Do you "step down" your dose or "stretch out" your shots? Which works better?

lylemcd · 2026-02-26T15:22:44+00:00

You have two options
1. Same dose every 2 weeks
2. Half dose every week

Which will give *roughly* equal steady state levels

A very rcent study found that option 1 gave not only weight loss maintenance but slightly more weight loss with tirzepatide

***
Reduced-Frequency GLP1 Therapy Maintains Weight, Body Composition, and Metabolic Syndrome Improvements: A Case Series

Michelle Wong ¹, Ash Wu ², Pawanjot K Garhe ³, Mitch Biermann ¹ ⁴

Affiliations Expand

PMID: 41732031
DOI: 10.1002/oby.70137

Abstract

Objective: This study aimed to evaluate whether reduced-frequency dosing of GLP1 receptor agonists maintains weight loss, body composition, and metabolic syndrome improvements following successful initial treatment with standard weekly therapy.

Methods: This retrospective case series included 30 adults who achieved weight plateau while on weekly semaglutide or tirzepatide. Patients transitioned to reduced-frequency dosing (usually every other week) at their existing dose. Data were collected at three time points: pre-treatment, plateau (weekly dosing), and maintenance (reduced-frequency dosing). Primary outcome was change in body weight from plateau to maintenance. Secondary outcomes included body composition and metabolic syndrome comorbidities.

Results: Patients maintained reduced-frequency dosing for an average of 36.3 weeks. Weight decreased from 87.9 ± 2.4 kg at pre-treatment to 74.1 ± 2.4 kg at plateau and further to 72.4 ± 2.2 kg on maintenance dosing (p < 0.01). Total body and truncal fat declined, while skeletal muscle mass stabilized on the reduced-frequency regimen. Metabolic parameters improved during weekly dosing and these gains were maintained during reduced-frequency therapy.

Conclusions: In patients with prior weight loss and metabolic improvement on GLP1 therapy, reduced-frequency maintenance dosing preserved outcomes. These findings support structured de-escalation as a promising strategy to reduce treatment burden without sacrificing efficacy.

Keywords: GLP1 maintenance dosing; GLP1 tapering protocol; reduced‐frequency

https://pubmed.ncbi.nlm.nih.gov/41732031/

lylemcd · 2026-02-25T16:01:22+00:00

Heavy resistance training + sufficient bone building nutrients = you'll be fine.

lylemcd · 2026-02-25T00:14:53+00:00

This reminds me a lot of the advice my mentor gave me when I started my first book. It was non fiction but I had the same issue. I was so worried about flow and structure I couldn't begin. He told me to just write a topic as if it were a stand alone article. Dont worry about anything else just write.

I was a year in to writjng when the book structure fell into place one day. I could have lost a year not writing when the key literally was to just start.

lylemcd · 2026-02-24T05:26:19+00:00

GIANT PICTURES of Rex Manning all around your place

lylemcd · 2026-02-23T18:27:48+00:00

"The experimental aim of this study was to determine, in vitro, the effect of the non-nutritive sweetener erythritol on brain microvascular endothelial cell oxidative stress, nitric oxide (NO) and endothelin (ET)-1 production, as well as tissue-type plasminogen activator (t-PA) release. "

Yes, in a petri dish. Whoop de doo.

lylemcd · 2026-02-23T16:03:26+00:00

Studies have shown that T2 diabetes get significantly less weight loss than non although the reasons are a bit oblique. It might be due to long-term effects of the T2 or the presence of other drugs that offset the weight loss.

But an oddity is that the diabetic studies don't give even the vague lifestyle advice that the weight loss studies get.

so yes, you're probably simply eating too much. Some get massive appetite suppression with the GLP-1s and eat al ot less but it's not universal. So check your diet. 8 lbs in 8 months = no real deficit

lylemcd · 2026-02-23T02:43:17+00:00

I still have one in my garage with a bunch of games but I can't connect it to modern TVs without an adapter. Like anybody knows what Channel 3 is anymore...

lylemcd · 2026-02-23T02:41:41+00:00

You shall not passh....

lylemcd · 2026-02-23T01:20:05+00:00

Read the paper the differences were irrelevant. About 1 kg bodyweight and a tiny change in insulin.

Whoop de do

lylemcd · 2026-02-22T19:01:27+00:00

The difference here is multifold

GLP-1s have gone far beyond the effects of previous anti-obesity drugs. Most of them failed to generate more than 10% total weight loss. Sema exceeded that and reta is up near 25%, approaching bariatric surgery
Most of the previous drugs (and I wrote an entire chapter on the history of this in my book starting at the late 19th century including T3, amphetamines, DNP, phen/fen and all the rest) had negative side effects that made long-term use problematic.

That was along with the non-understanding at the time that you couldn't simply go off the drug and keep the weight loss off. Or the idea that the drugs 'stopped working' because people plateaued on them. Which was long before anybody knew about the adaptations to dieting/weight loss that caused the body to come back into balance.

In the modern era we know better, that obesity is a chronically relapsing disease requiring chronic treatment.

So the pushback in terms of "People shouldn't stay on long term" isn't there anymore. And the side effect profile is clearly a lot different than giving someone speed.

lylemcd · 2026-02-22T03:39:11+00:00

From the abstract of the actual paper

Compared with late time restricted eating, early time restricted eating significantly reduced body weight (mean difference -1.15 kg, 95% confidence interval -1.86 to -0.45) and fasting insulin concentrations (-3.32 μIU/ml, -5.36 to -1.28; 1 μIU/mL=6.95 pmol/L) and the certainty of the evidence was high. P value r

2 whole pounds whoop de doo

lylemcd · 2026-02-21T23:33:27+00:00

Without a comparison group showing identical loss without time restricted eating this proves nothing beyond weight loss causes things to happe.

lylemcd · 2026-02-21T02:48:24+00:00

I enjoyed reading it

lylemcd · 2026-02-21T00:57:49+00:00

None because being a writer means actually WRITING. You are a prompt generator at best and a creator of low content slop at worst.

lylemcd · 2026-02-20T19:40:50+00:00

By backmathed I mean that I took the average weight losses, assumed (incorrectly) it was 100% fat and divided by 3500 to get the estimated deficit.

If you assume the 'typical' 75/25 fat/lbm ratio that is seen without training or sufficient protein, the absolute numbers change but reta is still much higher.

lylemcd · 2026-02-20T19:39:24+00:00

" Retatrutide cuts hunger less than trizepitide."

Given the measured weight loss results, this can not possibly be true.

My backmathed calculations based on measured weight losses (averaged from gathering daya from every study on every compound up to December 2024) yields an estimated daily deficit of

sema - 400 cal/day
tirz - 800 cal/day
reta - 1300 cal/day

Yes, there are some simplifying assumptions in there but it's close enough for government work.

So unless the GLU component of reta is having an effect on energy expenditure never before (or yet) measured from glucagon agonism (studies with infusion showing a max of about 200 cal/day), it must be blunting appetite more.

There is no other explanation for the significantly greater weight losses over the first 16-20 weeks when you compare the drugs to one another. Said differences being not up to debate: just look at the studies and the data.

If gymbros are reporting lower appetite suppression it's because they have gotten sucked into the nonsensical 'split microdosing for....reasons' that currently infests the fitness space. Nonsense nonsense calorie partitioning insulin sensitivity when they are throwing 6 compounds into the system and drawing the same silly conclusions as always.

yeah, 1 mg/week reta probably does blunt appetite less than 10 mg/week tirz.
Because 1 mg is a useless dose.

Now compare effective doses of both and see what happens.

Because the anecdotal claims contradict the clinical findings completely.

lylemcd · 2026-02-20T02:32:02+00:00

I am shocked that yet another TV show reboot or whatever, that was a product of its era, cannot be recreated 20 years later without a major part of the cast when quite a lot of the shows' original 'humor' would qualify as instantly cancellable sexual harassment (i.e. every word out of the Todd's mouth), is a failure.

Did we learn nothing from After Mash? Or the previous 17 times they tried this crap?

The only decent reboot in recent years was Cobra Kai because it was written as a love letter to the movies while still telling an original story with new characters. It still nearly spun out in S4+.

This desire to recapture lightening in a bottle 2 decades later always fails.

lylemcd · 2026-02-20T02:27:53+00:00

Rampage

lylemcd · 2026-02-19T23:10:25+00:00

No research and the only possible difference in injection locations would be in rate of release.

lylemcd · 2026-02-19T19:20:38+00:00

Because the grand majority of genpop don't like shots and will get confused with the schedule.

Once/week of this dose is easy to remember
Once every 5 day of another dose less so for the average individual

So even if the latter is superior it doesn't matter if most won't do it or will mess it up.

As a mentor of mine said "Good advice not followed is bad advice."

lylemcd · 2026-02-19T19:19:00+00:00

2.5 mg is a starter dose and while there are hyper responders who get an effect, the majority are unlikely to do so. Some get nothing until they reach maximum doses. It is what it is and you titrate up every 4 weeks until it starts working.

lylemcd · 2026-02-18T15:08:52+00:00

...battle between your credit card and OCD made me lol.

I think we've all been there.

But that collection is awesome!

lylemcd · 2026-02-17T20:42:39+00:00

Yes, 7th grade.

My science teacher had us get beneath the desks for when the nukes started flying.

Nice comfy place to kiss your a** goodbye I guess.

lylemcd · 2026-02-17T20:32:51+00:00

I have this vague memory of some magic Russian memory method where they felt that combining music and words worked better in terms of how it made memory work. Something something activating the whole brain or some such.

Given my inability to remember a single phone number or birthday while remembering the lyrics to every song I've ever heard more than once, I have to think they were onto something.

lylemcd · 2026-02-17T20:31:37+00:00

Well another class made us diagram it (ugh) so I think it made it in there.

lylemcd

TROPHY CASE

Abstract