Building Competency in Diabetes Education THE ESSENTIALS

TREATMENT MODALITIES: PHARMACOLOGICAL THERAPIES | 6-

Combination therapy: Basal insulin and non-insulin antihyperglycemic agents Insulin therapy should be initiated if glycemic targets are not attained with lifestyle modification and the use of two or more oral antihyperglycemic agents. Insulin is the most potent antihyperglycemic agent and has no maximum dose. The combination of insulin with other antihyperglycemic agents has been shown to decrease A1C levels by 0.9 -1.2% (24). When starting insulin therapy, a single dose of basal insulin is preferred. The combination of basal insulin with antihyperglycemic agents results in better glycemic control, reduced insulin requirements, less weight gain and hypoglycemia versus insulin alone (24). The 4-T study demonstrated treatment with basal, prandial or biphasic insulin therapies resulted in similar reductions in A1C and FBG with less hypoglycemia and weight gain in the basal insulin therapy group (123). Another study revealed participant-reported treatment satisfaction was higher with basal analogue therapy compared to oral agents, NPH, and premixed insulin (123). While bedtime basal insulin is used to suppress nocturnal hepatic glucose production and target FBG levels, non-basal insulin antihyperglycemic agents help to control daytime BG levels with some AHAs (GLP-1 RA and sulfonylureas) also having an effect on FBG levels. Studies have shown that 30% to 50% of people with type 2 diabetes can achieve an A1C of ≤7.0% with basal alone (123). The combination of antihyperglycemic agents such as metformin, DPP-IV inhibitors, GLP1-RA and SGLT2 inhibitors provide the added glucose lowering benefit, with less hypoglycemia and may minimize the weight gain associated with insulin therapy (42). AHAs with demonstrated cardiorenal benefit when used in high-risk cardiorenal populations, should be used in the doses shown to confer cardiorenal benefit before basal insulin is uptitrated. A Cochrane review of 37 trials, involving 3,227 participants, compared insulin monotherapy with the addition of an oral antihyperglycemic agent in people with type 2 diabetes already treated with insulin therapy. The addition of oral agents to insulin reduced A1C by 0.4% to 1%, and total daily insulin dose. The combination of metformin with insulin resulted in 2.1 kg less weight gain compared with insulin monotherapy. In comparison, adding sulfonylureas to insulin was associated with a weight gain of 0.4 kg to 1.9 kg and higher rates of hypoglycemia (124).

For more information on managing diabetes with insulin, refer to “pharmacological management with insulin” later in this chapter.