Somatostatin analogs as glucagon suppressants in diabetes

Somatostatin, an inhibitor of glucagon secretion, has been tested experimentally to evaluate its therapeutic potential in the treatment of juvenile onset diabetics (Meissner, Thum, Beischer, Winkler, Schroder, and Pfeiffer 1975; Gerich, Lorenzi, Schneider, Karam, Rivier, Guillemin and Forsham 1974). However, the potential therapeutic value of somatostatin is limited by the fact that it is relatively ineffective when injected subcutaneously and must be given by continuous intravenous infusion. The present study was designed to identify analogs that might be more effective than somatostatin upon subcutaneous adminstration. The three analogs selected for the study were [D-Trp⁸]-SS, [D-Trp⁸-D-Cys¹⁴]-SS and [D-Cys¹⁴]-SS. The study reveals that two analogs, [D-Trp⁸]-SS and [D-Trp⁸-D-Cys¹⁴]-SS, have a more prolonged action in inhibiting glucagon secretion than unmodified somatostatin when injected subcutaneously, indicating that they might prove to be more useful therapeutically than somatostatin in controlling the hyperglycemia of human diabetics. No overt clinical evidence of untoward side effects, such as steatorrhea or weight loss, was observed in any dog during and after the three days of treatment with either analog as might be expected considering the inhibitory actions of unmodified somatostatin upon gastrointestinal functions. The data obtained in this study suggest that these analogs may have potential therapeutic usefulness in human juvenile-onset diabetics.