Nevertheless, GIP also has crucial further metabolic outcomes that GLP-one won't — significantly on adipose tissue. GIP receptors are highly expressed in Body fat tissue, and GIP appears to Perform a task in regulating Excess fat storage and fatty acid metabolism.
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The synergy of GIP and GLP-one receptor co-activation describes why tirzepatide constantly outperforms single GLP-one agonists in scientific endpoints. While in the SURPASS-2 head-to-head trial vs semaglutide 1mg, tirzepatide at 10mg and 15mg produced statistically noticeably larger HbA1c reductions and human body fat loss.
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GLP-one receptor agonists like semaglutide exploit these results pharmacologically — at drug doses, they produce sustained GLP-1 receptor activation with clinically meaningful reductions in HbA1c and human body weight.
Lilly’s insight was that GIP receptor agonism (as an alternative to just endogenous GIP signalling) might defeat this resistance and add metabolic Rewards complementary to GLP-one agonism.