An October 2023 examine1 in JAMA revealed that glucagon-like peptide-1 (GLP-1) receptor agonists prescribed for diabetes and weight reduction enhance your threat for gastrointestinal issues, together with pancreatitis, gastroparesis and bowel obstruction.
The demand for weight reduction merchandise is estimated to develop at a document compound annual development price (CAGR) of 9.7% from 2023 to 2032.2 In keeping with consulting agency Customized Market Insights, the worth of the U.S. weight reduction market in 2022 was $135.7 billion and is forecasted to achieve $305.3 billion by 2030. One other estimate3 tasks 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 offered underneath two names. As Ozempic, it’s a diabetes drug and as Wegovy it’s offered in greater 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 unwanted side effects, together with abdomen paralysis and pancreatitis. Earlier than analyzing the outcomes of the JAMA examine, let’s take a minute to find out how GLP-1 medicine work.
How GLP-1 Medication Work
GLP-1 agonists are a category of remedy prescribed to handle blood sugar ranges and extra just lately, to deal with weight problems.7 Most are injectable medicines and the primary on this class was permitted 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 remedy binds to the receptor and triggers these identical results. Delayed gastric emptying is the hallmark of gastroparesis, in which there’s a delay of meals shifting 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 explanation for gastroparesis is diabetes.
Within the Wegovy medical trials,9 44% of the members taking the drug skilled nausea, 24% vomited and 20% had stomach ache. Mayo Clinic researchers additionally regarded 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 higher the load loss results turned.
In a placebo group, the abdomen sometimes 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 members. 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, members 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 gradual 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 analysis codes. They selected members who have been new customers of one of many two GLP-1 agonists semaglutide or liraglutide.
They in contrast the outcomes in opposition to bupropion-naltrexone. Inside the cohort they’d 4,144 members 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 enhance within the variety of people who find themselves in danger for creating these well being situations.
“When you’ve got tens of millions of individuals utilizing these medicine, you understand, a 1% threat nonetheless interprets to many individuals who could expertise these occasions,” mentioned lead examine writer Mahyar Etminan, Pharm.D, an epidemiologist on the College of British Columbia, talking to 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 doable 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 gradual gastric emptying pace, they might additionally gradual 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 enhance within the price of intestinal obstruction in a examine of 25,617 individuals. The medicine additionally elevated the size and weight of the small intestines in animal research.
In people, they might enhance intestinal size and villus top. 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 perform, growing the obstruction threat as a result of “… the small gut could change into as inelastic and fibrotic as a unfastened spring, resulting in long-term higher intestinal obstruction …”
So far, these modifications haven’t been measured within the human intestine, possible as a result of it is troublesome 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 medicine earlier than elective surgical procedure.16 They recommend sufferers cease all GLP-1 receptor agonists to scale back the chance of issues related to regurgitating meals even in the event you fasted appropriately.
The ASA recommends not taking the remedy for at some point for many who take it day by day to at least one week for many 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 Would possibly Count on
It could actually take just a few months to achieve your customized goal dose whereas managing the unwanted side 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 higher. 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 vital to notice that the pharmaceutical firm designed semaglutide as a chronic-use drug. In different phrases, it’s meant for use recurrently over a protracted interval. A examine19 funded by Novo Nordisk discovered that one yr after withdrawing the drug, members 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 important unwanted side effects with short-term therapy20 that induced members to withdraw from the research.21 Severe and customary unwanted side effects of semaglutide22 embrace anxiousness, confusion, despair, bother respiratory, nightmares, seizures and slurred speech.
Is There a Pure Possibility for ‘Skinny Injections?’
Within the Power Stability Podcast above, unbiased well being researchers Jay Feldman and Mike Fave clarify why consuming an excessive amount of and exercising too little isn’t the rationale for weight achieve. Jay is among 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 may get grounded within the fundamentals.
It’s my robust perception that we are going to by no means see the “miracle treatment” medicine for weight reduction in our lifetime. Utilizing medicine to shed extra pounds may result in everlasting, debilitating well being issues and it’s possible you’ll regain the load in the event you ever cease taking them, as was demonstrated by the pharmaceutical firm promoting Wegovy and Ozempic.
There are presently higher options to deal with the basic purpose individuals achieve weight — insulin resistance secondary to mitochondrial dysfunction from extra reductive stress. Extra linoleic acid (LA) from seed oils is the first explanation for mitochondrial reductive stress. A number of the prime methods to shed extra pounds and enhance your well being embrace:
• Cut 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.
Take into account reducing LA all the way down to beneath 5 grams per day, which is near what our ancestors used to eat earlier than continual well being situations, together with weight problems, turned widespread. The quantity is healthier outlined as a proportion of day by day energy. LA needs to be lower than 2% of your day by day energy. You may observe this by fastidiously getting into your meals knowledge into Cronometer.
• Keep away from almost all ultraprocessed meals, quick meals and restaurant meals — Just about all include seed oils. The simplest approach to do that is to organize most of your meals at dwelling so you understand 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. If you eat each few hours for months, years or a long time, your physique forgets find out how to burn fats as gasoline. Most individuals who apply TRE restrict the time they eat meals to eight to 10 hours or much less on most days of every week.
• Take into account 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 stop diarrhea, decrease the chance of leaky intestine, nourish useful microbes and enhance signs of fatty liver illness.
Different useful 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.
