An October 2023 examine1 in JAMA revealed that glucagon-like peptide-1 (GLP-1) receptor agonists prescribed for diabetes and weight reduction improve your threat for gastrointestinal issues, together with pancreatitis, gastroparesis and bowel obstruction.
The demand for weight reduction merchandise is estimated to develop at a report compound annual progress charge (CAGR) of 9.7% from 2023 to 2032.2 Based on consulting agency Customized Market Insights, the worth of the U.S. weight reduction market in 2022 was $135.7 billion and is forecasted to succeed in $305.3 billion by 2030. One other estimate3 initiatives the U.S. weight reduction market will attain $405.4 billion by 2030.
The demand for prescription weight reduction medicines has additionally skyrocketed, with prescriptions rising 2,082% from 2019 to 2022.4 One of many common GLP-1 receptor agonists is semaglutide, extra generally generally known as Ozempic. Semaglutide is bought underneath two names. As Ozempic, it’s a diabetes drug and as Wegovy it’s bought in larger doses as a weight reduction drug.
The corporate boasts a weight lack of 14.9% in adults with weight problems,5 however this comes at a steep monetary and bodily value. The drug prices greater than $1,000 every month,6 and may result in debilitating unintended effects, together with abdomen paralysis and pancreatitis. Earlier than inspecting the outcomes of the JAMA examine, let’s take a minute to learn the way GLP-1 medication work.
How GLP-1 Medication Work
GLP-1 agonists are a category of medicine prescribed to handle blood sugar ranges and extra not too long ago, to deal with weight problems.7 Most are injectable medicines and the primary on this class was accepted by the FDA in 2005. Your physique naturally makes the GLP-1 hormone within the small intestines, which slows digestion, will increase satiety, blocks the secretion of glucagon and triggers the pancreas to launch insulin.
GLP-1 agonists mimic the hormone, so the medicine binds to the receptor and triggers these similar results. Delayed gastric emptying is the hallmark of gastroparesis, in which there’s a delay of meals transferring from the abdomen to the small intestines and not using a blockage.8 Signs embrace feeling full after beginning a meal and feeling full lengthy after consuming a meal. The most typical reason behind gastroparesis is diabetes.
Within the Wegovy medical trials,9 44% of the contributors taking the drug skilled nausea, 24% vomited and 20% had stomach ache. Mayo Clinic researchers additionally seemed on the results of liraglutide, one other GLP-1 receptor agonist, in adults with weight problems. They discovered the drug’s weight reduction results have been related to “delay in gastric emptying of solids,”10 and the longer meals sat within the abdomen, the better the load loss results grew to become.
In a placebo group, the abdomen usually emptied inside 4 minutes however after 5 weeks on the drug, the median gastric emptying time was 70 minutes, and as much as 151 minutes in some contributors. By 16 weeks, the gastric emptying time had decreased to 30.5 minutes, which was nonetheless longer than the placebo group. By dramatically slowing digestion, contributors felt full longer and did not eat as a lot. However that is not the one drug impact.
Is Weight Loss Price Pancreatitis, Gastroparesis and Ileus?
Injected GLP-1 agonists amplify the impact of the physique’s GLP-1 and sluggish digestion, which helps preserve individuals feeling full longer.11 Within the featured examine12 researchers sought to guage the chance of gastrointestinal antagonistic occasions in GLP-1 agonists used within the therapy of diabetes and off label for weight reduction.
The researchers acknowledged that previous research had discovered these with diabetes had an underlying elevated threat for pancreatitis, bowel obstruction and gastroparesis. They took a random pattern of sufferers from 2006 to 2020 utilizing a well being claims database that captures 93% of outpatient prescriptions and ICD-9 and ICD-10 prognosis codes. They selected contributors who have been new customers of one of many two GLP-1 agonists semaglutide or liraglutide.
They in contrast the outcomes towards bupropion-naltrexone. Inside the cohort that they had 4,144 contributors taking liraglutide, 613 taking semaglutide and 654 taking bupropion-naltrexone. They discovered these taking GLP-1 agonists had an elevated threat of pancreatitis, bowel obstruction and gastroparesis, however not biliary illness. When sufferers with hyperlipidemia have been faraway from the evaluation it didn’t change the outcomes.
Science Alert notes that whereas the rise in threat is comparatively small, contemplating the rising variety of individuals utilizing the medicines, it nonetheless represents a fourfold improve within the variety of people who find themselves in danger for growing these well being circumstances.
“When you might have tens of millions of individuals utilizing these medication, you realize, a 1% threat nonetheless interprets to many individuals who could expertise these occasions,” stated lead examine writer Mahyar Etminan, Pharm.D, an epidemiologist on the College of British Columbia, chatting with CNN.13
As Forbes reported,14 on September 22, 2023, only one month earlier than the featured examine was revealed, the FDA added “ileus” to the listing of potential antagonistic occasions on the Ozempic label. Two different GLP-1 receptor agonists, Mounjaro and Wegovy, already had warnings about ileus, which is a well being situation that can lead to an intestinal blockage.
It’s not stunning that if GLP-1 agonists sluggish gastric emptying pace, they might additionally sluggish the motion within the small intestines, thus growing the chance of ileus and intestinal blockage.
GLP-1 Receptor Agonists Set off Intestinal Adjustments
In a 2023 letter to the editor of Acta Pharmaceutica,15 the writers recount the outcomes of a examine in diabetic sufferers who used GLP-1 receptor agonists and located a 3.5-fold improve within the charge of intestinal obstruction in a examine of 25,617 individuals. The medication additionally elevated the size and weight of the small intestines in animal research.
In people, they might improve intestinal size and villus peak. The villi are the hair-like projections contained in the small intestines that assist take in vitamins. Researchers clarify this could severely have an effect on intestinal operate, growing the obstruction threat as a result of “… the small gut could change into as inelastic and fibrotic as a free spring, resulting in long-term higher intestinal obstruction …”
To this point, these adjustments haven’t been measured within the human intestine, seemingly as a result of it is tough to measure the size of the small intestines. The delay in abdomen emptying led the American Society of Anesthesiologists to launch a warning for these taking GLP-1 medication earlier than elective surgical procedure.16 They counsel sufferers cease all GLP-1 receptor agonists to scale back the chance of problems related to regurgitating meals even if you happen to fasted appropriately.
The ASA recommends not taking the medicine for someday for individuals who take it day by day to at least one week for individuals who take a weekly injection, and delaying the process if signs of delayed gastric emptying are current. The chance of getting a full abdomen and the related threat with anesthesia is so excessive that the ASA suggests utilizing ultrasound to guage the abdomen contents earlier than surgical procedure if the affected person didn’t withhold the drug.
Lengthy-Time period Outcomes Are Not What You May Anticipate
It may well take just a few months to succeed in your customized goal dose whereas managing the unintended effects of the drug. In a single New England Journal of Medication examine,17 researchers administered 2.4 mg of semaglutide in a double-blind trial involving 1,961 adults with a physique mass index of 30 or better. The change in physique weight from baseline at 68 weeks was a lack of 14.9% within the therapy group and a couple of.4% physique weight reduction within the placebo group.
In a second examine18 revealed in Nature Medication, a cohort of adults with weight problems or chubby and one associated comorbidity, have been administered 2.4 mg of semaglutide subcutaneously for 104 weeks. In that point, the intervention group misplaced 15.2% of their physique weight versus 2.6% physique weight reduction in these taking a placebo.
Whereas these outcomes appear encouraging, it is necessary to notice that the pharmaceutical firm designed semaglutide as a chronic-use drug. In different phrases, it’s meant for use repeatedly over a protracted interval. A examine19 funded by Novo Nordisk discovered that one 12 months after withdrawing the drug, contributors regained two-thirds of the load misplaced and the researchers concluded that “ongoing therapy is required to take care of enhancements in weight and well being.”
Most research additionally recorded vital unintended effects with short-term therapy20 that prompted contributors to withdraw from the research.21 Critical and customary unintended effects of semaglutide22 embrace nervousness, confusion, despair, bother respiratory, nightmares, seizures and slurred speech.
Is There a Pure Choice for ‘Skinny Injections?’
Within the Power Steadiness Podcast above, unbiased well being researchers Jay Feldman and Mike Fave clarify why consuming an excessive amount of and exercising too little is just not the explanation for weight acquire. Jay is without doubt one of the greatest academics of the Bioenergetic view of well being. I might strongly encourage you to hearken to his YouTube channel, however watch the oldest ones first so you will get grounded within the fundamentals.
It’s my sturdy perception that we’ll by no means see the “miracle remedy” medication for weight reduction in our lifetime. Utilizing medication to shed extra pounds might result in everlasting, debilitating well being issues and it’s seemingly you’ll regain the load if you happen to ever cease taking them, as was demonstrated by the pharmaceutical firm promoting Wegovy and Ozempic.
There are presently higher options to handle the elemental cause individuals acquire weight — insulin resistance secondary to mitochondrial dysfunction from extra reductive stress. Extra linoleic acid (LA) from seed oils is the first reason behind mitochondrial reductive stress. A number of the prime methods to shed extra pounds and enhance your well being embrace:
• Scale back your consumption of seed oils whereas growing wholesome fat — Consuming an excessive amount of LA is the first issue driving the chubby and weight problems epidemics. LA is a sort of omega-6 fats present in seed oils like soybean, cottonseed, sunflower, rapeseed (canola), corn and safflower.
Think about slicing LA right down to under 5 grams per day, which is near what our ancestors used to eat earlier than persistent well being circumstances, together with weight problems, grew to become widespread. The quantity is best outlined as a share of day by day energy. LA ought to be lower than 2% of your day by day energy. You possibly can monitor this by rigorously coming into your meals information into Cronometer.
• Keep away from practically all ultraprocessed meals, quick meals and restaurant meals — Nearly all include seed oils. The best means to do that is to arrange most of your meals at house so you realize what you’re consuming.
• Use time-restricted consuming (TRE) — Our ancestors didn’t have entry to meals 24/7, so our genetics are optimized to having meals at variable intervals, not each few hours. Once you eat each few hours for months, years or a long time, your physique forgets the best way to burn fats as gas. Most individuals who observe TRE restrict the time they eat meals to eight to 10 hours or much less on most days of every week.
• Think about berberine to assist regulate blood sugar and insulin sensitivity — As I’ve reported earlier than, berberine is known as “nature’s Ozempic” and is thought to assist forestall diarrhea, decrease the chance of leaky intestine, nourish helpful microbes and enhance signs of fatty liver illness.
Different helpful results outdoors the gastrointestinal tract embrace easing signs of tension and despair, bettering signs of PTSD in an animal mannequin and easing signs of opioid withdrawal.
