Combination Injectable Therapy

The new guidelines have significantly updated the original approach to the use of insulin in patients whose glucose control remains poor, despite the use of three antihyperglycemic drugs. The 2012 position statement “endorsed the addition of one to three injections of a rapid-acting insulin analogue dosed before meals” or, in selected patients, simpler premixed formulations of intermediate- and short/rapid acting insulins in fixed ratios.The updated guidelines, based on data that emerged since 2012,16,17 recommend that either a GLP-1 RA or prandial insulin could be used in this setting, “with the former arguably safer, at least for short-term outcomes.”12,16,18,19 While combining basal insulin with other oral agents in those with uncontrolled diabetes is a viable option, adding a GLP-1 RA might be an “attractive option” in obese individuals because of the positive impact that this medication class has on weight loss. It might also be a viable option for patients who “may not have the capacity to handle the complexities of a multi-dose insulin regimen.”2

In patients who do not respond adequately to the combination of basal insulin and a GLP-1 RA, mealtime insulin in a combined “basal-bolus” strategy should be used instead.2,20 Adding an SGLT2 inhibitor at this stage may further improve control and reduce the amount of insulin required—especially in obese, highly insulin-resistant patients requiring large doses of insulin.2,21 A TZD may also reduce HbA1c and have an insulin-sparing effect, but may cause weight gain, fluid retention, and risk of heart failure. Concentrated insulins (eg, U-500 Regular) may minimize injection volume, but must be carefully prescribed with “meticulous communication with both patient and pharmacist” regarding proper dosing instructions.2