Impact of improving postprandial glycemic control with intensifying insulin therapy in type 2 diabetes

ABSTRACT

Worldwide, many people with type 2 diabetes are not at recommended glycemic targets and remain at increased risk of microvascular and macrovascular complications. Reaching recommended glycemic targets requires normalizing both fasting and postprandial glucose (PPG). For some patients, this will require addition of a prandial insulin delivered by injection to control PPG excursions. Evidence from epidemiological studies suggests an association between postprandial hyperglycemia and cardiovascular disease, and thus, expert guidelines recommend that treatment for elevated PPG not be delayed. Indeed, studies have demonstrated that PPG makes the greatest contribution to HbA_1c in patients who are approaching, but have not yet reached HbA_1c <7.0%.

Appropriately timed exposure of the liver to insulin is critical in suppressing hepatic glucose output (and therefore PPG levels) after a meal. Rapid-acting insulin analogs, with their faster onset and shorter duration of action, offer advantages over regular human insulin. Unfortunately, even with improved pharmacokinetic/pharmacodynamic characteristics, rapid-acting insulin analogs are still unable to fully reproduce the rapid release of insulin into the portal circulation and suppression of hepatic glucose output that occurs in the individual without diabetes after starting a meal. The next generation of rapid-acting insulin analogs will have an even more favorable pharmacokinetic profile that should allow patients to further improve glycemic control. Continuous subcutaneous insulin infusion (CSII) represents another option for intensifying therapy and improving postprandial control in some patients, and studies have shown that the benefits are sustainable long-term. However, it is currently unclear which patients stand to benefit the most from the extra expense and complexity of a CSII regimen, and further studies are needed.

KEYWORDS:

• Basal–bolus therapy
• insulin
• insulin analogs
• treatment intensification
• type 2 diabetes

Declaration of interest

Medical writing and submission support were provided by Gary Patronek, Helen Parker, and Grant Womack of Watermeadow Medical, an Ashfield company, part of UDG Healthcare plc, funded by Novo Nordisk. Novo Nordisk also reviewed the manuscript for medical accuracy. The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Additional information

Funding

This work was supported by Novo Nordisk.