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Treatment of Type 2 Diabetes Mellitus: A Weighty Enigma
Successful treatment of the central clinical issues in type 2 diabetes—hyperglycemia and obesity—is difficult, elusive, and often enigmatic. Lifestyle change is difficult, and most pharmacologic treatment options cause weight gain. Faced with an obese patient with failing glucose control, clinicians must decide whether a further reduction in average glucose level by 10 mg/dL to 20 mg/dL is worth another 10 pounds of weight gain. Why do we find ourselves facing this therapeutic dilemma? First, our knowledge of the pathophysiology of type 2 diabetes is largely descriptive rather than mechanistic. We know about insulin resistance and defective insulin secretion, but we do not understand their causes in enough depth to target the defects precisely. Second, poor lifestyle choices continue to undo the benefits of our treatments. Sustaining the changes in behavior that are required to improve diet and exercise is exceedingly difficult for patients.
Two studies in this issue describe exciting new approaches—incretins (1) and inhaled insulins (2)—that directly address this context. Incretins are a new class of medication that target the subtle web of hormonal and neuronal responses to nutrition (3). Glucagon-like peptide-1 coordinates glucagon and insulin release with the transit of food though the stomach and intestine (4). Exendin-4 (exanatide) mimics glucagon-like peptide-1 and has good pharmacokinetic properties for clinical use (5). Agents like exanatide are peptides, so they require injection, which most patients don't like (6). Inhaled insulin offers a new mode of insulin delivery that seems to increase its rapidity of onset and prolong its action (7, 8). Because of their pharmacologic properties, both incretins and inhaled insulin aim to control meal-associated glycemia, a frequent cause of failure to achieve glucose control targets (9).
In this issue, Heine and colleagues …
