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Glucagon\u2010like peptide\u20101 (GLP\u20101) receptor agonists provide a new pharmacotherapeutic option based on the multiple glucose\u2010lowering effects of the human hormone GLP\u20101. This mechanism of action not only provides therapeutic efficacy but also suggests that GLP\u20101 receptor agonists have distinct safety and tolerability concerns compared with other diabetes therapies. Stimulation of pancreatic insulin secretion by GLP\u20101 receptor agonists is glucose dependent, conferring a lesser risk of hypoglycaemia than that seen with sulfonylureas. Individual GLP\u20101 receptor agonists differ in their metabolism and excretion profiles, affecting the choice of agent for patients with renal impairment. As with other protein\u2010based therapies, GLP\u20101 receptor agonists may induce the formation of antibodies that may attenuate therapeutic efficacy and affect safety. Conclusions on cardiovascular safety must await outcomes studies, but at present no signal of harm has been reported, and preclinical data and effects on risk markers suggest a potential for benefit. Current data on thyroid medullary cancer in humans and pancreatic malignancy in rodents do not suggest that there is any reason to restrict the clinical use of GLP\u20101 analogues in most people with diabetes. It is currently difficult to ascertain the possible contributory role of GLP\u20101 receptor agonists in increasing the risk of pancreatitis, and vigilance for signs and symptoms is prudent. Primary tolerability issues include transient gastrointestinal symptoms, common with GLP\u20101 receptor agonists, which can be reduced through dose titration. 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