An October 2023 examine1 in JAMA revealed that glucagon-like peptide-1 (GLP-1) receptor agonists prescribed for diabetes and weight reduction enhance your danger for gastrointestinal problems, together with pancreatitis, gastroparesis and bowel obstruction.
The demand for weight reduction merchandise is estimated to develop at a report compound annual development fee (CAGR) of 9.7% from 2023 to 2032.2 According to consulting agency Custom 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. Another 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 the favored GLP-1 receptor agonists is semaglutide, extra generally often known as Ozempic. Semaglutide is bought underneath two names. As Ozempic, it’s a diabetes drug and as Wegovy it’s bought in increased doses as a weight reduction drug.
The firm 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 might result in debilitating unintended effects, together with abdomen paralysis and pancreatitis. Before analyzing the outcomes of the JAMA examine, let’s take a minute to learn the way GLP-1 medicine work.
How GLP-1 Drugs Work
GLP-1 agonists are a category of remedy prescribed to handle blood sugar ranges and extra lately, to deal with weight problems.7 Most are injectable medicines and the primary on this class was authorised 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 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 Symptoms embody feeling full after beginning a meal and feeling full lengthy after consuming a meal. The commonest explanation for gastroparesis is diabetes.
In the Wegovy medical trials,9 44% of the contributors taking the drug skilled nausea, 24% vomited and 20% had belly 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 had been related to “delay in gastric emptying of solids,”10 and the longer meals sat within the abdomen, the better 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 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. But that is not the one drug impact.
Is Weight Loss Worth Pancreatitis, Gastroparesis and Ileus?
Injected GLP-1 agonists amplify the impact of the physique’s GLP-1 and gradual digestion, which helps hold individuals feeling full longer.11 In 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 danger 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 contributors who had been new customers of one of many two GLP-1 agonists semaglutide or liraglutide.
They in contrast the outcomes in opposition to bupropion-naltrexone. Within 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 danger of pancreatitis, bowel obstruction and gastroparesis, however not biliary illness. When sufferers with hyperlipidemia had been faraway from the evaluation it didn’t change the outcomes.
Science Alert notes that whereas the rise in danger 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 growing these well being situations.
“When you have millions of people using these drugs, you know, a 1% risk still translates to many people who may experience these events,” stated lead examine writer Mahyar Etminan, Pharm.D, an epidemiologist on the University of British Columbia, chatting with CNN.13
As Forbes reported,14 on September 22, 2023, only one month earlier than the featured examine was printed, the FDA added “ileus” to the checklist 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 may end up in an intestinal blockage.
It’s not shocking that if GLP-1 agonists gradual gastric emptying velocity, they might additionally gradual the motion within the small intestines, thus rising the chance of ileus and intestinal blockage.
GLP-1 Receptor Agonists Trigger Intestinal Changes
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 fee 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 could enhance intestinal size and villus top. The villi are the hair-like projections contained in the small intestines that assist take up vitamins. Researchers clarify this could significantly have an effect on intestinal perform, rising the obstruction danger as a result of “… the small gut could turn into as inelastic and fibrotic as a unfastened spring, resulting in long-term higher intestinal obstruction …”
To date, these modifications 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 medicine earlier than elective surgical procedure.16 They counsel sufferers cease all GLP-1 receptor agonists to cut back the chance of issues related to regurgitating meals even for those who fasted appropriately.
The ASA recommends not taking the remedy for at some point for individuals who take it day by day to 1 week for individuals who take a weekly injection, and delaying the process if signs of delayed gastric emptying are current. The probability of getting a full abdomen and the related danger 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.
Long-Term Results Are Not What You Might Expect
It can take a number of months to achieve your personalised goal dose whereas managing the unintended effects of the drug. In one New England Journal of Medicine 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 pair of.4% physique weight reduction within the placebo group.
In a second examine18 printed in Nature Medicine, a cohort of adults with weight problems or obese and one associated comorbidity, had 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.
While 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 often 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 keep up enhancements in weight and well being.”
Most research additionally recorded important unintended effects with short-term therapy20 that brought on contributors to withdraw from the research.21 Serious and customary unintended effects of semaglutide22 embody nervousness, confusion, melancholy, bother respiratory, nightmares, seizures and slurred speech.
Is There a Natural Option for ‘Skinny Injections?’
In the Energy Balance Podcast above, unbiased well being researchers Jay Feldman and Mike Fave clarify why consuming an excessive amount of and exercising too little just isn’t the explanation for weight achieve. Jay is without doubt one of the finest 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 is my sturdy perception that we’ll by no means see the “miracle remedy” medicine for weight reduction in our lifetime. Using medicine to shed extra pounds might result in everlasting, debilitating well being issues and it’s seemingly you’ll regain the load for those who ever cease taking them, as was demonstrated by the pharmaceutical firm promoting Wegovy and Ozempic.
There are presently higher options to handle the basic cause individuals achieve weight — insulin resistance secondary to mitochondrial dysfunction from extra reductive stress. Excess linoleic acid (LA) from seed oils is the first explanation for mitochondrial reductive stress. Some of the highest methods to shed extra pounds and enhance your well being embody:
• Reduce your consumption of seed oils whereas rising wholesome fat — Consuming an excessive amount of LA is the first issue driving the obese 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.
Consider chopping LA right down to beneath 5 grams per day, which is near what our ancestors used to devour earlier than power well being situations, together with weight problems, turned widespread. The quantity is healthier outlined as a share of day by day energy. LA must be lower than 2% of your day by day energy. You can observe this by rigorously coming into your meals knowledge into Cronometer.
• Avoid almost all ultraprocessed meals, quick meals and restaurant meals — Virtually all include seed oils. The simplest way to do that is to arrange most of your meals at dwelling so you recognize 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. When you eat each few hours for months, years or many years, your physique forgets learn how to burn fats as gas. Most individuals who observe TRE restrict the time they devour meals to eight to 10 hours or much less on most days of every week.
• Consider berberine to assist regulate blood sugar and insulin sensitivity — As I’ve reported earlier than, berberine is named “nature’s Ozempic” and is understood to assist stop diarrhea, decrease the chance of leaky intestine, nourish useful microbes and enhance signs of fatty liver illness.
Other useful results exterior the gastrointestinal tract embody easing signs of tension and melancholy, enhancing signs of PTSD in an animal mannequin and easing signs of opioid withdrawal.