We established a theoretical model for how the modulation of GLP-1 agonists via increased serotonergic activity at the 5-HT2C receptor may have an associated negative effect on sexual desire. We then applied a biopsychosocial framework to highlight why this effect may be overlooked by both GLP-1-treated patients and clinicians. Although the serotonergic pathway may create a physiological decrease in sexual desire for patients taking GLP-1 agonists, the biopsychosocial factors discussed propose a potential mechanism by which these adverse effects are masked. In other words, we postulate that the negative influence of GLP-1 agonism on sexual desire, mediated by serotonergic pathways, as well as undesirable facial effects (“Ozempic Face”) and increased SHBG, etc., are offset by the positive influences on sexual desire such as increased total testosterone, improved vascular reactivity, and a more positive mood.
Resolution of steatohepatitis without worsening of fibrosis occurred in 62.9% of the 534 patients in the semaglutide group and in 34.3% of the 266 patients in the placebo group (estimated difference, 28.7 percentage points; 95% confidence interval [CI], 21.1 to 36.2; P<0.001). A reduction in liver fibrosis without worsening of steatohepatitis was reported in 36.8% of the patients in the semaglutide group and in 22.4% of those in the placebo group
Old semaglutide still has some tricks up its sleeves
I think there is a general issue with the loss of lean weight mass with fat going. It needs a proper resolution rather than ending up with lots of thin really frail older people.
Mazdutide is a product of China, and the focus of this GLP1 RA has been tailored to the challenges of obesity and cardiometabolic disease in the Chinese population
Our trial participants were relatively young with a high prevalence of weight-
related cardiometabolic diseases, most notably dyslipidemia (in 62.3%), MAFLD (in 48.9%), hyper-
uricemia (in 40.2%), and hypertension (in 22.8%). Our results are consistent with results of a re-
cent study involving young Chinese adults, which showed an alarmingly high prevalence of the
same weight-related cardiometabolic conditions.
Our trial population differs from that of other trials to date. China adopted lower BMI cutoffs
for overweight and obesity than those used by the World Health Organization.
Some nice results:
In participants with liver steatosis, mazdutide treatment for 48 weeks appeared to be associ-
ated with a greater reduction in liver-fat content than placebo, and more participants who received
mazdutide had relative reductions of 30% and 50% in liver-fat content and a liver-fat content of
less than 5% at week 48 than those who received placebo
This reduction in liver fat content is probably due to GCGR
The potential and unique metabolic effects of mazdutide that differentiate it from GLP-1 recep-
tor agonists and other GLP-1–based dual agonists appear to stem from glucagon agonism. Al-
though a head-to-head comparison of mazdutide with GLP-1 receptor agonists is important for a
firm conclusion, we speculate that the seemingly more-pronounced overall improvements in lipid
metabolism, such as reductions in triglyceride and alanine aminotransferase levels and most
notably in liver-fat content, may be attributable to glucagon-driven lipid oxidation in the liver
and in adipose tissue.12 These observations may be important, given the high prevalence of fatty
liver and dyslipidemia among Chinese adults with obesity or overweight.
Not disagreeing, but this is not an issue specific to GLP1 medication, and the solution is simple: resistance training 2-3 times a week. But we all know simple doesn’t mean easy.
DEXA scans themselves has limitations to keep in mind:
cannot distinguish between different muscle groups (e.g., deep vs. superficial muscles) or identify intramuscular fat
DEXA relies on tissue density, so changes in hydration can artificially alter lean mass readings.
In some cases, it classifies water or glycogen stores as lean mass. It’s important to keep in mind that some percentage of weight loss is water weight loss, which impacts lean mass readings negatively. So your muscle tissues has less water in them, but you haven’t actually lost muscle weight
DEXA only tells you about lean mass, not actual muscle mass. Lean mass includes water, tendons, bones.
The gold standard is MRI, and hopefully there will be studies where we can get more precise readings on fat vs muscle mass loss.
Hey Steve! I saw a couple of posts where you commented about peptides. I’m really interested in your journey and learning more about your suppliers. Do you think we can connect?
A study recently published in Frontiers of Nutrition found that individuals on GLP-1 therapy had insufficient intakes of key nutrients like fiber, calcium, iron, magnesium, potassium and vitamins A, C, D and E.
Most patients who are prescribed GLP-1 receptor agonists do not receive appropriate nutritional counseling, despite the known benefits, so the advisory “seeks to fill that gap with practical, interdisciplinary guidance for implementation in clinical practice,” according to a press release.
The advisory stresses the importance of:
careful baseline nutritional assessment;
maximizing weight reduction with a good diet;
patient-centered initiation of therapy;
personalized diets that are minimally processed and nutrient-dense;
lean mass preservation via strength training and adequate protein intake;
gastrointestinal adverse effect management;
micronutrient deficiency prevention; and
promoting other positive lifestyle changes in several areas — like sleep, exercise, substance use, mental stress and social connections — to ensure long-term success.
This is not rocket science thankfully, and it’s been done before. Before GLP1 therapy, people used to lose massive amounts of weight through bariatric surgery. The after care program, and concerns from those surgeries look very similar to what’s been proposed here for GLP1 therapies. It’s well-known that these patients have to be on multivitamins, multiminerals, and in some cases add extra iron, calcium, magnesium, zinc, etc.
Analysis included 8284 reports for liraglutide (n = 3022), 14,435 for semaglutide (n = 4233), and 15,597 for tirzepatide (n = 5722). Significant signals were identified only for semaglutide in both depression (ROR, 1.87; 95 % CI, 1.60–2.20) and suicide/self-injury events (ROR, 1.73; 95 % CI, 1.46–2.04). Effects were consistent across sex groups but most pronounced in ages 18–64. Post-weight management approval saw increased reporting, particularly in European and North American regions. Tirzepatide showed significantly lower mortality rates (0.26 %) compared to other agents.
Findings identified significant depression and suicidality signals with semaglutide in weight management. For patients requiring weight reduction therapy, particularly those with psychiatric comorbidities, tirzepatide may represent a more appropriate choice based on its superior safety profile.
Sadly, the large majority of people on GLP1’s are too lazy to work out and still eat junk. They just eat much less junk as a result of their appetites being suppressed, hence the weight loss. So given the fact they’re not eating much but are still eating junk whenever they do, they’re more likely to be deficient in just about everything. These people need a quality multivitamin more than anyone, but few are taking one.
On the other hand, if someone uses a GLP1 in addition to a healthy diet and good exercise program, they should be able to avoid deficiencies.
Educatre doctors to promote generic multivitamins to their patients, problem solved. If something is as easy as taking a pill most people are willing to do it.
I thought people on GLP-1 agonists shifted to more high protein and high fiber meals, there’s even food products made for people on GLP-1 agonists. Are you sure about this?
They don’t even have to eat junk, they would still be missing nutrients since they eat less. Bariatric surgery patients ate prescribed all kinds of supplements because of that: calcium, fiber, multivitamins, etc . This is no different in my opinion.
That would mirror my observations too : less junk food overall because they either lose the taste for it, or they get nauseated by it, or worse GI symptoms after consuming it.
It does alter taste and desire. They might try to eat foods they intellectually consider healthier, and consume smaller portions. If they don’t consider consuming higher protein foods they won’t do it. It’s an education issue.
Just from my own experience of the people I speak with, it sounds like most people using them don’t have good lifestyle habits. There are exceptions though.
