SURMOUNT-5: Tirzepatide vs semaglutide head-to-head — November 2025

Welcome to the tirz side! 😊 I made the exact same switch about 8 months ago. Was on Wegovy 1.7mg, stalled for 3 months, switched to Mounjaro.

The first couple weeks at 2.5mg felt almost... too easy? Like the dose was way too low compared to what I was on. But my endo said to be patient and follow the titration schedule. She was right — once I hit 7.5mg, the appetite suppression was NOTICEABLY different than what I'd experienced on sema. It's hard to explain but it feels more... complete? Like sema killed my hunger but tirz kills hunger AND somehow changes how food interests me.

The dual agonism (GIP + GLP-1) really does hit different. I've lost an additional 31 lbs since switching.

One heads up — sulfur burps might be a new thing for you. I never had them on sema but they showed up around week 3 on tirz. Manageable though.

Endocrinologist here. Your physician's approach is reasonable — the direct switch without a washout is standard practice and supported by clinical experience, though there isn't a specific trial protocol for sema→tirz switching.

A few clinical notes for context:

1. Starting at 2.5mg tirz after being on 2.4mg semaglutide will feel like a step down in GLP-1 receptor activation. This is expected and temporary.
2. The SURPASS and SURMOUNT data showed tirzepatide's weight loss continues to separate from semaglutide at higher doses — the 10mg and 15mg doses in SURMOUNT-5 showed ~5-7% greater weight reduction vs semaglutide 2.4mg.
3. Your improved fasting insulin is encouraging. Tirzepatide has demonstrated superior insulin sensitization compared to semaglutide in head-to-head data, likely due to the GIP component's effects on adipose tissue.

I'd recommend following the standard 4-week titration at each dose level. Resist the temptation to accelerate — the GIP receptor needs time to upregulate.

— Board-certified endocrinologist, opinions are not medical advice

anders_CPH said:

Endocrinologist here. Your physician's approach is reasonable — the direct switch without a washout is standard practice and supported by clinical exp…

Thank you for that explanation! Quick question — my endo mentioned potentially going faster through 2.5 and 5mg since I was already on a high sema dose. Would doing 2 weeks at 2.5 and 2 weeks at 5 before settling at 7.5 be risky?

Not the previous poster but I'm a pharmacist who sees a LOT of these switches. Accelerated titration from sema is pretty common in practice. The main risk is GI side effects, and since you already have established GLP-1 receptor tolerance, 2 weeks at each starter dose is generally well-tolerated.

That said — follow YOUR doctor's guidance, not the internet's. 😄