The answer is no one knows as the drugs were released before any long-term trials were completed
  • The longest trial of 7 years was looking at their impact on T2D not weight loss by monitoring HbA1c levels, not appetite, stomach function, etc
  • Many health experts are saying the drugs are

– A kick start or jump start
– People need a little win
– Little helper
– Adjunct to other therapies – diet and exercise

  • The elephant in the room that still needs addressing is the type of food
  • These drugs effect the quantity of food ingested, which is absolutely part of the problem but quality ie. what these foods contain ie chemicals and what they don’t contain ie. nutrients has not been addressed
  • Experts from many fields of health are adamant that until the food industry get the same ‘treatment ‘ as the tobacco industry obesity (and lifestyle disease) will continue climbing.

Meet Sally and get to know all about obesity

Intro obesity week

What is obesity

Measuring obesity

The cause of obesity

Hypothalamus

Current Weight Loss Drugs

Semaglutide

  • Wegovy and Ozempic
  • GLP-1 receptor agonist

Tirzepatide

  • Zepbound and Mounjaro
  • GLP-1 receptor agonist

Liraglutide

  • Saxenda
  • GLP-1 receptor agonist

Phentermine

  • Adipex and Suprenza
  • Appetite suppressants

Phentermine-topiramate

  • Qsymia
  • Appetite suppressants

Naltrexone-bupropion

  • Contrave
  • Opioid and antidepressant

Setmelanotide

  • Imcivree
  • Receptor modulator

Orlistat

  • Xenical and Alli
  • Lipase Inhibitors

Hydrogel

  • Plenity
  • One grain swells to 100 times its size in the stomach.

Endogenous Glucagon-like peptide-1 aka GLP-1

  • GLP-1 is a peptide hormone (made of protein)
  • It is produced and secreted by intestinal L-cells and certain neurons within the brainstem
  • Triggered by food consumption – fats, sugars and proteins
  • It’s job
  • Tell the brain that food is coming
  • Slow down the release of nutrients in the stomach to allow the small intestine time to breakdown and absorb the income of nutrients
  • So the stomach ‘drips’ nutrients slowly into the duodenum (the first part of the small intestine)
  • Decreases Glucagon production in the Pancreas, so the less liver releases less glucose into the blood stream
  • Increases Insulin production
  • So all in all blood glucose levels decrease
  • Increases satiety signals in the hypothalamus
  • GLP-1 receptor activation in the brain has also been linked with neurotrophic effects including neurogenesis and neuroprotective effects including reduced cell death and dysfunction.
  • In the diseased brain, GLP-1 receptor agonist treatment is associated with protection against a range of diseases, such as Parkinson’s, Alzheimer’s, stroke, traumatic brain injury and MS.

GLP-1 Agonist Drugs

  • Three GLP-1 agonists have been approved for weight loss, including

– Liraglutide – Saxenda
– Semaglutide – Wegovy
– Tirzepatide – Zepbound

  • All three are available as a self-administered injection

– Saxenda is administered once daily
– Wegovy and Zepbound once per week.

  • Though not approved specifically for weight loss, some other GLP-1 agonists intended to treat type 2 diabetes were / are sometimes prescribed off-label for weight management, including:

– Semaglutide – Ozempic or Rybelsus
– Dulaglutide – Trulicity
– Liraglutide – Victoza
– Exenatide – Byetta
– Exenatide extended-release – Bydureon BCise
– Tirzepatide – Mounjaro

  • GLP-1 agonists are only available through a prescription from a doctor or other qualified healthcare professional.
  • Several telehealth services and weight loss programs may also provide prescriptions if you meet the eligibility criteria.

Criteria

  • Approved for use

– BMI ≥30 for adults
– BMI ≥ 95th percentile for age and sex for children
– BMI ≥27 with weight-related medical problems.

  • The dose must be increased gradually over 16 to 20 weeks to arrive at the 2.4 mg dosage.
  • This progression can help to alleviate side effects, which include:

– Gastrointestinal symptoms
– Headache
– Dizziness
– Fatique

How it works

  • GLP-1 agonists work by

– Slowing the emptying of the stomach
– Increasing feelings of fullness
– Reducing the secretion of glucagon, a hormone involved in increasing appetite.

Effectiveness

  • Several studies have found that GLP-1 agonists could be beneficial for weight management.
  • One study with 1,961 adults found that taking 2.4 milligrams (mg) of Semaglutide per week combined with lifestyle changes resulted in a nearly 15% reduction in body weight after 68 weeks.
  • Another small study found that people taking liraglutide lost an average of 17.2 lb (7.8 kg) over 6 months.
  • More recently, a 2023 phase 3 clinical trial in 2,539 adults found that people taking tirzepatide lost 20% or more of their weight over the course of 72 weeks.

Common Side effects

  • Nausea
  • Vomiting
  • Diarrhoea
  • Dizziness
  • Headaches
  • Increased heart rate
  • Infections

Uncommon, severe side effects

  • Gastroparesis – stomach paralysis – an average of 70 minutes for half the food they’d eaten to exit their stomachs, compared to just four minutes among unmedicated controls. In some, it took more than two and a half hours for half of their food to be digested. The greater the delay in food leaving the stomach, the greater the weight loss, but at what cost?
  • Kidney problems
  • Thyroid C-cell tumours
  • Gallbladder disease
  • Low blood sugar
  • Suicidal thoughts.
  • More research is also needed on the long-term effects of these medications, as there’s concern about potential weight regain over time.

Contraindications

  • Multiple endocrine neoplasia (MEN) syndrome type 2,
  • History of thyroid cancer
  • History of pancreatitis
  • Pregnancy
  • Current use of certain prescription medications.
  • People with severe gastrointestinal conditions, such as gastroparesis and inflammatory bowel disease.

NB!

ALL GLP-1 Agonist should be used in combination with diet and exercise.

NB!

The underlying basis for their success is Calorie Restriction plain and simple.

How Effective are GLP-1 Drugs

  • These medications should ONLY be used alongside dietary changes and lifestyle modifications, such as regular physical activity.
  • Not only will adopting dietary and lifestyle changes help increase the effectiveness of weight loss drugs, but they may also help minimize weight regain, which often occurs after you stop taking these medications.

Lets look at the numbers

  • Compared to lower calorie intake combined with exercise not a better job
  • And none of studies are looking at which tissue is lost ie. is the weight loss because of fat or muscle loss
  • And that is important

Examples

Exenatide (GLP-1 for T2D) for 1 year

  • Obesity – down 5.1 kilos
  • PCOS – down 3.2 – 6 kilos
  • Syndrome – down 3.7 kilos

Liraglutide (Victoza for t2D) for 2 years

  • down 4.8 – 7.2 kilos

Semaglutide for 68 weeks + 150 mins exercise a week and 500 calorie deficit

  • Down 6.9 – 15.3 kilos

NB!

Losing these kilos also involved nausea and vomiting which in the long run can lead to food aversion

Long-term coherence and maintenance

  • 50% stopped after 1 year
  • 70% stopped after 2 years

Why?

  • Because of the side effects
  • And weight loss isn’t as much as they had been led to believe

Potential side effects no one is talking about

  • Nutrient deficiency increasing the risk of:

– Low bone density
– Loss of muscle mass an strength
– Increases production of cortisol and other stress hormones
– Decrease Thyroid activity
– Decrease sex steroids aka testosterone and estrogen = infertility.

Natural Ways to Increase GLP-1

  • Colonize your gut with Akkermansia muciniphila
  • This bacterium naturally secretes a GLP-1-inducing proteins that increase GLP-1 secretion.

Akkermansia-Boosting Strategies

  • Supplement with specific probiotics and prebiotics, to promote Akkermansia growth in the gut including

– Lactobacillus rhamnosus
– Bifidobacterium animalis
– Lactococcus lactis
– Oral fructo-oligosaccharides FOS

  • Eat more fibre

– The short-chain fatty acids that form from fibre as it ferments in your intestines feed beneficial bacteria, including Akkermansia.

  • Increase FODMAPs

– including fructose in fruits
– lactose in milk and some dairy

  • Boosting intake of dietary polyphenols

– Black tea
– Red grape extract
– Cranberry extract
– Concord grapes – grown in the US

  • Avoid

– alcohol
– high-fat diets – 60% fat or higher

  • Berberine is another natural option:

– A compound that’s extracted from goldenseal, barberry, Oregon grape and tree turmeric.
– Some are even calling it “nature’s Ozempic,” as it helps regulate blood sugar and improve insulin sensitivity and gut microbiome diversity that may contribute to weight loss.
– A 2022 systematic review found that 1g per day of Berberine reduced insulin levels.
– Insulin sensitivity and weight loss are strongly associated
– Berberine, which functions like metformin, a commonly used medication in the treatment of diabetes.

Pros and Cons of GLP-1 Drugs

Pros

  • Effective for weight loss when used alongside dietary changes and regular physical activity
  • Approved by FDA for weight management
  • Might offer other health benefits, including improved blood sugar, blood pressure, or cholesterol levels
  • Many medications available through telehealth platforms

Cons

  • Not suitable for everyone
  • Some medications may be expensive, depending on insurance coverage
  • Can cause side effects, some of which may be serious
  • Weight regain is possible once medication is discontinued
  • More research needed on long-term health effects.

The Elephant in the Room

  • The terms “processed” and “ultra-processed” are thrown around a lot and are usually associated with something negative
  • But not all processing is new or negative
  • Processing food means changing its natural state to

– prolong its shelf life
– make it safe to store or eat
– enhance its taste
– increasing its nutrient availability aka making it easier to digest

  • Common forms of processing

– Pasteurizing, steaming or boiling
– Canning
– Fermenting
– Freezing
– Drying
– Smoking

  • Ultra-processed foods are entirely altered and are not foods
  • The body has never seen these molecules throughout the millions of years man has existed
  • They have high levels of

– unhealthy fats
– refined sugars
– salt

  • They also undergo industrial processes, like

– Hydrogenation
– Moulding

  • They contain additives like

– Dyes
– Stabilizers
– Flavour enhancers
– Emulsifiers (mix fats with liquid/water – dressings ,mayo, margarines, etc)
– Defoaming agents – often silicone (reduce foaming caused by proteins or gases that may be interfere with processing – Coke, Sprite, and other cold drinks contain defoaming agents)

  • They are very calorie-dense but don’t contain many, if any, valuable nutrients.
  • They are engineered to be convenient, extra tasty, and highly profitable for the companies that make them.
  • Science is VERY clear here – eating UPF’s is not good for your health or weight
  • Processing changes the complex structure of nutrients in a food, known as the food matrix.
  • Science shows that changes in the food matrix alter the way our bodies respond to food, potentially putting us at risk of various health conditions.
  • A 2019 French study analysed the diets of more than 44,000 French adults for 7 years and found that high consumption of UPF’s was linked with an increased risk of death.
  • A 2019 Spanish study of almost 20,000 adults in Spain had similar findings.
  • Another 2019 French study of over 100,000 French adults followed over 5 years showed that eating more UPF’s was linked with a greater risk of heart disease.
  • A similar analysis of the same participants found that a 10% increase in UPF consumption was linked with a 12% higher risk of cancer.
  • Question that needs to be answered

– Why are they still available?

  • Scientific Answer

– Although these studies were significant, their observational nature cannot prove cause and effect

  • Cynical answer

– Money

2019 French study – READ MORE

2019 Spanish study –  READ MORE 

2019 French CV study – READ MORE 

Upcoming Weight Loss Medications

  • With intense consumer demand for weight loss medications, combined with rising obesity rates, more medications are bound for the market in the coming years.
  • The new direction for obesity treatment is,

– treating it more as an endocrine disease
– treating it hormonally
– giving patients and providers different options to choose the drug that will be the most useful

  • Researchers continue to seek hormones that play a role in appetite, such as peptide YY
  • Lilly is developing

– Orforglipron, an oral GLP-1 agonist
– Retatrutide, another injectable, targets GLP-1, GIP, and glucagon.

  • Pfizer is also developing

2 GLP-1 agonists that can be administered as pills.

  • Amgen is trialling

– a drug candidate that is both a GLP-1 receptor agonist and a GIP receptor antagonist, as opposed to a dual agonist like semaglutide.

  • Monoclonal antibodies are another “hot” category in drug development for a range of diseases, including obesity.
  • For example

– Bima-gru-mab is being studied as an infusion to increase muscle mass while decreasing fat.

  • With more options available, doctors will be increasingly able to personalize treatments as they match patients to the medications that will work best for them.

NB! – we’re still avoiding the elephant in the room.

Medications that Can Cause Weight Gain

  • There are many medications that can be obesogenic or can cause weight gain.
  • These medications can potentially cause variable weight gain in some individuals.

– Some beta-blockers
– Calcium channel blockers
– Anti-diabetes medications such as insulins, sulfonylureas, thiazolidinediones, and meglitinides
– Hormone therapies such as glucocorticoids and injectable progestins
– Anti-seizure medications, including carbamazepine, gabapentin, valproate, and pregabalin
– A wide variety of different antidepressants
– Some mood stabilizers
– Migraine medications such as amitriptyline and paroxetine
– Some antipsychotics
– Chemotherapeutic and anti-inflammatory agents.

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