GIP hormone: the second hormone behind Mounjaro

The GIP hormone is a gut hormone released after a meal that prompts your pancreas to make insulin. The abbreviation stands for glucose-dependent insulinotropic polypeptide. Together with GLP-1 it forms the incretin group: hormones that warn your body food is on its way.

Mounjaro mimics both hormones. Ozempic and Wegovy mimic only one.

That single difference explains most of the gap in results between the two drugs, and it also explains why the blood values respond slightly differently.

What does the GIP hormone actually do?

It governs your insulin response to food and steers how your fat tissue handles that insulin. GIP is released in your small intestine as soon as food arrives, well before your blood sugar has genuinely risen. Your pancreas therefore gets advance warning instead of a correction after the fact.

Researchers call that the incretin effect.

It is why the same quantity of glucose taken by mouth produces a far larger insulin response than the same amount through a drip. Your gut has a say. In type 2 diabetes that exact effect is blunted, which is one reason these drugs work so well there.

What is the difference between GIP and GLP-1?

GLP-1 works mainly on appetite and on how fast your stomach empties. GIP additionally acts more strongly on fat tissue and on how sensitive that tissue is to insulin. They overlap on the insulin response and differ on almost everything around it.

That both hormones only trigger insulin when blood sugar is high is the safety valve. It is why these drugs on their own rarely cause a low blood sugar, unlike insulin or a sulfonylurea.

Why does a drug acting on two hormones work better?

Because the two routes complement each other rather than duplicating. Tirzepatide is not simply two drugs in one syringe: it binds the GIP receptor more strongly than the GLP-1 receptor and activates those routes unevenly too (Willard et al., 2020).

Researchers call that an imbalanced, biased agonist.

It sounds like a shortcoming and is probably the whole point. In SURPASS-2, which put tirzepatide directly against semaglutide, HbA1c fell 2.30 percentage points on the highest dose against 1.86 with semaglutide, and weight fell a further 5.5 kilos (Frías et al., 2021).

In people without diabetes, tirzepatide reached up to 20.9% weight loss over 72 weeks in SURMOUNT-1 (Jastreboff et al., 2022). The full comparison between the two drugs is in Ozempic or Mounjaro.

What else do hunger and satiety hormones do?

Between them they decide when you get hungry and when you stop eating. Ghrelin is the best known hunger hormone and rises before a meal. The incretins pull the other way and belong to the satiety side. Neither is a switch you can flip yourself.

The slowed stomach emptying is the most noticeable effect of the set.

Your stomach stays full longer, so the feeling of fullness lasts longer. That is simultaneously why nausea is the most reported complaint on these drugs. The desired effect and the most unpleasant side effect come out of the same mechanism.

Which complaints go with it is covered in Ozempic side effects.

Can you have the GIP hormone measured?

In practice, no. GIP is not offered as a routine determination by Dutch laboratories, and a standalone GIP value would tell you little anyway. The hormone swings sharply around meals and there is no usable reference range for everyday use.

That is more honest than it sounds.

What you do measure is the result of what GIP and GLP-1 do together. Your fasting glucose shows where you are starting, your fasting insulin shows how hard your pancreas is working to get there, and your HbA1c summarises the last three months.

Two people both have a fasting glucose of 6.2 mmol/l. The first has a fasting insulin of 6 mU/l, the second 22 mU/l. Same blood sugar, but the second pancreas is doing almost four times the work to hold it there. That second person sits far closer to type 2 diabetes, and you only see it if you measure the insulin alongside.

Those three together say more about your incretin system than any single hormone value would. The GLP-1 extended check contains all three, assessed by a BIG-registered doctor.

Why this is more than trivia

Because it decides which drug suits which situation. Someone whose problem is mainly appetite already gets a great deal from the GLP-1 route alone. Someone with pronounced insulin insensitivity may get more from the dual route, though that is a judgement for your doctor rather than for you alone.

According to the Dutch RIVM, over a million people in the Netherlands live with diabetes, the large majority of them type 2.

What strikes me about GIP is how long it was written off as the boring incretin. For twenty years GLP-1 was the interesting hormone and GIP the supporting act. Tirzepatide reversed that order.

Have your glucose, insulin and HbA1c measured together before you start a course, and you will know which side of this system weighs heaviest for you. What it means if you already have type 2 diabetes is covered in losing weight with type 2 diabetes.

References

• Willard FS et al. Tirzepatide is an imbalanced and biased dual GIP and GLP-1 receptor agonist. JCI Insight. 2020. PMID 32730231
• Frías JP et al. Tirzepatide versus Semaglutide Once Weekly in Patients with Type 2 Diabetes (SURPASS-2). N Engl J Med. 2021. PMID 34170647
• Jastreboff AM et al. Tirzepatide Once Weekly for the Treatment of Obesity (SURMOUNT-1). N Engl J Med. 2022. PMID 35658024
• Farmacotherapeutisch Kompas, tirzepatide monograph (mechanism of action).
• RIVM, figures on diabetes in the Netherlands.
• Thuisarts, information on type 2 diabetes and blood sugar.

Every blood test result includes a professional assessment from a BIG-registered doctor. Discuss your result with your GP before changing anything about your treatment.