As we near the holidays, you have two choices:
- Set your scale back 15 lbs at midnight . . . Just before the holiday
- Come and talk to me about GLP-1 agonists
“Doc, for the first time in three years I’ve lost 10 lbs in a month . . .!”
“The constant food noise is gone from my brain . . . “
“My constant cravings are gone . . .”
I’ve heard these comments over and over in the last 3 months.
Patients following ketogenic or carnivorous diets with persistent insulin elevation will initially lose weight, but then struggle and plateaued with their weight loss. I’ve seen it for years.
When your fasting insulin stays high, the weight doesn’t want to move until you coax those fat cells to open up. This is a challenge because there are 42 different hormones that communicate between our gut, brain, pancreas and fat cells that are responsible for controlling our weight.
I hear the complaint of weight loss stalls from my severely insulin resistant and diabetic patients all the time.
The challenge is that weight doesn’t drop until the fat cells heal, then they will open up and weight loss can occur.
There are number of ways to do this. Helping the “sick fat cells” to heal occurs by maintaining a ketogenic state through carbohydrate restriction and heavy exercise, using Curcumin and decreasing the satiety signals at the gut and brain.
This is where caloric intake begins to play a role in weight management.
Semaglutide and tirzepatide are the two incretin peptides that work to help this process along. Until recently these peptide medications cost over $1000 per month to use, and if covered by your insurance, your pharmacy charges you a $250-$450 per month copay.
I’ve been using these medications in my practice with diabetic patients since 2005, nearly 18 years at the time of this writing.
They are very effective and I am a proponent of their success . . .
With a caveat.
The once weekly GLP-1 receptor agonist medications like semaglutide (Ozepic, Trulicity and Wegovy) have become very popular for good reason. Additionally the most recently approved combo GLP-1/GIP agonist tirzepatide (Monjaro or Zepbound) has skyrocketed in its use due to their weight loss and celebrity testimonials.
Prior to the availability of weekly forms of GLP-1 agonists, exanatide (Byetta and later Bydureon) and liraglutide (Victoza, Saxenda) and lixisenatide (Adlyxin) were available in a daily form.
These GLP-1 receptor agonists are non-insulin based medications approved for the treatment of diabetes type 2, and recently for weight loss, in those with elevated insulin and blood sugar who are overweight or obese.
They are usually found in the injectable form, however there is a daily oral pill form of semaglutide (Rybelsus) that was approved in 2019.
GLP-1 is an incretin hormone. This is the hormone produced by the gut when it stretches. When you eat a large meal, like Thanksgiving dinner, GLP-1 essentially tells the hypothalamus in the brain the gut is full and decreases hunger and thirst. Though they do have an insulin stimulating effect on the pancreas that also lowers blood sugar, because of the decrease in appetite and the slowing of transit time in the gut, overall insulin levels drop allowing for fat loss, especially visceral fat.
Byetta was first FDA approved in 2005 and Victoza was FDA approved in 2010.
Glucose-dependent insulinotropic polypeptide (GIP) is a second incretin released from the gut when enabling optimal levels of insulin secretion via the GIP receptor (GIPR) on β cells.
Because of this, appetite decreases, blood glucose is lowered and weight loss occurs secondarily.
Because of their popularity, they are now in short supply and manufacturers don’t think they will be able to fill the need until mid 2024.
No Drug is without Side Effects:
The following can occur in those using these medications: Abdominal and back pain, rash, itching, nausea, vomiting, slowing of gut transit time (gastroparesis), ileus (partial bowel obstruction), dizziness, heart palpitations, hoarseness, dry mouth, extreme thirst, decreased urination, shortness of breath, swelling in the face, feet, ankles or lower legs.
If you’ve had pancreatitis, gastroparesis (slow transit of the GI system) or are on dialysis, you shouldn’t use these drugs.
In animal studies GLP-1 agonists were shown to promote thyroid cell tumors, specifically these drugs should NOT be used in those with a family history of thyroid medullary cancer or multiple endocrine neoplasia type 2.
Muscle Loss with Weight Loss
The problem is that not all weight loss is considered healthy. This class of medication, although effective in reducing total body mass can be problematic if the diet is not correct. Post market, many physicians see muscle loss if adequate protein is not taken in with meals. This not so great because of the reduction of lean body mass in addition to fat mass.
Two recently published studies demonstrate that these miracle drugs are not so miraculous when looked at more closely. It should be noted that these patients were not following ketogenic or carnivorous diets. In my clinical experience, there is no muscle loss with these drugs if adequate protein is being ingested daily.
First, the STEP 1 trail conducted in 2021 looked at 140 patients under a DEXA scan for body composition and when evaluated, almost 40% of the weight loss was muscle or lean body mass. From a weight loss perspective that sucks. [Wilding JPH, et al. STEP 1 Study Group of the Once-Weekly Semaglutide in Adults with Overweight or Obesity. N Engl J Med 2021; 384:989-1002. DOI: 10.1056/NEJMoa2032183. Once-Weekly Semaglutide in Adults with Overweight or Obesity | NEJM]
In a second study, the SUSTAIN 8 trial, looking at semaglutide (Ozempic) as a diabetic treatment, the average proportion of lean body mass loss was nearly identical at around 40%, despite lower doses and less total weight loss than in the STEP 1 trial. [McCrimmon, R.J., Catarig, AM., Frias, J.P. et al. Effects of once-weekly semaglutide vs once-daily canagliflozin on body composition in type 2 diabetes: a substudy of the SUSTAIN 8 randomized controlled clinical trial. Diabetologia 63, 473–485 (2020). https://doi.org/10.1007/s00125-019-05065-8]
This can be an acceptable side effect in those with overweight and obesity challenges if you are trying to control blood sugar in a diabetic population, as these are significant risk factors for early death and vascular disease.
However, these drugs have gained huge popularity in those that are not obese.
Even those that are obese, not everyone can afford to lose significant muscle mass. Sarcopenia in older adult populations is a significant risk factor in lifespan and longevity.
Remember weight loss is not always fat loss.
I am a big fan of the GLP-1 agonists when paired with a ketogenic or carnivorous diet.
I hope this gives you a little insight into the risks and benefits of using these GLP-1 agonists and how I recommend them being used.
I’ve recently been able to locate a compounding pharmacy that can make these for my patients at 15% of that cost using the FDA approved base form of the medication, around $150 for the starting dose of semaglutide and $200 for the starting dose of tirzepatide (Note: prices subject to change based on manufacturing cost and shipping).
If you are interested in using these peptides, semaglutide or tirzepatide in conjunction with your ketogenic diet and exercise program, schedule an appointment with us today.
To Your Health & Longevity
Adam Nally, DO
References:
- Wilding JPH, et al. STEP 1 Study Group of the Once-Weekly Semaglutide in Adults with Overweight or Obesity. N Engl J Med 2021; 384:989-1002. DOI: 10.1056/NEJMoa2032183.
- McCrimmon, R.J., Catarig, AM., Frias, J.P. et al. Effects of once-weekly semaglutide vs once-daily canagliflozin on body composition in type 2 diabetes: a substudy of the SUSTAIN 8 randomised controlled clinical trial. Diabetologia 63, 473–485 (2020). https://doi.org/10.1007/s00125-019-05065-8
