CommunityNews & Policy

Study: Do Fasting GLP-1 and GIP Levels Predict the Initial Pharmacological Response to Semaglutide and Tirzepatide?

8 replies6 peopleJul 16, 2026☆ Follow
Summary

Do baseline fasting GLP-1 and GIP levels predict how well people respond to semaglutide or tirzepatide?

The thread discusses a small study finding that low baseline GIP favors tirzepatide while low GLP-1 with higher GIP favors semaglutide, with high levels of both linked to poor response from either drug. Participants note the results align with the drugs' different receptor affinities but find some combinatorial outcomes surprising and hard to explain. Several stress the findings are preliminary and require larger validation before any clinical use.

What this discussion establishesWhere people disagree

Whether tirzepatide truly acts independently of GLP-1 levels or still needs some functional GIP signaling to work well

Still open

What hidden factors explain the low/low responder group and whether the proposed decision rules hold up in larger trials

Nothing here is advice.

8 replies · 6 people
PatientHarbour61archiveopening postJul 16

I came across research exploring if initial fasting measurements for GLP-1 and GIP could indicate how individuals might respond to those two treatments, and apparently they could. This points to the possibility that the medications work better with lower natural hormone amounts, which could mean higher receptor responsiveness, whereas higher natural amounts might lead to less impact because of reduced receptor responsiveness. It didn't shock me that one surpassed the other across multiple measures, yet finding the reverse in additional measures caught me off guard. Looking closer though, other findings stood out too, such as unexpected wins for one in certain phases over others, along with its strongest outcome in a phase where the alternative had one of its weaker ones, and these gaps weren't minor.

PatientHarbour61archiveJul 16

I came up with a better graph than the last one we looked at.

SteadySignal69archiveJul 16

It seems logical that sema doesn't depend much on GIP and tends to work better only with reduced GLP-1 levels. Yet ending up with low readings on both counts comes across as puzzling and illogical, implying some unknown element must be shaping the outcome. Tirz looks like it operates without needing GLP-1 while instead relying on reduced GIP, and this pattern holds steady in observations. Still, its not also needing reduced GLP-1 the way sema does doesn't align easily with its makeup. This is quite odd.

GreyAlder39archiveJul 16

The main point they highlight is a suggested way to pick one med or the other depending on those hormone readings, yet they make clear it is only an idea worth checking later and not something ready for everyday medical use before larger trials back it up. I found the paper refreshingly open about how they handled the numbers despite the limited group size plus how they spelled out where the findings fall short. Everything matches what we know about how the compounds attach to the receptors in distinct ways plus the uneven signaling pattern of the first one.

PatientFenwick91archiveJul 16

I figure this company aims to market a hormone assay meant to guide which weight loss drug to pick and dodge useless ones. Anyone can see that low GLP-1 plus high GIP points to strong results from semaglutide. The paper lays out simple matching rules from the nine possible combinations. Low GIP on its own favors the dual agonist for the biggest drop. Low GLP-1 paired with middle or high GIP favors the single agonist for the same big drop. Both hormones high means weak effects from either so other paths like combined meds surgery or new non gut hormone options make more sense. Everything else gives mixed outcomes so other details decide. All it needs is one early morning blood draw plus two standard lab tests so it fits right into normal visits. That lab work adds very little next to half a year on the medicines and might cut wasted time plus failed tries. One of the writers held a post at the firm while the rest stated no money links that could bias things.

GreenMeadow54archiveJul 16

I believe this pattern applies to the majority of these compounds. For most, responses break down into roughly equal groups: one where folks report strong results, another with mild or uncertain benefits, and one seeing zero change. This variation seems tied to personal physiology rather than the substance. Starting from a deficit in the targeted area leads to noticeable shifts, whereas beginning at higher levels yields minimal impact. That variability also contributes to the challenges in researching and confirming their value, since solid conclusions would require matching participants by genetic makeup and initial measurements.

GreyAlder39archiveJul 16
↳ replying to @GreenMeadow54

Various mutations produce distinct binding strengths at the trio of receptors linked to Reta. A handful of those shifts stand out sharply, for example one swap cut the substance strength by 107.7 times.

KeenKettle50archiveJul 16

I find that research quite interesting. Once other groups replicate the results, testing my starting amounts of those hormones might clarify if the drugs are a good option.

PatientHarbour61archiveJul 16
↳ replying to @SteadySignal69

I have a guess about why that disappointing outcome showed up. Using just one of those medications probably isn't something that stands apart from the other hormone. It seems to depend on having decent levels of the second one present to get any real effect. That notion might connect to some earlier lab findings I came across once, where the second hormone appeared to heighten how responsive the receptors for the first one are inside certain brain regions. When both sit at low readings, it looks like you have to go after the pair at once, since sorting out the second one clears the way for the first one to land properly.

Add your experience

If you have tried it, this topic is still open. Sign in to reply — it takes a minute.

Study: Do Fasting GLP-1 and GIP Levels Predict the Initial Pharmacological Response to Semaglutide and Tirzepatide? · ZyraTrack Community