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In order to investigate whether exenatide could be used to stimulate glucose clearance and insulin secretion in alpacas without causing colic signs, six healthy adult alpacas were injected once a day with increasing subcutaneous doses. A follow-up intravenous glucose injection was given to induce hyperglycemia, and serial blood samples were collected to measure plasma concentrations of glucose, insulin, triglycerides, beta-hydroxybutyrate, and nonesterified fatty acids. The exenatide doses used were saline control (no drug), and 0.02, 0.05, or 0.1 mcg/kg injected subcutaneously. Alpacas had significantly lower plasma glucose concentrations and higher insulin concentrations on all treatment days compared with the control day, but the increase in insulin was significantly greater and lasted significantly longer when the alpacas received the two higher dosages. Two of the alpacas developed mild colic signs at the 0.05 mcg/kg dose and were not evaluated at the highest dose. Based on these findings, the 0.05 mcg/kg dose appears to offer the greatest stimulation of insulin secretion and glucose clearance without excessive risk or severity of complications.