MK-0893, developed by Merck, is a reversible and competitive antagonist with high binding affinity (IC(50) of 6.6 nM) and functional cAMP activity (IC(50) of 15.7 nM). MK-0893 reached Phase 2; 12 weeks of once daily oral dosing led to significant and dose-dependent reductions in fasting and post-prandial plasma glucose and in HbA1c, with similar low incidences of hypoglycaemia as a metformin cohort. Combinations with metformin and sitagliptin were also trialled, and risk for hypoglycaemia was assessed in healthy males which showed the drug caused lengthening of recovery times. However, plasma levels of LDL cholesterol and liver transaminases were increased in some studies, as was body weight and blood pressure, all of which were not evident pre-clinically, and MK-0893 was discontinued.