The therapeutic potential of somatostatin receptor ligands in the treatment of obesity and diabetes.

Since the development of synthetic somatostatin analogues, several therapeutic applications for somatostatin receptor agonist molecules have been defined. Established applications for somatostatin analogue treatment include pituitary tumours (growth hormone and thyrotropin-secreting adenomas), neuroendocrine tumours of the pancreas and gastrointestinal tract (so-called carcinoid tumours, vasoactive intestinal tumours) and gastroenterological conditions (pancreatitis, gastrointestinal bleedings, refractory diarrhoeas, pancreatic and intestinal fistulas, diarrhoea in AIDS). Further areas for development of somatostatin analogue therapy include obesity, polycystic ovary syndrome and diabetes mellitus, dysmetabolic conditions that are often interrelated. The challenge for the future will be to transform results from clinical trials conducted in heterogeneous clinical situations into novel options of somatostatin analogue use. Since obesity and diabetes mellitus both are disorders of marked heterogeneity, the subgroup of patients that will benefit most from somatostatin analogue treatment has yet to be defined. In addition, the development of more universal ligands covering all of the known somatostatin receptor molecules as well as receptor subtype specific agents is currently underway. The establishment of slow-release depot formulations of octreotide and lanreotide has already provided a more acceptable and consistent delivery mechanism. Use of biodegradable polymer microsphere formulations provides the basis for the development of novel applications, which include hyperinsulinaemia, obesity and polycystic ovary syndrome as components of the dysmetabolic syndrome. The most developed thus far is the use of octreotide in hyperinsulinaemic forms of obesity and in distinct stages of diabetic retinopathy.