Clinical Review

Individualizing Treatment of Hyperglycemia in Type 2 Diabetes


 

References

Another class with potential cardiovascular benefits is the SGLT-2 inhibitors. In a recent cardiovascular outcome study, empagliflozin significantly lowered the composite of cardiovascular death, nonfatal MI, or nonfatal stroke in T2DM patients with high cardiovascular risk compared to placebo (10.5% and 12.1%, respectively) [86]. There are several large ongoing studies evaluating the cardiovascular effects of other SGLT-2 inhibitors [87–89].

DPP-4 inhibitors were examined in recent studies and have shown no cardiovascular benefits [42,44,90].The studies showed mixed results regarding an association between DPP-4 inhibitors and heart failure. In one study, saxagliptin was associated with increased hospitalization for heart failure compared to placebo [44], while 2 noninferiority trials did not show a significant increase in heart failure hospitalizations associated with alogliptin and sitagliptin when compared to placebo [42,90].

Administration Considerations

Many patients with T2DM require multiple agents for glycemic control. Additional medications used for comorbid conditions add to this burden. When choosing antihyperglycemic agents, the route and frequency of administration, as well as the patients’ preferences and ability, should be considered. Either once or twice daily dosing is available for most agents, and once weekly dosing is available for some of the GLP-1 receptor agonists. Once daily or once weekly formulations may improve adherence and be more desirable than preparations that are dosed twice daily. Most of the commonly used medications are dosed orally. Although many patients find this route of administration preferable to insulin or GLP-1 receptor agonists, which require injections, some patients may prefer the risk/benefit of injectable agents. All GLP-1 receptor agonists come in a pen delivery system, which eliminates mixing and provides more convenient administration. Extended-release exenatide also is available as a single-dose tray that requires mixing and may be more cumbersome to inject.

Insulin requires special consideration. There has been an enormous increase in the number of insulin products on the market in the past 2 decades. These products include insulin analogs, concentrated insulins (U-200, U-300, and U-500), premixed insulin preparations, and ultra-long-acting insulin [91]. The availability of insulin options with different concentrations, onsets, and durations of actions has made decision making on which insulin to use difficult. Clinicians need to consider patient preference, dosing frequency, and timing with regard to meals, insulin dose, administration, as well as cost. For example, concentrated insulin is preferred for a patient on high doses of insulin requiring injecting a large volume of insulin. Rapid-acting insulin analogs would be more appropriate for patients who have difficulty administering their regular insulin 20 to 30 minutes before eating. Premixed insulin preparations make it impossible to independently adjust short- and long-acting components. However, these may be good choices in patients who have consistent meal schedules and who want to simplify administration. Despite a prevailing misconception that NPH must be given twice a day, it has long been recognized that in T2DM, a single daily injection of NPH yields improvements in control similar to those achieved with 2 daily injections [92].

Cost Considerations

Treating T2DM imposes a great financial burden on individuals living with diabetes and their families due to the high cost of the medications. Table 4 and Table 5 provide information on the cost of non-insulin and insulin diabetes medications for patients who do not have prescription insurance coverage. From a practical standpoint, choice of diabetes agents is largely influenced by insurance formularies.

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