27 Cardiovascular disease is the leading cause of death in both dialysis and transplant patients, and current evidence suggests caution with the use of both agents but favours the utilization of pioglitazone if a PPARγ agonist was desired. These agents, which include acarbose, miglitol and voglibose, are enzyme inhibitors that act in the intestines to attenuate the absorption of carbohydrates. Acarbose has been shown to reduce HbA1c by approximately 0.8% in type 2 diabetics,3 although the increased delivery of carbohydrates into the colon means gastrointestinal side effects are very Cobimetinib concentration common and include flatulence,

bloating, abdominal pain and diarrhoea. This severely limits the utility of these agents as between 24% and 45% of patients will discontinue these agents.3,28 In the context of renal impairment, acarbose is not recommended for use in individuals with an eGFR less than 25 mL/min, although it is often overlooked for any degree of renal insufficiency. Its use in kidney transplant recipients is also likely to be prohibited as its concomitant use with mycophenolate mofetil could trigger gastrointestinal upset. The meglitinides, repaglinide and netaglinide, are short-acting CP-673451 agents that close the ATP-dependent

potassium channel on cell membranes of the pancreatic beta cell in a similar fashion to sulphonylureas, MG-132 cost resulting in depolarization of cells and subsequent calcium influx inducing insulin secretion. By administration pre-meals, it reduces postprandial glycaemia and is associated with HbA1c reductions of up to 2.1% (repaglinide > netaglinide).29 Side effects of the meglitinides include hypoglycaemia and weight gain, with gastrointestinal

symptoms rare. One of the significant advantages of meglitinides is the safe administration of these agents in the context of even severe renal impairment (repaglinide > netaglinide), as these drugs undergo hepatic clearance. To this effect, repaglinide is one of the only drugs shown to be safe (minimal interaction with immunosuppression) and efficacious (HbA1c lowering) post-transplantation30 and is considered the first-line agent for use in the context of new onset diabetes after transplantation.2 The two main gut hormones (or incretins) are glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP), secreted by K cells in the upper small intestines. Gut hormones have been shown to have an important role in whole-body glucose homeostasis by suppressing meal-related glucagon secretion, delay gastric emptying and induce satiety,31 with GLP-1 having greater potency than GIP.