Today, we’re diving into GLP‑1 therapies, including dual GIP/GLP‑1 agonists and the emerging triple agonists, and talking about how these peptides are typically dosed, what people are experimenting with, and what the research — or real-world experience — tells us so far.
Most GLP‑1 receptor agonists, as well as dual and triple agonists, are designed for weekly dosing. This is based on their half life.
Let me try to explain.
When we say a peptide like a GLP‑1 receptor agonist has a 7‑day half-life, that means it takes roughly 7 days for the concentration of the peptide in the blood to decrease by half after a dose.
In the context of pharmacokinetics — which is the study of how the body absorbs, distributes, metabolizes, and eliminates a peptide — this has several important implications.
- Steady Blood Levels: Because the peptide hangs around in the body for a long time, you don’t need daily injections to maintain its effect. Weekly dosing is enough to keep the peptide at a relatively stable level in your blood.
- Accumulation and Maintenance: After the first dose, it takes a few weeks for the peptide to reach a steady-state concentration, meaning the amount coming in with each dose balances the amount leaving the body. For a peptide with a 7-day half-life, this usually happens after about 4–5 weeks of weekly injections.
- Consistent Effect: The long half-life helps smooth out peaks and troughs in peptide concentration. This means appetite suppression, blood sugar effects, and weight-loss benefits are more consistent over the week, rather than spiking right after a dose and dropping off quickly.
- Flexibility in Dosing: The long half-life also explains why some people experiment with micro-dosing or every-other-week dosing — the peptide remains in the system, so the effect doesn’t disappear immediately if a dose is skipped or spaced out. However, the level may gradually drop, which can slightly reduce effectiveness over time.
In short: the 7-day half-life is why weekly injections work so well — it keeps the peptide in the bloodstream long enough to maintain steady effects, allows predictable weight loss and appetite suppression, and gives flexibility in dosing strategies.
Clinical trials have used weekly dosing as the standard, so that’s where we have the most safety and efficacy data. Tirzepatide, for example, is a dual GLP‑1/GIP agonist, and triple agonists like retatrutide combine GLP‑1, GIP, and glucagon receptor activity. These multi-receptor peptides are showing very promising results for weight loss and metabolic health, and weekly dosing remains the most common schedule in research.
That said, in real-world practice, some people are exploring micro-dosing or every-other-week dosing. Micro-dosing involves giving smaller-than-standard amounts, often to reduce side effects like nausea or gastrointestinal discomfort.
Every-other-week dosing can save money, reduce injection burden, or allow patients who don’t need the full standard dose to maintain their response.
Why does this matter? It comes down to flexibility and personalization. Standard weekly dosing works very well for most people, particularly during the initial weight-loss phase or when metabolic improvements like better blood sugar control are the goal. But once goal weight is achieved, spacing doses out or micro-dosing can be a way to maintain results while minimizing side effects, cost, or injection burden. The key is that these decisions should be individualized and done under clinical supervision, with regular monitoring of weight, appetite, metabolic markers, and overall tolerance.
Real-World Observations & What We Know So Far
In recent months, researchers have begun to study what happens when people dial back from standard weekly dosing — either by spacing out injections (every 2‑4 weeks) or by using lower-than-standard “micro‑doses.” One of the first published looks at this is a 2025 case‑series + modeling study, where two real‑world patients used their agents less often than recommended, coupled with a pharmacokinetic/pharmacodynamic simulation modeling “virtual patients.” The results were encouraging: both actual and virtual patients maintained substantial amounts of their original weight loss even with reduced dosing frequency.
Modeling studies and small case reports suggest that these approaches may preserve a substantial portion of the benefits — one study even predicted around 75% of weight loss could be maintained with every-other-week dosing. However, it’s important to emphasize that these approaches are off-label and haven’t yet been validated in large, long-term trials.
These results suggests that — at least for maintenance (after the initial weight-loss phase) — less frequent dosing might be a viable compromise: lower cost, fewer injections, and still significant benefit. This could be especially appealing for people who have already lost weight and want to maintain, rather than continue aggressive weight loss.
What We DON’T Know — And What We Should Be Cautious About
But before getting too excited, it’s important to keep a few key limitations in mind.
Because of the way the peptides are metabolized, extending the interval can lead to fluctuating levels — meaning periods where plasma concentration might drop too low to maintain the full appetite suppression or metabolic effect. This raises concerns about possible weight regain, loss of glycemic/metabolic benefits, or return of appetite (“food noise”) — especially if lifestyle support (diet, protein intake, hydration, activity) is not sustained.
There’s also the issue of patient selection: this approach may work better in “responders” — people who responded well to weekly dosing, lost weight, and adopted durable lifestyle changes. It may not work as well for someone who was a “non‑responder” or had difficulty with appetite regulation or metabolic improvements.
Finally, because this is off-label and not widely studied, there are a few practical considerations. Depending on the prescriber, they may not be able to get insurance to cover the medication if they’re willing to write a prescription for micro-dosing or alternative schedules. Also, the prefilled pens for Wegovy and Zepbound come in fixed doses, so if someone wants a truly tailored micro-dose, it would need to come from a compounding pharmacy, which adds another layer of complexity and cost.
What This Means for Patients (Especially in a Clinical Setting)
If I were advising a patient or designing a treatment plan, here’s how I’d approach it based on what we know so far. I’d start with standard weekly dosing during the initial weight-loss phase or for metabolic optimization, especially if the goal is significant fat loss, appetite suppression, improved insulin sensitivity, or other metabolic benefits. This is still the regimen with the strongest evidence behind it.
Once the patient reaches their goal weight — and assuming they’re stable, have implemented lifestyle changes, and are tolerating the medication well — we might consider transitioning to extended-interval dosing, like every two weeks, as a maintenance strategy. This can help make therapy more sustainable over the long term, reduce costs, and improve quality of life.
Throughout the process, lifestyle support remains key. A balanced diet with enough protein, staying hydrated, regular physical activity, quality sleep, and nutrient-rich foods all help maintain results. The medication is a tool, but long-term success often depends on these habits.
It’s also important to monitor progress carefully. Track weight, appetite, metabolic markers, side effects, and overall wellness. If weight starts creeping back up or appetite returns, adjustments to the dose or dosing interval may be needed.
Finally, this should always involve shared decision-making. Because the data on extended-interval or micro-dosing is limited, any approach should be tailored to the individual — considering their health history, response to therapy, financial situation, and personal preferences.
Thanks for listening to The Peptide Podcast
Until next time, be well, and have a happy, healthy week.
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