Individualizing Treatment of Hyperglycemia in Type 2 Diabetes

The older agents, metformin and the sulfonylureas, are available for a cash (no insurance) price of as little as $4 per month. This is in stark contrast to the SGLT-2 inhibitors, GLP-1 receptor agonists, and DPP-4 inhibitors, which range in cost between $400 and $600 per month. Of recent concern, the cost of insulin has been skyrocketing, with a more than 500% increase in the cost of certain insulins from 2001 to 2015 [93]. According to the Medical Expenditure Panel Survey (MEPS) from 2002 to 2013, the mean price of insulin increased by about 200% (from $4.34/mL to $12.92/mL) during this period, which was significantly higher than increases in the price of non-insulin comparators [94]. The introduction of biosimilar insulins to the market is expected to offer treatment options with lower cost. This will be tested when the biosimilar glargine, the first FDA-approved biosimilar insulin, becomes available in the U.S. market. However, a significant reduction in insulin prices is not expected soon [95].

When insulin is required, most patients with T2DM can be treated with older human insulins, which have similar efficacy and lower costs than the more expensive newer insulin analogs. A Cochrane review comparing basal insulin analogs to NPH showed similar efficacy in glycemic control with minimal clinical benefit in the form of less nocturnal hypoglycemia in the insulin analog arm [96]. Furthermore, similar glycemic control and risk of hypoglycemia was seen when regular insulin was compared with the rapid-acting insulin analogs [97]. The cost of human NPH insulin for a patient on a total daily dose of 60 units is approximately $52 per month. This contrasts with the most widely used insulin, insulin glargine, which has a cash price of about $500 per month for the same amount (Table 5). Insulin pens, which are convenient, are more expensive. Interestingly, human insulins do not require prescriptions, allowing underinsured, underfunded patients ongoing access to them.

Incorporating Patient Preferences

Research evidence is necessary but insufficient for making patient care decisions. Along with the potential benefits, harms, costs, and inconveniences of the management options, patient perspectives, beliefs, expectations, and health-related goals must be considered. Patients will undoubtedly have preferences regarding defining goals and ranking options. Clinicians should discuss therapeutic goals and treatment options and work collaboratively with patients in determining management strategies [98].

Summary

Potential treatment approaches for treating hyperglycemia in T2DM are summarized in Figure 1 and Figure 2 [4,7]. As long as there are no contraindications, metformin should be recommended concurrent with lifestyle intervention at the time of diabetes diagnosis. Even if metformin monotherapy is initially effective, glycemic control is likely to deteriorate over time due to progressive loss of β-cell function in T2DM.

There is no consensus as to what the second-line agent should be. Selection of a second agent should be made based on potential advantages and disadvantages of each agent for any given patient. A patient-centered approach is preferred over a fixed algorithm. If the patient progresses to the point where dual therapy does not provide adequate control, either a third non-insulin agent or insulin can be added. In patients with modestly elevated A1C (below ~8%), addition of a third non-insulin agent may be equally effective as (but more expensive than) addition of insulin.