Semaglutide

[fasttwitch]

If you need to kill your appetite to drop a little weight holy cow try semaglutide. It makes phentermine obsolete in my opinion. Half a mg to start and I’m lucky to get more than a handful of food down. It’s super important that you eat very clean healthy food also because it will give you terrible persistent indigestion if not. Id start with a lower dose if I was advising someone I dealt with nausea the first night. Once a week is enough after day 2 it kicks in hard and goes strong for the week. Anyone else try it?

My wife is running this. She has dropped 17 lbs in 2 months without any effort. She does try to eat right. But she gets full before the entre. So far, no side effects for her.

 

[Wilson6]

What is the dosage protocol for Retatrutide?

The lower effective dose seems to be total of 1 or 2 mg/wk without GLP-1 GI sides but still effective. Starting 0.25 mg twice a week, then slowly ramping up to working dose. First ramp can be a couple weeks of there is no effect at 0.25 mg/2 x/wk, then minimum 4 weeks. The studies go much higher per week than this but clients using RETA find that 2 mg esp when combined with an androgen and/or GH is plenty for a synergistic effect and no GI sides. The effects are more subtle and take time, but RETA seems to be much better than any of the other GLP-1s out there. I would think though, at a high enough dose it will cause GLP-1 sides

 

[Kluso]

Just doing once a week. I should have started at 1/4 mg dose not a half. I would bet 1/4 mg would be just as effective. The sides aren’t bad just have to be mindful of what you eat. I take medicine for acid reflux and it does not help.

It’s the constipation you should be worrying about lol. Yes. I’ve tried it. What I found is that if I take one “higher” dose once a week I’m not hungry at all but that’s because I’m constipated to all hell. If I take same dose split in two for the week I don’t get as constipated but also don’t get as good appetite suppression. It’s almost like you need to take a weekly dose and then a bunch of laxatives right before next dose to get the most out of it. The constipation got old. Let us know how it dose for you.

 

[Kluso]

Thought about trying it for me and my wife to drop a few lbs before going to the keys but heart burn sounds like a no deal for me

Didn’t have that issue personally. Wife didn’t either.

 

[Kluso]

I've consider doing the every 2 to 3 nights and see what changes I'm going to try and tough it out until my next blood work in 3 months to see if there's any change one way or the other. At that point I'll probably go ahead if I have to start making some adjustments to my acid reflux regimen so to speak. I found that Ginger root helps a lot. If it gets really bad I do some baking soda but I have to be careful of that because I have high blood pressure and extra sodium is definitely not good for me.


I have dealt with heartburn my whole life honestly I remember even as a teenager having to eat rolaids but I also grew up in a very traumatic environment which I'm sure probably did not help any. Just sucks to have to be careful what I eat some things are way worse acidic foods make it worse spicy foods make it worse but I can have oatmeal and get terrible heartburn it's ridiculous.


I'm going through two more blood donations so in about 120 days I'm going to retest my hematocrit was way up I hadn't given blood in about a year and I'm making some changes my cholesterol was off a bit but that was due to some sloppy eating. That's all back on track and has been since my blood work. I like to see those numbers look a lot better.

I definitely appreciate the feedback. I think we're all going through the same thing as we age things change and we need as much information as we can get to make better choices

Just be careful what you eat because Dusty Hanshaw tore his esophagus eating a steak because he let his acid reflux go and it thinned his esophagus wall lining. Maybe start using astragalus to counter the kidney sides from the medicine. Vitamin shop brand is the go to that’s recommended by Dante. 6000mg Ed. It’s a lot of pills but works.

 

[Ms.Wetback]

I’ve tried that. I just think me & Sema just don’t get along.

Could try Tirz or Reta

 

[Wallyd]

Could try Tirz or Reta

Tirzepatide seems to be much better than senaglutide.

 

[MR. BMJ]

Semaglutide vs Tirzepatide for Weight Loss in Adults With Overweight or Obesity

This cohort study compares treatment-associated weight loss and rates of gastrointestinal adverse events among adults with overweight or obesity receiving tirzepatide or semaglutide labeled for type 2 diabetes in a clinical setting.

jamanetwork.com

FULL STUDY IN LINK

July 8, 2024

Semaglutide vs Tirzepatide for Weight Loss in Adults With Overweight or Obesity​

Patricia J. Rodriguez, PhD1; Brianna M. Goodwin Cartwright, MS1; Samuel Gratzl, PhD1; et alRajdeep Brar, MD1; Charlotte Baker, DrPH1; Ty J. Gluckman, MD2; Nicholas L. Stucky, MD1

Author Affiliations Article Information

JAMA Intern Med. Published online July 8, 2024. doi:10.1001/jamainternmed.2024.2525

Key Points
Question How does weight loss differ between patients receiving tirzepatide compared with semaglutide among a clinical population of adults with overweight or obesity?

Findings In this cohort study of 18 386 propensity-score matched patients initiating tirzepatide or semaglutide labeled for type 2 diabetes, discontinuation was common; most achieved weight loss of 5% or greater within 1 year of treatment.

Meaning Although most adults with overweight or obesity experienced 5% or greater weight loss with treatment, the benefit was greater with tirzepatide.

Abstract
Importance Although tirzepatide and semaglutide were shown to reduce weight in randomized clinical trials, data from head-to-head comparisons in populations with overweight or obesity are not yet available.

Objective To compare on-treatment weight loss and rates of gastrointestinal adverse events (AEs) among adults with overweight or obesity receiving tirzepatide or semaglutide labeled for type 2 diabetes (T2D) in a clinical setting.

Design, Setting, and Participants In this cohort study, adults with overweight or obesity receiving semaglutide or tirzepatide between May 2022 and September 2023 were identified using electronic health record (EHR) data linked to dispensing information from a collective of US health care systems. On-treatment weight outcomes through November 3, 2023, were assessed. Adults with overweight or obesity and regular care in the year before initiation, no prior glucagon-like peptide 1 receptor agonist receptor agonist use, a prescription within 60 days prior to initiation, and an available baseline weight were identified. The analysis was completed on April 3, 2024.

Exposures Tirzepatide or semaglutide in formulations labeled for T2D, on or off label.

Main Outcomes and Measures On-treatment weight change in a propensity score–matched population, assessed as hazard of achieving 5% or greater, 10% or greater, and 15% or greater weight loss, and percentage change in weight at 3, 6, and 12 months. Hazards of gastrointestinal AEs were compared.

Results Among 41 222 adults meeting the study criteria (semaglutide, 32 029; tirzepatide, 9193), 18 386 remained after propensity score matching. The mean (SD) age was 52.0 (12.9) years, 12 970 were female (70.5%), 14 182 were white (77.1%), 2171 Black (11.8%), 354 Asian (1.9%), 1679 were of other or unknown race, and 9563 (52.0%) had T2D. The mean (SD) baseline weight was 110 (25.8) kg. Follow-up was ended by discontinuation for 5140 patients (55.9%) receiving tirzepatide and 4823 (52.5%) receiving semaglutide. Patients receiving tirzepatide were significantly more likely to achieve weight loss (≥5%; hazard ratio

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, 1.76, 95% CI, 1.68, 1.84; ≥10%; HR, 2.54; 95% CI, 2.37, 2.73; and ≥15%; HR, 3.24; 95% CI, 2.91, 3.61). On-treatment changes in weight were larger for patients receiving tirzepatide at 3 months (difference, −2.4%; 95% CI −2.5% to −2.2%), 6 months (difference, −4.3%; 95% CI, −4.7% to −4.0%), and 12 months (difference, −6.9%; 95% CI, −7.9% to −5.8%). Rates of gastrointestinal AEs were similar between groups.

Conclusions and Relevance In this population of adults with overweight or obesity, use of tirzepatide was associated with significantly greater weight loss than semaglutide. Future study is needed to understand differences in other important outcomes.

 

[MR. BMJ]

Randomized Controlled Trial

Clin Nutr 2024 Aug;43(8):1907-1913.
doi: 10.1016/j.clnu.2024.06.034. Epub 2024 Jul 2.

Metabolic effects of very-low calorie diet, Semaglutide, or combination of the two, in individuals with type 2 diabetes mellitus​

Oluwaseun Anyiam 1, Bethan Phillips 2, Katie Quinn 3, Daniel Wilkinson 2, Kenneth Smith 2, Philip Atherton 4, Iskandar Idris 5

• PMID: 38996661

Metabolic effects of very-low calorie diet, Semaglutide, or combination of the two, in individuals with type 2 diabetes mellitus - PubMed

VLCD elicited greater short-term losses of weight and fat mass than Semaglutide. Adding VLCD to Semaglutide stimulated further weight loss than Semaglutide alone. The combination did not yield any additive effects on weight and body composition above VLCD alone, but did provoke greater...

pubmed.ncbi.nlm.nih.gov

Abstract​

Background & aims: Very-low calorie diets (VLCD) and the glucagon-like peptide-1 receptor agonist (GLP1RA) Semaglutide induce significant weight loss and improve glycaemic control in individuals with type 2 diabetes (T2D). This pilot study was conducted to explore the comparative short-term effects of these interventions individually, and in combination, on weight, body composition and metabolic outcomes.

Methods: Thirty individuals with T2D (age 18-75 years, BMI 27-50 kg m-2) were randomly assigned to receive Semaglutide (SEM), 800 kilocalorie/day VLCD (VLCD), or both in combination (COMB) for 12 weeks. Measurement of weight and glycated haemoglobin (HbA1c), dual energy X-ray absorptiometry, and intravenous glucose tolerance tests (IVGTT) were performed at baseline and post-intervention. Diet diaries were utilised to assess compliance. Insulin first phase response during IVGTT provided a marker of pancreatic beta-cell function, and insulin sensitivity was estimated using HOMA-IR.

Results: Significantly greater reductions in body weight and fat mass were observed in VLCD and COMB, than SEM (p < 0.01 v both). VLCD and COMB resulted in a 5.4 and 7 percentage-point greater weight loss than SEM, respectively. HbA1c and fasting glucose reduced significantly in all groups, however fasting insulin and HOMA-IR improved in VLCD and COMB only. Insulin first phase response during IVGTT increased in SEM and COMB, and this increase was significantly greater in COMB than VLCD (p < 0.01).

Conclusion: VLCD elicited greater short-term losses of weight and fat mass than Semaglutide. Adding VLCD to Semaglutide stimulated further weight loss than Semaglutide alone. The combination did not yield any additive effects on weight and body composition above VLCD alone, but did provoke greater improvements in pancreatic beta-cell function. Thus, combination of Semaglutide and VLCD warrants further exploration as a novel approach to T2D management.

 

[MR. BMJ]

Why you should not skip tailored exercise interventions when using incretin mimetics for weight loss

www.ncbi.nlm.nih.gov

Modern incretin mimetics are a hot topic in the treatment of adults with obesity or overweight (1). Weekly subcutaneous injections of glucagon-like peptide-1 (GLP-1) receptor agonists (RAs) or dual GLP-1/glucose-dependent insulinotropic polypeptide (GIP) RAs have been shown to elicit weight reductions of up to 15–20% in adults with obesity or overweight (2, 3) – levels of weight loss previously reported only after bariatric surgery.

The effects of GLP-1 RAs are manifold: they increase postprandial insulin secretion from pancreatic β-cells, suppress glucagon secretion from α-cells, slow gastric emptying, and reduce appetite. The suppression of appetite under GLP-1 RA treatment is presumably induced by actions on peripheral vagal nerve endings in the gut mucosa that project into the central nervous system, engaging satiation signals.

Whether and how incretin mimetics can access central brain targets relevant for appetite suppression is a subject of current debate (4). While the precise mechanisms behind the hypophagic effects of GLP-1 RAs are still not fully understood, GLP-1 RAs like liraglutide or semaglutide, as well as tirzepatide, a GLP-1/GIP RA, have been authorized for weight loss as an adjunct therapy to lifestyle interventions in adults with obesity (body mass index (BMI) of ≥ 30 mg/m²) or adults with overweight (BMI ≥ 27 mg/m² but ≤ 30 mg/m²) who have at least one weight-related health problem.

However, in practice, diet and exercise may risk being overshadowed by what has been described as a “miracle drug” in public media. Here, we present some reasons why regular exercise is crucial during and after incretin-based pharmacotherapy for people who want to lose weight.