SOURCE: Aronoff SL. Rationale for treatment options for mealtime glucose control in patients with type 2 diabetes. Postgraduate Med 2017;129:231-241.
The philosophy of “fix the fasting first” seems both physiologically and functionally sound when initially addressing elevated A1c levels, since the greatest burden of excess glucose in most patients with A1c levels > 8 is from fasting and overnight glucose load (rather than postprandial). Once the fasting glucose has been corrected, if the A1c is not at goal postprandial glucose (PPG), excesses then must be addressed with treatments that preferentially reduce PPG.
Several classes of agents are appropriate to address PPG elevations, including alpha-glucosidase inhibitors, glinides (e.g., nateglinide, repaglinide), rapid-acting insulin, GLP-1 receptor agonists (e.g., exenatide, liraglutide, albiglutide), and pramlintide. Pramlintide is a parenteral analogue of the hormone amylin, which is co-secreted with insulin by beta-cells. In addition to facilitating insulin activity, pramlintide also demonstrates some GLP-1 receptor agonist-like activity (e.g., delayed gastric emptying, although through a hypothalamic mechanism rather than gastrointestinal mechanism).
Recent exploration of the GLP-1 receptor agonist class has suggested that it may be subclassified into short-acting and long-acting agents. Although all currently available GLP-1 receptor agonists affect both fasting and PPG, short-acting GLP-1 receptor agonist agents (exenatide and lixisenatide) appear to produce a more dominant effect on PPG, whereas the so-called long-acting GLP-1 receptor agonists produce a more dominant effect on fasting glucose.
Control of PPG sometimes is critical to attain A1c goals; additionally, there has been some literature support for an association between elevated PPG and adverse cardiovascular outcomes. Fortunately, there is a diversity of good choices available to address PPG elevations.
The philosophy of 'fix the fasting first' seems both physiologically and functionally sound when initially addressing elevated A1c levels.
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