Retatrutide, Rapamyacin & Metformin - anyone combining? Any issues or synergies?

I’ve started Retatrutide, going ‘low and slow’ in the hopes of reducing my visceral belly fat. Meanwhile I stopped my low dose Rapamyacin / Metformin. I was getting mouth sores every couple of months which was annoying and I didn’t want to jinx the Retatrutide. However I’m a female ~60 yr. and females are know for their autoimmune issues as we age. I want to keep any current or future inflammation issues in check.

Has anyone tried combining the two? Retatrutide & Rapamyacin? Or the three? Retatrutide & Rapamyacin & Metformin?

2 Likes

Good news, you can ditch metformin since you’re taking a GLP1 agonist.

Since rapamycin elevates my blood glucose, pairing it with retatrutide has worked out well for me, and I don’t have to worry about elevated glucose or borerline high A1c anymore. No side effects from this combination in my case.

4 Likes

59 yo woman here…

8mg of rapa each week and on low dose Reta… no issues at all

.5 crp and low A1c (even without the drugs).
I have hashimotos that is no worse or better since starting.

When I turned approx 50, I could no longer handle gluten… after I started rapa, related or not, my sensitivity disappeared

All this is to say, based on my N=1, I would not worry in the least about being a 60yo woman and taking these things together. They might negatively affect you, but I don’t personally believe being a woman is related. Take anything I say with a grain of salt!

Btw, I used to take metformin for my high glucose spikes, but it didn’t control them very well. Since being here, I’ve switched to dapagliflozin and Acarbose which help me significantly more… because my A1c was already good, there has not been much of an effect there.

2 Likes

I take Retatrutide and Rapamycin. I don’t take metformin because the longevity data is not good and I don’t have T2D but I do take Acarbose instead.

2 Likes

Yes — I’m currently running that exact combo.

I’ve been on retatrutide 12 mg weekly for about a year, along with rapamycin once per week and metformin XR 500 mg daily.

Mechanistically it makes sense since they all hit different pathways:

• Retatrutide → GLP-1 / GIP / Glucagon metabolic signaling

• Rapamycin → mTOR inhibition (autophagy / longevity pathway)

• Metformin → AMPK activation and improved insulin sensitivity

In theory you’re covering three major metabolic/aging pathways at once. The main thing to watch is appetite suppression and making sure calories and protein stay high enough to avoid muscle loss.

Obviously still very experimental since there are no clinical trials on this stack, but from a pathway perspective the combination is interesting.

Curious if anyone else here has run the same stack and what their experience has been.

2 Likes

I’m taking 1 mg Reta on Monday evenings and 6 mg Rapa Friday evenings. 65F. Tested giving up the Rapa and oof joints hurt, have osteoarthritis in my hands that I’m hoping will improve. No weight issues. Hoping the Reta helps lower my A1C from 5,6 (despite low carb for years and hypoglycaemia if I work out late afternoon) and slow progression of the OA.

1 Like

48 year old male here. 2mg Reta microdosed weekly, 6mg weekly of Rapa, and 500mg (twice daily) XR Metformin. Last A1C was 4.2. No issues on that stack at all. I hope that helps.

Why not using Tirz instead of Reta, since glucagon will raise your RHR?