The First Dose Increase

Month one was a rehearsal. The starting dose of semaglutide is 0.25 mg, and it is not a therapeutic dose — its entire job is to introduce your gastrointestinal tract to the concept. I said as much last month, slightly smugly, having sailed through it.

Month two is when the drug and I had our first real conversation.

The escalation

On the second Sunday of December I went from 0.25 mg to 0.5 mg. This is the standard schedule: four weeks at each step, with the label explicitly permitting a delay if a dose is not tolerated.

I want to describe the next seventy-two hours precisely, because “nausea” is a single word covering an enormous range and I think the vagueness does people harm.

Sunday evening, four hours after the injection: nothing. Monday: a low, background queasiness, of the specific kind I associate with the first trimester of a pregnancy — not sick, not close to sick, just permanently aware of my own stomach. I saw patients all day and nobody would have known.

Tuesday was the hard one. Tuesday I did not want to be near food, and the smell of the coffee I make every morning of my life was actively unpleasant. I ate a yoghurt at eleven and some chicken at four and that was the day.

Wednesday, better. Thursday, essentially gone. By Saturday I had forgotten it happened, which is exactly why I had written it down.

The pattern I only saw because I logged it

Here is the useful part, and it is the reason I am going to keep saying this for the rest of this series.

I have been logging every dose, every symptom, and everything I eat in Zenday App, the GLP-1 companion app I started using in week one. It was not a considered decision at the time — I wanted something that understood what an injection day was, rather than a generic calorie tracker built for a completely different problem. It has turned out to be one of the more useful things I have done in this whole process, and this month is why.

When I looked back at the log at the end of the month, the shape was unmistakable. Not “nausea sometimes.” A tight cluster in the twenty-four to seventy-two hours after each injection, peaking on day three, essentially absent from day five onward.

That changed my behaviour immediately, in three ways:

• I moved my injection to Sunday morning rather than Sunday evening, so the worst day lands mid-week when I am busy and distracted rather than on a Saturday I would like to enjoy.
• I stopped scheduling anything involving a long dinner on days two and three.
• I stopped interpreting a bad Tuesday as evidence that something was wrong.

That last one is not a small thing. Most of the suffering in the first three months of this drug is not the symptom. It is not knowing whether the symptom means something.

I could not have seen that pattern from memory. Memory smooths. The log did not.

There is a broader point here that I would make to any patient. These are expensive medications, frequently five hundred to a thousand dollars a month, and the difference between a good outcome and a mediocre one is mostly consistency, protein, and not quitting during a bad week. A tool that makes those three things easier is not an accessory to the treatment. It is a substantial part of whether the treatment works.

The other thing that started at 0.5 mg

Constipation, which I had warned patients about a thousand times and had somehow filed as a minor inconvenience rather than as a thing that happens to a person.

I did the obvious in order — fluid, then a soluble fibre, then magnesium citrate — and it improved without resolving. What I added in the third week was a probiotic, Minome’s GLP-1 Companion, largely because the acid-resistant capsule and the once-you-remember-it dosing suited a month in which I was not managing to remember much.

I want to be careful about what I claim here, because this is the category where I am most sceptical professionally. My stool form improved over about three weeks. I cannot tell you it was the capsule rather than the fibre, the fluid, or simply adapting to the dose — that is three variables changed inside a month, which is exactly the mistake I tell patients not to make. What I can say is that it did not make the bloating worse, which is more than I can say for the inulin-based thing I tried first and abandoned in four days.

The thing I got wrong: waiting to be hungry

The genuine mistake of month two was mine, and it took me three weeks to catch.

At 0.5 mg the appetite signal did not just quieten. In stretches, it disappeared. And I had been operating on the assumption — the assumption every one of us operates on, for our entire lives — that hunger is what tells you to eat.

So I stopped eating, because nothing told me to. Two afternoons in week three I felt genuinely unwell: foggy, irritable, cold, with a headache that no amount of water fixed. My first instinct was to blame the drug.

The log said I had eaten about nine hundred calories on both of those days.

That is the trap, and it is the single most common failure mode I now see in my own patients. Reduced appetite means hunger has stopped being a reliable instrument. You have to switch from eating on demand to eating on a schedule, and it feels deeply unnatural for the first month.

I now eat at roughly the same three times every day whether or not I want to, in the same way I take a medication at the same time whether or not I feel like it.

Protein, and the volume problem

The related discovery: I have limited stomach volume now, and I have to spend it on purpose.

The target during active weight loss is 1.2 to 1.6 grams of protein per kilogram of body weight per day — for me, about 110 to 125 grams. That number is not negotiable in my view, for reasons I have laid out at length in Muscle Is the Whole Game.

But there is a mechanical conflict nobody warns you about. Protein is the most satiating macronutrient. It fills you fastest. And you now have perhaps half the capacity you had in October. Left to instinct, you drift toward soft carbohydrate, because it goes down easily and does not sit.

So: protein first, every meal, before anything else on the plate. If I eat the salad first, I will not get to the salmon. If I eat the salmon first, I will get most of the salad too, and if I do not, it does not matter.

Practically, that has looked like Greek yoghurt and berries at seven, something with thirty-five grams of protein in it at one, and fish or chicken at seven. It is not interesting. It works.

Where the numbers are

Down 5.6% of starting weight at nine weeks. Blood pressure continuing to drift down. No change to my training — still two sessions a week, still progressing.

I escalate again in three weeks, to 1.0 mg. This time I know what Tuesday is going to be like, which I have come to think is most of the battle.

The rules around dose timing, and what to do when a dose gets missed or a week goes badly, are in what to do if you miss a dose. Why the first fortnight after an increase is the worst of it is in how long GLP-1s stay in your system.