4.6.0.0 Combination Injectable Therapy
If basal insulin has been titrated to an acceptable fasting blood glucose level (or if the dose is >0.5 units/kg/day) and A1C remains above target, consider advancing to combination injectable therapy (Fig. 9.2). Thisapproach can use a GLP- 1 receptor agonist added to basal insulin or multiple doses of insulin. The combination of basal insulin and GLP-1 receptor agonist has potent glucose-lowering actions and less weight gain and hypoglycemia compared with intensified insulin regimens (83-85). Two different once-daily fixed-dual combination products containing basal insulin plus a GLP-1 receptor agonist are available: insulin glargine plus lixisenatide and insulin degludec plus liraglutide.
Intensification of insulin treatment can be done by adding doses of prandial to basal insulin. Starting with a single prandial dose with the largest meal of the day is simple and effective, and it can be advanced to a regimen with multiple prandial doses if necessary (86). Alternatively, in a patient on basal insulin in whom additional prandial coverage is desired, the regimen can be converted to two or three doses of a premixed insulin. Each approach has advantages and disadvantages. For example, basal/prandial regimens offer greater flexibility for patients who eat on irregular schedules. On the other hand, two doses of premixed insulin is a simple, convenient means of spreading insulin across the day. Moreover, human insulins, separately or as premixed NPH/Regular (70/30) formulations, are less costly alternatives to insulin analogs. Figure 9.2 outlines these options, as well as recommendations for further intensification, if needed, to achieve glycemic goals.
When initiating combination injectable therapy, metformin therapy should be maintained while sulfonylureas and DPP-4 inhibitors are typically discontinued. In patients with suboptimal blood glucose control, especially those requiring large insulin doses, adjunctive use of a thiazolidinedione or an SGLT2 inhibitor may help to improve control and reduce the amount of insulin needed, though potential side effects should be considered. Once a basal/bolus insulin regimen is initiated, dose titration is important, with adjustments made in both mealtime and basal insulins based on the blood glucose levels and an understanding of the pharmacodynamic profile of each formulation (pattern control). As people with type 2 diabetes get older, it may become necessary to simplify complex insulin regimens because of a decline in self-management ability (see Section 12 “Older Adults”).