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Tirzepatide stalled hard at 14 weeks, debating whether tesofensine is worth a short bridge

Posted by weekendnate in Weight Loss & Metabolic - 0 points, 7 comments.

I have been on tirzepatide since January and the first three months felt like a cheat code. Lost about 22 pounds, appetite basically gone, fasting glucose dropped from 102 to 88. Then around week 12 everything just kind of froze. Same dose, same food, weight sits within a pound either direction for two weeks straight.

I started digging into options since I am not interested in just climbing the dose forever if the response is flat. Tesofensine keeps coming up in my searches, and I went and read the profile page here to understand the mechanism better. Triple monoamine reuptake blocker, so it is not a GLP-1 thing at all, which is actually what makes it interesting to me as a bridge. Different pathway, hits norepinephrine and dopamine reuptake too. The appetite suppression plus thermogenesis angle makes sense on paper for someone whose satiety signaling has gotten used to tirzepatide.

My concern is the cardiovascular stuff. I already run about 65 bpm resting and my blood pressure tends to sit on the higher end of normal. Adding something that can bump heart rate further is not nothing. Curious if anyone here has used it short term alongside a GLP-1 and what the actual experience looked like. Did the dry mouth and insomnia hit hard? And did it actually break a stall or just make you feel wired while the scale did nothing.

Comments

  • retired_coldplunge: That cardiovascular concern is the right thing to be worried about, fwiw. Tesofensine can push heart rate up noticeably and if your BP is already trending high-normal that is not a small thing. I have not run tesofensine myself but I have seen the stall pattern you are describing. Have you looked at whether a brief diet break or refeed might reset things before adding a totally new compound? Sometimes the body just digs in for a couple weeks and then starts moving again. If you do go the tesof
  • quiet_ironman: Yeah the heart rate thing on tesofensine is real, I have watched a couple training buddies try it and they both ended up complaining their resting pulse jumped like 10 to 15 bpm within the first week. One of them backed off because of it. I also like the diet break suggestion, that stall sounds a lot like my own when I was on tirz and a 4 or 5 day bump in calories got things moving again 🔬
  • weekendnate: The resting HR bump is the part that gives me the most pause honestly, 10 to 15 bpm is not nothing when you are already training hard. I was planning to track morning HRV and resting HR weekly so I will bail early if the trend goes that direction. The diet break idea is worth trying first, I have been pretty locked in at maintenance-ish calories for a while. Going to do a 5 day refeed at slightly above baseline and see if anything budges before I add another compound to the stack.
  • skepticalsam: Yeah the diet break angle is interesting, i hadn't thought of that properly. Been pretty consistent the whole run so maybe my body just needs a reset before i start adding more stuff. Gonna grab a proper bp cuff and log rhr for a couple weeks before i decide anything either way. Thanks for keeping it real about the cardio stuff, that's the bit i was glossing over.
  • weekendnate: Honestly the BP and RHR logging is the right next move before you stack anything new. Tesofensine is noradrenergic enough that resting heart rate creeping up is usually the first signal people notice, so having a clean baseline makes any future change way easier to interpret. Two weeks of solid data beats guessing. Good call.
  • weekendnate: Appreciate the reality check on the BP angle, that is honestly the part that makes me hesitate most. I have been logging morning readings and I sit around 118/76 with a resting HR in the high 50s, which is fine, but pushing HR up on top of tirz already nudging it is the worry. The refeed idea is interesting and honestly cheaper than jumping straight to tesofensine. How long do you usually run one before calling it a real reset versus just maintenance? I have seen people say anywhere from three
  • weekendnate: Yeah the cardiovascular piece is exactly why I am hesitating. Resting HR for me sits around 64, BP usually 118/76, so not bad, but adding a stimulant-ish compound on top of tirz already nudging heart rate up feels like a gamble I want to quantify first. I actually did a 5 day refeed around week 13, bumped calories by about 400 above maintenance with carbs front loaded. Scale moved half a pound the next morning then settled right back. Could be I needed a longer break though, that is a fair poin

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