Intermittent (oral) Rybelsus / Semaglutide use in healthy individuals?

Effects of Semaglutide on Chronic Kidney Disease in Patients with Type 2 Diabetes (2024)

Among the 3533 participants who underwent randomization (1767 in the semaglutide group and 1766 in the placebo group), median follow-up was 3.4 years, after early trial cessation was recommended at a prespecified interim analysis. The risk of a primary-outcome event was 24% lower in the semaglutide group than in the placebo group (331 vs. 410 first events; hazard ratio, 0.76; 95% confidence interval [CI], 0.66 to 0.88; P=0.0003). Results were similar for a composite of the kidney-specific components of the primary outcome (hazard ratio, 0.79; 95% CI, 0.66 to 0.94) and for death from cardiovascular causes (hazard ratio, 0.71; 95% CI, 0.56 to 0.89). The results for all confirmatory secondary outcomes favored semaglutide: the mean annual eGFR slope was less steep (indicating a slower decrease) by 1.16 ml per minute per 1.73 m2 in the semaglutide group (P<0.001), the risk of major cardiovascular events 18% lower (hazard ratio, 0.82; 95% CI, 0.68 to 0.98; P=0.029), and the risk of death from any cause 20% lower (hazard ratio, 0.80; 95% CI, 0.67 to 0.95, P=0.01). Serious adverse events were reported in a lower percentage of participants in the semaglutide group than in the placebo group (49.6% vs. 53.8%).

https://www.nejm.org/doi/full/10.1056/NEJMoa2403347

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Semaglutide Significantly Improves Chronic Kidney Disease

“The four pillars are now a renin-angiotensin-aldosterone system (RAAS) blocker, sodium-glucose cotransporter-2 (SGLT2) inhibitors, finerenone, and semaglutide,” said study co-author Katherine R. Tuttle, MD, who is a professor of medicine, Nephrology Division and Kidney Research Institute, at the University of Washington, Seattle, while presenting the findings.
About 15% were receiving an SGLT2 inhibitor, reflecting the time period when enrollment occurred (before increased use of the drugs).
Also providing comment for Medscape Medical News, Alberto Ortiz, MD, PhD, chief of nephrology and Hypertension Renal Unit, Health Research Institute of the Jiménez Díaz Foundation, Madrid, Spain, noted caveats, including the early termination of the trial and that few patients were taking an SGLT2 inhibitor.
“The number of participants on SGLT2 inhibitors was low and results were nonconclusive for this reason,” he said. Therefore, “this trial does not answer the question of whether semaglutide adds benefit for the primary endpoint for patients who are already on the standard of care, ie, SGLT2 inhibitors.”
The issue was also the first to be raised during the question and answer session, with one audience member asserting that regulatory authorities will argue that SGLT2 inhibitors should be the comparative treatment for GLP-1 receptor agonists.
Perkovic agreed that because of the trial’s timing, the proportion of patients taking an SGLT2 inhibitor was “relatively modest.” However, he added, “I think one of the assumptions is that we have to either choose SGLT2 inhibitors or GLP-1 receptor agonists, and I would challenge that.”
“I think the question is: What benefit do we get when we prescribe [the treatments] in combination? [Ongoing research] is looking at that issue of whether the effects are additive, and we believe they are,” he said.

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Do you live in Canada? Curious if you had an issue shipping to US?

The semaglutide weight-loss miracle has a dark side: As desperate patients contend with shortages and sky-high prices, a world of criminals and con artists are filling the void with life-threatening fakes. Katherine Eban investigates our alarmingly active pharmaceutical underground.

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The plot of the South Park special episode about Ozempic is partly about ordering the powder from India and creating their own injectables. Something similar is happening here it seems, with some fraud in the mix.

Counterfeit pen with insulin is extremely dangerous, these criminals are extremely immoral.

European investigators tracing the origin of the counterfeit pens sold by the plastic surgeon followed the chain of custody through a web of distributors in Austria, Germany, and the UK and back to an all-too-familiar home base: Turkey. Specifically, an exporter in Ankara named AUB Healthcare was identified as being a conduit for the counterfeits.

Turkish Ozempic not good (in fact any black market ozempic)?

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Lipid profile changes induced by glucagon-like peptide-1 receptor agonists in patients with type 2 diabetes: a systematic review and network meta-analysis 2024

The glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 dual agonist showed significant differences in LDL-C (range of mean differences: −11.61 to −6.77%p), triglycerides (−19.94 to −13.31%p), and T-CHO (−7.94 to −5.09%p) levels compared to placebo, insulin, and sodium-glucose co-transporter 2 (SGLT2) inhibitors.
The GLP-1 agonist significantly reduced T-CHO (−5.20%p; −6.39%p) and LDL-C (−4.32%p; −8.17%p) levels compared to placebo and SGLT2 inhibitors, respectively.

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As @Rapasailor said above CanShipMeds can’t get Ozempic, it is pseudo banned in Canada I gather. AgelessRX has it available from a compound pharmacy for $240/mo. I may try for a short spell to help get my BMI just right and my 1.19lbs of visceral fat to zero.

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Ended up ordering OZ from Ageless. Got it yesterday and did my first dose today. .25mg subcon injection. Easy. I have done peptides this way before so it was natural. Ageless has good videos for those that are not comfortable with self injections. I’ll report back on sides, experience, and results. Plan to do another DexaScan in 3 months to see the specifics.

Just FYI…I saw a TV ad that Hims now offers compounded Semaglutide. It ain’t cheap at a listed price of $199/month but maybe if you talked with their doc, you could do a lower maintenance dose.
I’m sure other telemedicine places will start offering it as production ramps up.

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My wife has an online appt to try HenryMeds new compounded oral tirzepatide (supposedly absorbed via capillaries under tongue). I’ll report results (if any) after she’s tried it.

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Ozempic’s U.S. markup

A Wegovy prescription costs about $1,349 per month in the U.S., while it costs just $140 in Germany and $92 in the U.K. Novo Nordisk’s Ozempic carries similar markups.

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The Chinese bootleggers are now turning a profit making Tirzepatide for $0.80/mg, not a typo. That’s shipped, with 3rd party arranged and executed purity testing. The quality is high and the competition is intense.

I don’t pay attention to semaglutide, but it has always been even cheaper.

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Semaglutide for the prevention of atrial fibrillation: A systematic review and meta-analysis 2024

Twenty-one trials comprising 25957 patients were included. In the overall pooled analysis, semaglutide decreased AF occurrence compared to control drugs (RR 0.70, 95 % CI 0.52–0.95). This result was consistent in trials using other antihyperglycemic medications as controls (RR 0.43, 95 % CI 0.21–0.89), but not in placebo-controlled trials (RR 0.77, 95 % CI 0.56–1.07). The outcome was favorable for patients with T2DM (RR 0.71, 95 % CI 0.52–0.97), but not for patients with overweight or obesity (RR 0.56, 95 % CI 0.18–1.73). Results varied by type of semaglutide, with oral semaglutide showing an RR of 0.49 (95 % CI 0.25–0.97) and subcutaneous semaglutide showing an RR of 0.77 (95 % CI 0.55–1.07).

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I have been on OZ (compound pharmacy) .25mg for three weeks now. Here are my thoughts. Day 1 and to a lesser extent Day 2 I feel more tired than usual. I also feel some general GI uneasiness. Higher acid content, more burping and a little nauseas. For meals I feel fuller more quickly and overall less hungry. By day 3 I am pretty normal and by Day 5 hungry again. After 3 weeks I am about flat weight-wise and maybe even up a pound which is kinda weird. I realize .25 is a low dose and titrating my system to get used to it. Hoping the move to .5mg has a bigger effect on the scale/visceral fat otherwise I will stop. Juice isn’t worth the squeeze. More to follow.

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Has anyone measured their fasting serum insulin before/after semaglutide?

This 2022 paper (Semaglutide improves cardiometabolic risk factors in adults
with overweight or obesity: STEP 1 and 4 exploratory analyses
) found a significant reduction in insulin with semaglutide vs placebo (in “people with overweight/obesity without diabetes”).

In STEP 1, reductions in waist circumference, SBP, DBP, FPG, fasting serum insulin, lipids and HOMA‐IR were greater with semaglutide versus placebo (p ≤ .001).

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Update: wife and I both had ZERO effect from the HenryMeds.com oral tirzepatide, so whatever sublingual formulation they’re using from their compounding pharmacy appears to be junk (unabsorbable, assuming it actually contains tirzepatide as advertised).

At first we thought we were somehow getting appetite suppression with no side effects, but then we went to a 4th of July party and quickly realized that it had all been a placebo. Thankfully at least HM has a 30 day money back guarantee, so let’s hope they honor it.

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“The practitioner steered me toward the injectable version of the medication instead of the pill version that Henry offers, noting that it had more evidence of efficacy.”

So even they admit it’s junk

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