Has anyone dealt with semaglutide pharmacokinetics?

One more consideration: if you ever come off semaglutide (insurance issues, supply problems, side effects), the metformin is your safety net. It's keeping hepatic glucose output in check independently. Dropping metformin AND then potentially losing sema access would leave you with no pharmacological glycemic control. Belt AND suspenders.

I have a related question — I'm NOT diabetic, I'm on sema purely for weight loss. My telehealth provider offered to add metformin for "metabolic optimization." Is there any benefit to metformin in a non-diabetic person already on sema?

This is more controversial. There's no FDA-approved indication for metformin in non-diabetic individuals. Some clinicians prescribe it off-label for weight management or "longevity" based on observational data and the ongoing TAME trial premise.

The evidence for added weight loss from metformin in non-diabetic people already on semaglutide is weak — maybe 1-2 kg additional loss at best. The "metabolic optimization" framing is vague and not strongly evidence-based in your context.

That said, metformin is extremely safe and cheap. It's not going to hurt you. But I wouldn't take on additional GI side effects for marginal benefit when semaglutide is already doing the heavy lifting. Personal opinion though — discuss with your provider.

Great thread. The answer seems clear for T2DM patients: keep both. For non-diabetics: probably not worth adding. Simple enough. Thanks everyone 👏