Specific antagonists for glucose-dependent insulinotropic polypeptide (GIP)

A pharmaceutical composition for treating a mammal in need of treatment to improve or normalize glucose tolerance and reduce weight or avoid unacceptable weight gain, said pharmaceutical composition comprising:

• a polypeptide antagonist comprising an amino acid sequence for binding to glucose-dependent insulinotropic polypeptide (GIP) receptors in the mammal for antagonizing the biological activity of GIP, said polypeptide antagonist when administered to a mammal in an amount effective (i) reduces intestinal uptake of postprandial glucose, (ii) reduces postprandial insulin release, (iii) decreases postprandial insulin blood levels and (iv) decreases postprandial glucose blood levels in the treated mammal, from those insulin and glucose blood levels normally attained in the mammal following a postprandial period when the mammal is untreated with said polypeptide antagonist, so that glucose tolerance is improved or normalized and reduced weight is achieved or unacceptable weight gain is avoided in the treated mammal, and
• a pharmaceutically acceptable excipient.

A method of developing a nonpeptide GIP antagonist comprising:

• using a GIP antagonist to identify characteristics of the GIP antagonist or the antagonist properties of a GIP antagonist;
• and
• developing a nonpeptide GIP antagonist which has characteristics similar to the GIP antagonist or antagonist properties of the GIP antagonist.

An isolated polypeptide comprising an amino acid sequence which specifically interferes with the biological activity of glucose-dependent insulinotropic polypeptide (GIP) when said polypeptide is administered to an animal in an amount effective to reduce intestinal uptake of glucose.