In type 2 diabetes, you can use incretin-mimetic drugs to stimulate insulin secretion and mitigate glucagone release, slowing gastric emptying at the same time. Among these ones, exenatide (an agonist of glucagone-like peptide-1 ( GLP-1) receptors) needs one-two daily administrations, so a long-acting formulation is being studied, with a weekly administration. Sitagliptin (an inhibitor of dipeptidyl-peptidase-4) is based on a similar mechanism of action, slowing the degradation of endogenous GLP-1. This kind of drugs can represent therapeutical alternatives to sulfonylurea or to thiazolidinediones, when metformin alone is not capable to control diabetes. Some researchers have randomized 491 adults with type 2 diabetes (levels of HbA1c between 7.0% and 11.0%) under metforim therapy to add exenatide (2 mg subcutaneously in one weekly dose) or sitagliptin (100 mg daily) or pioglitazone (45 mg daily). Each subject has also received oral or injected placebo. After 26 weeks, exenatide has decreased the average levels of HbA1c more than pioglitazone and sitagliptin (-1.5% vs. -1.2% and -0.9%). Diabetics treated with weekly exenatide have also lost more body weight (-2.3 kg vs. -0.8 kg with sitagliptin and +2.8 kg with pioglitazone). There have been no important episodes of hypoglycemia, while the commonest side effects with exenatide and sitagliptin have been nausea and diarrhea. With pioglitazone, instead, infections of the upper airways and peripheral edemas have been more frequently recorded.
In a previous trial, exenatide in one weekly dose has been shown better than daily insulin glargine to obtain glycemia control and weight loss. With all probabilities, the weekly formulation is going to become a fundamental point in the therapy of type 2 diabetes.
