Lower starting doses

[Calm Logic]

So should people start on 1.0 mg of tirz? I don't think so. There's always exceptions, but almost no one does that. The 2.5 mg dose is considered the lowest, initiation dose for tirz, with a current maximum of 15 mg that is six times that.

I think part of the confusion is because people lose so much weight initially, even dieting on their own. But the bloodwork improvements and other therapeutic effects are still dose-dependent.

Though appetite suppression is highly variable, and I had good suppression even at 2.5 mg of tirz starting out, the therapeutic dose is 5 mg and up for tirz.

In other words, I don't think anyone gets the full benefits of reta or tirz at 0.5 mg or 1.0 mg or 2.5 mg, at least regarding glucose control and anti-inflammatory effects, which relate to off-label gains like less anxiety/depression or more cognitive health. Anxiety, depression, and most other conditions are now seen as partly due to inflammation.

 

[Calm Logic]

From Google Gemini, regarding tirz:

Based on the data, particularly for weight loss and hsCRP reduction, the increase in anti-inflammatory effect from 10 mg to 15 mg is present but less dramatic than the jump from the initiation 2.5 mg dose to the therapeutic 5 mg dose.

Tirzepatide Dose-Dependent Effects Summary
​

Tirzepatide Dose (mg)	Primary Purpose / Role	Average Weight Loss (Approx. % from Baseline)	HbA1c Reduction (Approx. % from Baseline)	Anti-Inflammatory Effects (Qualitative)	Common Side Effects (General)
2.5 mg	Initiation Dose	Small to Modest (e.g., 3-5% for short term)	Moderate (e.g., 1.5-1.8%)	Mild; primarily due to early metabolic shifts.	Nausea, diarrhea, constipation, vomiting
5.0 mg	Therapeutic Dose	Significant (e.g., 15-16% in SURMOUNT-1)	Substantial (e.g., 2.0-2.2%)	Moderate to Substantial; driven by significant weight loss & glycemic control.	Nausea, diarrhea, constipation, vomiting (often less severe than initial)
7.5 mg	Therapeutic Dose	High (e.g., 18% in SURMOUNT-1)	Very Substantial (e.g., 2.1-2.4%)	More substantial; continued improvement in metabolic health.	Similar, but often stable or improving for many
10.0 mg	Therapeutic Dose	Very High (e.g., 19.5% in SURMOUNT-1)	Very Substantial (e.g., 2.2-2.5%)	Very substantial; strong impact on systemic inflammation through metabolic benefits & direct effects.	Similar, often well-tolerated at this stage
12.5 mg	Therapeutic Dose	Extremely High (e.g., ~20% based on trends)	Extremely Substantial (e.g., 2.3-2.6%)	Approaching maximal anti-inflammatory effect.	Similar, but generally well-tolerated if patient has titrated up
15.0 mg	Therapeutic Dose	Highest (e.g., 20.9% in SURMOUNT-1)	Likely maximal anti-inflammatory effect; highest impact on inflammatory markers & metabolic health.	Similar; often the highest dose tolerated for sustained effect

Note: This table provides general observations from clinical trials. Individual responses may vary.
​

Speculative "Guess Percentages" for Incremental Anti-Inflammatory Effect of Tirzepatide Doses

Dose Progression	Estimated Incremental Increase in Anti-Inflammatory Effect (Guess %)	Rationale (Based on General Trends)
2.5 mg to 5.0 mg	50% - 100%+	This is the largest conceptual leap. 2.5 mg is an initiation dose; 5.0 mg is the first dose intended for significant therapeutic effect (weight loss, glycemic control), leading to a proportionally much greater impact on inflammation.
5.0 mg to 7.5 mg	5% - 15%	A consistent, noticeable step up. Continues to improve weight loss and metabolic control incrementally.
7.5 mg to 10.0 mg	8% - 18%	A solid step further into the main therapeutic range. Expected to provide a slightly more robust increase than the previous step as efficacy optimizes.
10.0 mg to 12.5 mg	5% - 12%	Continued improvement, but as the dose approaches the higher end, the incremental gains may start to slow slightly per mg.
12.5 mg to 15.0 mg	3% - 10%	The final step to the highest approved dose. Benefits are still present but represent the final push towards maximal efficacy, where the dose-response curve is at its flattest.

Critical Disclaimers:

• These percentages are estimates and not backed by direct comparative studies isolating the anti-inflammatory effect between every adjacent dose.
• "Anti-inflammation" is a complex concept encompassing various markers and pathways; it's not a single, universally quantified metric.
• The 2.5 mg dose is primarily for initiation and tolerability, so the jump to 5.0 mg (the first therapeutic dose) often represents the most significant relative increase in efficacy.
• As doses increase, while effects continue to improve, the incremental benefit per milligram tends to diminish (i.e., the dose-response curve flattens).
• Individual patient responses can vary significantly.

 

[zpped]

So should people start on 1.0 mg of tirz? I don't think so.

I do. I've seen lots of people get good starting results on 1mg. Do most people do ok with 2.5? Sure, but a lot of people also end up with nasuae, constipation, or diarrhea at that dose.

What's the downside of spending a few weeks at 1mg?

 

[Calm Logic]

What's the downside of spending a few weeks at 1mg?

Lower efficacy, of course. And yes, it can be a trade-off with side effects.

Are these people monitoring their blood sugar continuously? How did glucose control at 1 mg (20 percent of the therapeutic dose) compare to higher doses later on?

And anybody with high triglycerides or a fatty liver should not be monkeying around by lowering the dosing schedule.

If one's labs are already good, that's one thing. But most people starting on GLPs are not in that category. And if one orders enough labwork like hs-CRP, there may be something abnormal that was undetected before.

 

[Calm Logic]

I have seen it all now, with placebo starting doses of 0.01 mg for sema (less than half a percent of the max dose of 2.4 mg) and 0.3 mg for tirz (2 percent of the max):

https://www.reddit.com/r/GLP1microdosing/

https://www.reddit.com/r/GLP1microdosing/comments/1jwygp0/whats_the_lowest_does_you_started_at

But they have zero side effects 🙃

 

[zpped]

Lower efficacy, of course. And yes, it can be a trade-off with side effects.

Are these people monitoring their blood sugar continuously? How did glucose control at 1 mg (20 percent of the therapeutic dose) compare to higher doses later on?

And anybody with high triglycerides or a fatty liver should not be monkeying around by lowering the dosing schedule.

If one's labs are already good, that's one thing. But most people starting on GLPs are not in that category. And if one orders enough labwork like hs-CRP, there may be something abnormal that was undetected before.

I'd say it's a little alarmist to say that an extra month of (absolute worst case) living with whatever condition someone has been in for many years is going to be that detrimental in the long term. I've coached 7 people in my personal life to start at 1mg of tirz and they all lost at least 2lb a week for the first month. A handful of them stayed under 2.5mg for 4 months while continuing to lose at that rate.

On the flip side, I know people that had a bad time on the pharma starting dose and quit after 2 weeks deciding that it wasn't for them. And many others who say they don't even want to try because they are afraid of the side effects.

 

[Calm Logic]

From what I see online, most microdosers are alarmist about side effects, especially since they can be mitigated with meds and/or diet modifications. Some have not seen their own doctor about GLPs at all, so they are already less likely to seek out medical support to manage dosing or sides. Granted, some of them are not even overweight and are optimizers.

What I don't see enough of: People using telehealth to manage GI symptoms. A person could even schedule weekly telehealth appointments with a board-certified internist. Or just use Amazon telehealth as needed. But the microdosers, to be consistent, may want to microdose GI meds too, haha.

OTOH, one can even argue that GI sides can help attenuate rewards with ultraprocessed and fatty foods: "Gastric malaise may contribute to the anti-obesity effects of GLP-1 agonists." A former head of the FDA, Dr. Kessler, says the same thing in his new book on GLPs. But meds for sides is the way to go if even crackers will trigger stomach upset.

What you and the microdosing community don't have is sufficient data. Not even a single printout from Labcorp, let alone and before-and-after labs or CGM data for below-starting doses. And even then, you would have to compare that to a standard treatment group.

And there is already delay in the dosing schedules, such as four weeks of tirz at 2.5 mg. A lot of people are already impatient with that and rightly so if they are doing fine.

But in the spirit of quasi-science, I propose daily liraglutide from India as a stepping stone 🙂 The short-half life makes it easy to stop before you start, if need be.

 

[Calm Logic]

Prescription Medications for Managing GI Side Effects from GLP-1 RAs

by Google Gemini

GLP-1 receptor agonists (GLP-1 RAs) are known to cause a range of gastrointestinal (GI) side effects, primarily due to their action of slowing gastric emptying and influencing gut hormones. While many individuals find these symptoms lessen over time or can be managed with lifestyle and dietary adjustments, some may require prescription medications for effective relief. It's crucial to remember that all medications mentioned below require a prescription and should only be used under the guidance of a healthcare professional. The specific choice of medication will always depend on the individual's symptoms, their severity, overall health, and potential interactions with other medications.

Managing Nausea & Vomiting

For nausea and vomiting, a common class of medications is antiemetics. Ondansetron (Zofran) is often a primary choice, valued for its effectiveness and relatively mild side effect profile, and can be taken as needed. Other antiemetics include prochlorperazine (Compazine) and metoclopramide (Reglan). Prochlorperazine is effective but may cause drowsiness. Metoclopramide is notable because it can also help to speed up gastric emptying, which might be beneficial if delayed emptying is contributing to the nausea; however, it carries a risk of tardive dyskinesia with long-term use. Additionally, promethazine (Phenergan) and the scopolamine patch (Transderm Scop), which are antihistamine/anticholinergic antiemetics, can be used for more severe or persistent nausea, but they may cause sedation and dry mouth.

Addressing Constipation

Constipation is another frequent GI side effect. Osmotic laxatives like lactulose and polyethylene glycol (PEG, e.g., MiraLAX) work by drawing water into the colon to soften stool, making it easier to pass. Stronger prescription formulations of PEG may be available. These are generally well-tolerated, though lactulose can sometimes cause bloating. Stimulant laxatives, such as prescription-strength bisacodyl (Dulcolax) or senna (Senokot), act by stimulating intestinal muscles to promote bowel movements. These should be used cautiously and typically not for long-term daily use due to the risk of dependence and electrolyte imbalances. Newer prescription options include chloride channel activators like lubiprostone (Amitiza), which increase fluid secretion in the intestine, and guanylate cyclase-C (GC-C) agonists such as linaclotide (Linzess) and plecanatide (Trulance), which increase both fluid secretion and transit time. These are effective for chronic constipation and can also be helpful for constipation-predominant irritable bowel syndrome (IBS-C), but diarrhea is a potential side effect. Finally, prucalopride (Motegrity), a serotonin 5-HT4 receptor agonist, specifically targets and stimulates colonic peristalsis to alleviate chronic idiopathic constipation.

Relieving Diarrhea

While constipation is common, some individuals may experience diarrhea. Anti-motility agents like prescription-strength loperamide (Imodium) are frequently used. Loperamide works by slowing down intestinal movement, which allows more water to be absorbed from the stool, making it firmer. It is generally safe for short-term use. In cases where diarrhea might be linked to bile acid malabsorption (though less directly caused by GLP-1 RAs), bile acid sequestrants such as cholestyramine (Questran), colestipol (Colestid), and colesevelam (Welchol) can be considered, as they bind bile acids in the gut. An antisecretory agent like octreotide (Sandostatin) is rarely used for typical GLP-1 RA side effects; it's a highly potent medication reserved for very severe, refractory diarrhea, often in specific medical conditions like neuroendocrine tumors, and is usually managed by specialists.

Alleviating Abdominal Pain & Cramping

Abdominal pain and cramping can be quite uncomfortable. Antispasmodics like dicyclomine (Bentyl) and hyoscyamine (Levsin) are prescribed to reduce muscle spasms in the gut, which can help ease cramping and associated pain. These medications can cause anticholinergic side effects such as dry mouth and constipation. For chronic or more persistent abdominal pain, particularly if it resembles neuropathic or visceral hypersensitivity pain (as seen in conditions like IBS), low doses of tricyclic antidepressants (TCAs) such as amitriptyline (Elavil) or nortriptyline (Pamelor) may be prescribed. These are used for their neuromodulatory effects on the gut rather than their antidepressant properties, and the doses are much lower. Similarly, duloxetine (Cymbalta), an SNRI, might be considered in low doses, especially if other pain conditions or overlapping GI issues are present, though it's less common for primary GLP-1-induced pain.

Reducing Bloating & Gas

Bloating and gas, often associated with delayed gastric emptying, can sometimes be helped by prokinetics like metoclopramide (Reglan) (as mentioned under nausea). This medication can help to speed up the movement of food through the digestive tract. However, its use is balanced against the risk of tardive dyskinesia. While not a prescription medication, gut-directed hypnotherapy and other behavioral therapies are increasingly recognized and often recommended by GI specialists as an adjunctive approach for persistent functional GI symptoms, including bloating and discomfort.

Crucial Considerations: Before any prescription medication is considered, a healthcare provider will thoroughly evaluate the symptoms to rule out other, potentially more serious, underlying conditions. Often, the initial strategy for managing persistent side effects is to adjust the GLP-1 RA dose or slow down the titration schedule. Emphasizing dietary and lifestyle modifications, such as eating smaller, more frequent meals, avoiding high-fat or spicy foods, and ensuring adequate hydration, remains a vital first step. Treatment is always individualized, and all prescription medications carry their own potential side effects and drug interactions that must be carefully considered by a healthcare professional. Always consult with your doctor before making any changes to your medication regimen.

 

[Calm Logic]

Probiotics and Prebiotics for GLP-1 Side Effects:

By Google Gemini

GLP-1 receptor agonists (GLP-1 RAs) like Ozempic, Wegovy, and Mounjaro are highly effective for managing diabetes and aiding in weight loss, but they commonly cause gastrointestinal (GI) side effects such as nausea, vomiting, diarrhea, and constipation. Supporting a healthy gut microbiome with probiotics and prebiotics can sometimes help to alleviate these issues.

In certain severe cases of GI distress, a healthcare provider might consider recommending high-potency, medical-grade probiotics...such as Visbiome (formerly known as VSL#3 DS). While not specifically indicated for GLP-1 side effects, its robust formulation might be considered by a doctor. [cheap alternative]

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When seeking over-the-counter probiotics and prebiotics for GLP-1 induced GI side effects, a multi-faceted approach often works best, including dietary adjustments and good hydration. The most effective probiotic strain can vary depending on the individual and their specific symptoms.

For nausea, some products combine probiotics with ginger extract, which is known for its anti-nausea properties. Examples include Youtheory GLP-1 Support 2x Action Probiotic, which contains a specific probiotic strain and ginger, or general probiotics like Lactobacillus acidophilus and Bifidobacterium lactis that aid in overall digestive comfort.

For constipation, look for probiotic strains like Bifidobacterium lactis (B. lactis), Lactobacillus rhamnosus, and Lactobacillus plantarum, which are known to support regularity. Some high-quality synbiotic products, like Seed Daily Synbiotic DS-01, or specialized ones like Pendulum Akkermansia or Metabolic Daily, contain a blend of strains and prebiotics to support overall gut health and promote regularity. Additionally, prebiotics such as Fructooligosaccharides (FOS) and Inulin, or fibers like psyllium husk, can feed beneficial gut bacteria and help soften stool.

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For diarrhea, specific probiotic strains are more effective. Saccharomyces boulardii, a well-researched yeast-based probiotic, is often recommended for various types of diarrhea and is found in products like Florastor. Other beneficial strains include Lactobacillus rhamnosus GG (LGG), commonly found in Culturelle, as well as Bifidobacterium lactis and Lactobacillus casei.

When choosing any probiotic or prebiotic, consider the CFU count (billions are usually better), the diversity of strains, and the reputation of the brand. Some probiotics require refrigeration, so always check the label. It's important to remember that it can take time to see the full effects, and individual responses vary, so you might need to try different options. Always consult with your healthcare provider or a registered dietitian before starting any new supplements, especially if you're taking prescription medications like GLP-1 agonists. They can ensure the supplements are appropriate for your health needs and won't interact with your current medications.

 

[zpped]

Posting a wall of AI output is not conducive to a conversation. I'm well aware of ways to mitigate the side effects through diet and other medications. That doesn't change my philosophy on the best way to mitigate side effects is a lower dose.

I'm not sure what you think my stance is because you seem to be implying I'm saying no one should ever take a bigger dose and that's definitely not what I'm advocating. I've also said MOST people will handle 2.5mg as a starting dose fine. But impatience is almost always what gets people into trouble too.

I'm moving this to its own thread since we've gone way topic of an intro post here.

 

[Calm Logic]

Smoothies and protein shakes become excellent tools for managing these side effects. Since liquids are easier to digest and leave the stomach faster than solids, they offer a gentler way to:

Reduce Nausea and Discomfort: Less time in the stomach means less discomfort.

Ensure Protein Intake: They provide an easily digestible, concentrated source of protein, crucial for fullness and muscle maintenance when appetite is low.

Prevent Dehydration/Malnutrition: When solid food is difficult, smoothies help maintain fluid and nutrient intake.

Offer Controlled Portions: Their satisfying nature makes smaller, nutrient-dense portions feel adequate.

GLP-1 Friendly Smoothie Template:

A good GLP-1 smoothie is high in protein, moderate in healthy fats, and lower in added sugars, aiming for easy digestion and satiety.

* Protein (1 scoop / 20-30g): Whey, casein, soy, or pea protein powder.

* Liquid Base (1/2-1 cup): Unsweetened almond/soy/oat milk, water, or coconut water.

* Fruit (1/2 cup, frozen): Berries (lower sugar), 1/2 banana, or 1/2 green apple.

* Healthy Fats (1-2 tbsp, optional): Chia/flax seeds, 1/4 avocado, or 1 tbsp nut butter.

* Veggies (1/4-1/2 cup, optional): Spinach, cooked zucchini, or cauliflower rice.

* Flavor Boosters (optional): Cocoa, cinnamon, vanilla extract, a pinch of stevia.

Berry Protein Power Smoothie:

This recipe balances protein, healthy fats, and controlled carbs for easy digestion.

Ingredients:

* 1 scoop (approx. 25g) unflavored or vanilla whey or plant-based protein powder

* 1 cup unsweetened almond milk (or water)

* 1/2 cup frozen mixed berries

* 1 tablespoon chia seeds
* Handful of fresh spinach (1/4 - 1/2 cup)

* 1/2 teaspoon vanilla extract (optional)

* Ice (optional)

Instructions:

* Add liquid to blender first, then protein powder, berries, chia seeds, spinach, and vanilla.

* Blend until completely smooth. Adjust liquid/ice for desired consistency.

* Pour and enjoy slowly.

Tips for Success:

* Sip Slowly: Don't drink too fast.

* Listen to Your Body: Adjust portions based on tolerance.

* Stay Hydrated: Drink plenty of water in addition to smoothies.

 

[Lilycatsmom]

I do. I've seen lots of people get good starting results on 1mg. Do most people do ok with 2.5? Sure, but a lot of people also end up with nasuae, constipation, or diarrhea at that dose.

What's the downside of spending a few weeks at 1mg?

Exactly. I had very bad nausea on the lowest doses of sema and Tirz so I advised my son to start at 1 mg of Tirz and we gradually increased him over eight weeks and is now on 5 mg. He has experienced zero negative side effects as opposed to my severe nausea at every increase at so-called suggested increments. Since there’s no emergency to get at a therapeutic dose, which can vary from person to person, this was the best choice for us.

 

[Calm Logic]

Well, that's interesting. Because most people who are wary enough to start at 1 mg are not going to get to 5 mg in eight weeks. Or so it seems when there are a number of Reddit people married to 2.5 mg of tirz for 20+ weeks.