Exenatide in Combination Therapy: Small Study, Big Market, and Many Unanswered Questions

In the past decade, many new medications have improvedour ability to treat patients with type 2 diabetes (1). The pharmaceutical industry has played a key role in this pro-cess. Among these novel medications are newly designed insulins, thiazolidinediones (TZDs), meglitinides, orally active inhibitors of the incretin-degrading enzyme dipepti-dyl peptidase-IV, and glucagon-like peptide (GLP) mimet-ics. Combinations of these drugs, each drug with its dis-tinct pharmacologic mechanism of action, have increased our capacity to manage patients with diabetes. The latter 2 drug classes mentioned enhance or mimic the effects of endogenous incretins, such as GLP hormones secreted by the gut (2–4). As with most gut peptides, GLP biological activity is exercised locally by inhibiting gastric emptying but also in the pancreas by stimulating glucose-dependent insulin secretion, promoting insulin biosynthe