Glucagon-like peptide-1 -related

Gutniak, M.K., Svartberg, J., Hellstrom, P.M. et al. (2001) Antidiabetogenic action of glucagon-like peptide-1 related to administration relative to meal intake in subjects with type 2 diabetes. Journal of Internal Medicine, 250, 81-87. 

There are other closely related DPP enzymes, such as DPP 8 and DPP 9. When these enzymes are inhibited in experimental animals multiorgan toxicity occurs. Sitaghptin appears to be highly selective for DPP IV and has 2600 times selectivity for DPP IV compared with DPP 8 and DPP9. Compared with placebo, sitaghptin produces an approximately two-fold increase in postprandial active glucagon-like peptide 1 concentrations (2). 

Several peptide products used in the treatment of diabetes mellitus, in addition to insulin, are currently administered by subcutaneous injection and these drugs are candidates for development of nasal formulations. Glucagon-like peptide-1 (GLP-l)-related peptides stimulate the insulin response to glucose and diminish the release of glucagon after a meal. These effects diminish the excessive postprandial increase in glucose observed after a meal in persons with type 2 diabetes mellitus. GLP-1-related peptides must be administered by subcutaneous injection before meals in order to be effective. This requirement for injection before each meal is likely to impact the utilization of these products by persons with type 2 diabetes. Exendin-4 is a GLP-1-related peptide with a molecular mass of 4.2 kDa. The development of a GLP-1-related peptide nasal formulation containing an absorption enhancer would allow patients to scll-administer one of these drugs just before a meal without the need for a subcutaneous injection. 

T.S. Haque, W.R. Ewing, C. Mapelli, V.G. Lee, R.B. Sulsky, D.J. Riexinger, R.L. Martinez, Y.Z. Zhu, Human glucagon-like-peptide-1 modulators and their use in the treatment of diabetes and related conditions, W02007,082,264. 

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