What are their roles in weight loss?

Semaglutide and Tirzepatide are the two latest weapons in our arsenal to fight obesity.  The obesity crisis around the world is at an all-time high.  In 2016, overweight people represented 39% of the population, and truly obese people represented 13% for totals of 1.9 billion and 650 million, respectively.  By 2022, the obese population alone had reached one billion.

What we can say is that it is not your fault that you are overweight.  It’s not even a conspiracy.  It is simply that we’re victims of our own physiology, and Semaglutide and Tirzepatide are going to let us change that, but first, let’s get some background to understand just what we’re up against.

Why Are We Fat?

As technology advances, so does calorie availability, as our farming and food production capabilities improve.  Unfortunately, the easiest and least expensive calories to produce are carbohydrates which the body quickly turns into stored fat. 

This mechanism is what allows animals (including humans) to survive when food is scarce.  Humans don’t really need this ability very often since we’re so good at producing food, but it’s part of our evolution and we can’t simply discard it.  When we eat more than we need, the body stores that excess energy, as fat, against future needs.

If protein and healthy fats cost the same as carbs, most of us would be a healthy weight with little difficulty, but that doesn’t happen in our economy.  Carbs are cheap to buy and fast to produce.  The bad part of that is that they don’t flip the satiety switch in our brains the same way the fats and proteins do.

The Satiety Switch

In the part of our brain called the hypothalamus, there are some clusters of signal receptors.  The hypothalamus monitors the body’s energy levels and when they drop it tells us we’re hungry with a hormone called ghrelin; when it rises, it tells us to stop eating with a hormone named leptin.  It is an extremely simple and effective system…but it can be fooled by carbohydrates, an unnatural food for humans.

The Solution

Humans crave carbs because they represent cheap, easy-to-acquire energy, and are easily identified by “sweetness”.  What we could do is eliminate most carbs from our diet.  The liver makes exactly enough glucose (sugar/carbs) to run our entire body constantly from the fat and proteins that we eat.  There is no need for any carbs in a normal diet.  Our requirements vary very slightly, depending on what we’re doing, but our bodies need about 1 gram (~1/5 teaspoon) of glucose (blood sugar) every 15 minutes, or about 1,400 Kcal for an average person, per day.

But eliminating carbs is unlikely to happen because they are so integrated into our daily lives.  In fact, overeating generally is built into most First and Second World cultures.  We need to find another way to trigger that Satiety Switch, and that is where both Semaglutide and Tirzepatide come into the picture.

Most Anti-Obesity Medications (AOM) are only about 5% more effective than a placebo.  The number is statistically significant, but not very useful for most people.  Going from 157.5 lbs. to 150 may be great for swimsuit season, but the health effects are trivial.  Similarly, going from 300 to 285 is not going to make a terribly significant health impact.

Semaglutide and Tirzepatide are different than AOMs, first in that they are astonishingly more effective, and second in that they require minimal effort and no “willpower” from patients.  When you’re not “hungry” you stop eating, not by force of will, but by lack of interest in further eating.

Semaglutide

Semaglutide is a GLP-1 (Glucagon-like peptide-1) replacement.  Naturally occurring GLP-1 in our bodies lasts less than two minutes because other things work to break it down.  Semaglutide, on the other hand, has been supplemented with two amino acids to structurally reinforce the molecule so it can persist for 165-184 hours in the human body, continuing to do its job. 

This means that, unlike AOMs, this can be administered in as little as a 2.4 mg dose, once per week.  It’s easy to use, highly effective, inhibits appetite, decreases the desire for unhealthy food choices, and enhances satiety, all while modulating glucose-dependent insulin release and glucagon suppression.

In one clinical study, a daily dose of 0.4 mg (2.8 mg/week) provided a 13.8% weight reduction over 52 weeks.  If that seems slow, contrast it with the years that it took to generate 350 pounds of fat in the first place.  When combined with lifestyle changes, however, that could decrease much more quickly.  Going from 350 to 300 in a year would be a significant health benefit.  It would decrease cardiovascular stress, hypertension, and cholesterol accumulation, reduce pulmonary problems, and reduce insulin resistance.

In a study of 2.4 mg/week (single dose) 69% achieved at least a 5% weight loss; 46% at least a 10% loss, and 26% a 15% weight loss.

Tirzepatide

Like Semaglutide, Tirzepatide emulates GPL-1, but also acts as a glucose-dependent insulin-moderating polypeptide, altering insulin’s activity and release.  It has an increased effect over Semaglutide, but interestingly enough, when used in combination, has an ever greater effect.

Typically in clinical studies, it is administered as a 5, 10 or 15 mg dose.  In one 72 week study of more than 2,500 adults, the mean weight loss was 15% with the 5mg dose; 19.5% with the 10 mg dose; and 21% with a 15 mg dose.  In other words, at 15 mg, 77% lost 5% or more, 47% lost 10 % or more, and 27% lost 15% or more.

Synergy

Combining both drug therapies, specifically in diabetic patients with an urgent need to lose weight, was even more effective.  Using just 1 mg of Semaglutide, and 15 mg of Tirzepatide, 80% lost 5%, 57% lost 10% and 36% lost 15% of their body weight, or roughly 33% better than either Semaglutide or Tirzepatide alone.

Pros & Cons

Losing weight will decrease the risk of T2DM (Type-2 Diabetes Mellitus), dyslipidemia (uncontrolled, excessive, blood fats), cardiovascular disease, atherosclerosis, and more, which is a clear benefit.  Conversely, both drugs did little to modify (improve) glycemic control, decreasing the HbA1c measurement (the test used to diagnose diabetes and pre-diabetes) by only 1.5-2.3% over 68 weeks.

Adverse Events (AE) of both treatments were minor and mostly tolerable.  They came in the form of gastrointestinal distress (stomach ache/upset), nausea, and even vomiting, early in the testing and subsided.  All levels of Tirzepatide (5, 10, 15 mg) had AEs between 63.6 and 68.9%.  Semaglutide doses of 1.0-2.4 mg had AEs that ran between 64.2 and 81.8%.  Notably, those in the placebo group had AEs of 66.1-76.9%, despite receiving no medication.

We Need Fat

Males aged 18-39 should have 8-19% body fat; 40-59 should target 11-21%; over 60 should have 13-24% body fat.  Females 18-39 should have 17-32% body fat; 40-59 should be 23-33%, and those 60+ should target 24-35%.  Boys under 18 should not be more than 22% or less than 12%.  Girls in that age range should not exceed 25% or be less than 14%.

Grown or raised, we need protein and fat in our diets.  Carbohydrates are too ubiquitous to completely avoid in our society, so these treatment strategies are precisely the thing we need to reduce our food cravings for unhealthy things, stem our appetites, and make a healthy diet appetizing and satisfying in one simple step.

The Takeaway

As mentioned earlier, ghrelin and leptin signal “hungry” and “full”, respectively.  If there is dysregulation of these hormones, it can knock the body’s homeostasis out of order.  The body won’t have any way to determine if it is hungry or full, and may call for food constantly because it thinks it is starving.

This leads to all of the comorbidities or diseases mentioned above.  Ghrelin is made in the gastrointestinal tissue, and the amount created tells us when we are hungry based on our blood sugar levels and the contents of the digestive tract.  Leptin is made in the fat tissue of the body, and the amount in the bloodstream tells the body whether it needs to store more.  If they are not doing their job properly, Semaglutide and Tirzepatide can trigger the necessary effects on a sustained basis to permit safe, continuous, non-damaging, and healthy weight loss.

The existing AOMs are not up to the task of treating obesity.  These two new peptide treatments can be administered one time per week—making them quite convenient—and they both demonstrate significantly better results than currently approve AOMs.  It should also be noted that some AOMs come with risks such as thyroid or other cancers, but the need to lose weight is more urgent than that risk.  These safer alternatives can significantly improve weight loss speed and outcomes without jeopardizing other aspects of health.

Obtaining these treatments (in the U.S.) requires a prescription from your doctor.  Weight loss is an “off-label application” so most medical plans will not pay for them.  Monthly costs have been noted to range between $400 and $1,500 per month, so many are buying chemically identical generics on the internet for just a fraction of the price.

Feel free to contact us because we would love to hear from you and start you on your journey to a better healthier weight at a far more reasonable cost than you might find anywhere else.  Call us today!

References

https://www.ncbi.nlm.nih.gov/books/NBK555906/#:~:text=%5B3%5D%20Together%2C%20ghrelin%20and,affect%20the%20body%27s%20energy%20homeostasis.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8987449/.

https://www.who.int/news/item/04-03-2022-world-obesity-day-2022-accelerating-action-to-stop-obesity.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8987449/.

https://livehealthy.chron.com/healthy-body-fat-levels-based-age-3473.html

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