Second pass at: Metformin co-administration and additive GI effects posts 61–90
This is a continuation of a long topic, addressed by post number rather than by page. Start at post 1.
The most defensible general position in this subcategory: identify the plausible mechanism, check whether it has been studied, and where it has not, say that rather than filling the gap.
Scoping that to what I have actually seen rather than what I have read.
The arithmetic in post #62 is right; the assumption feeding it is the part to check.
Having read the whole Metformin co-administration thread before replying: the question in the first post has not actually been answered yet, and three of us have answered a nearby one instead.
Answering the question post #62 raises rather than the one it answers.
An honest declaration on Metformin co-administration: I have a prior here and it is strong enough that you should weight what I say downward. Stating it rather than hiding it.
A pharmacist can answer most questions in this subcategory in a few minutes with access to a proper interaction database, and that access is the thing a forum does not have.
Metformin co-administration is worth one more sentence than it usually gets, and the sentence is the one about how the number was arrived at.
Collapsed as off-topic by two members at trust level 3 or above
Where a published interaction study exists it usually reports an area-under-curve ratio, and that number is far more informative than a yes-or-no answer.
It is worth checking rather than assuming, which costs nothing.
Post #67 is right about the mechanism and I think understates the practical bit.
Metformin co-administration would be much easier to settle if anyone reported the denominator. Almost nobody reports the denominator.
Same experience here, different supplier, so it is at least not unique to one of them.
Collapsed as off-topic by two members at trust level 3 or above
The most defensible general position in this subcategory: identify the plausible mechanism, check whether it has been studied, and where it has not, say that rather than filling the gap.
Written quickly, so the reasoning may be tighter than the wording.
Worth separating two things that post #69 runs together.
A definition problem is doing most of the work in this Metformin co-administration discussion. Once the term is pinned down I suspect the disagreement mostly goes away and what is left is small.
I would be cautious about generalising from the Metformin co-administration example above. It is a good example. It is one example.
Post #73 answers the question as asked. The question underneath it is different.
What I would check first on Metformin co-administration is whether the thing being measured moved or whether the way of measuring it moved. Those look identical in a graph.
The number people quote for Metformin co-administration is a central estimate presented without its interval, and the interval is wide enough that the estimate is nearly uninformative on its own.
SGLT2 inhibitors: frequently co-administered and relevant to renal and cardiovascular discussion, not to interactions. There is no pharmacokinetic interaction of concern.
Not a conclusion. A place to stand while looking for one.
Where I part company with post #77, and it is a narrow parting.
Metformin co-administration has a well-known answer and a correct answer, and the interesting work is establishing that they are the same. Nobody has done that here yet.
The documentation on Metformin co-administration is better than this thread and I say that as someone who has posted in the thread.
This follows post #78 rather than contradicting it.
A supplement is a drug for interaction purposes, and the fact that it is sold without a prescription tells you nothing about whether it interacts. The paperwork is usually worse rather than better.
The rule of thumb is fine; the edge cases are where it earns its keep.
Insulin and sulfonylureas are the interaction that the labelling in this class flags most explicitly, because the risk is additive glucose lowering. That is a prescribing question and not a forum question.
Small correction to my own earlier position on Metformin co-administration. I had the units the wrong way round, which changes the conclusion by an order of magnitude and therefore changes it entirely.
Picking up post #82: that is the part I would want checked first.
Metformin: commonly co-administered and relevant to gastrointestinal tolerability. Gastrointestinal side effects can overlap and additive. Taking them separately or adjusting one if tolerability is poor are reasonable approaches.
I have deliberately not rounded that, because the rounding is where the argument starts.
On post #84 — agreed on the reasoning, with one qualification.
A pharmacist can answer most questions in this subcategory in a few minutes with access to a proper interaction database, and that access is the thing a forum does not have.
That is the version I would defend. It is not the version I started with.
Adding the boring version of Metformin co-administration, because the interesting version keeps getting posted and the boring one is usually right.
Check the ordinary explanations, in order, and stop when one of them accounts for what you are seeing. Most of the time the second one does.