Diagnosis: Type 1 Diabetes Mellitus.
Treatment: Humalog Kwikpen (insulin lispro (human)).

The insurer denied Humalog Kwikpen (insulin lispro (human)). The denial was overturned.

This is a male patient with Type 1 diabetes mellitus. He weighs 114 kg, and he uses > 100 unit/dose in his pump. He had used U100 Novolog, but he was forgetting doses, as his pump only administers 25 units/bolus. He was switched to using U200, allowing his pump reservoir to last several days and allowing him to take his full doses at meals, since the insulin is more concentrated. The request is for Humalog U200.

The formulary drugs would be likely to cause the patient an adverse reaction, due to the fact he was not maintaining adequate glucose control and was forgetting the doses required at mealtime. Once the insulin was switched to Humalog for a higher concentration, he was not forgetting the mealtime doses and was obtaining better glucose control. Type 1 diabetes leads to significant co-morbidities if not controlled adequately.

The request for Humalog U200 will be and is more effective than the formulary drug, since he will be able to take the whole dose/bolus at once and, hence, not forget/miss part of it, as with the formulary drugs this more concentrated dose is not available.

"No significant variation in fasting blood glucose, HbA1c, severe or mild hypoglycemic rate and daily fast-acting insulin analog dose was observed with U-100 lispro while U-200 lispro treatment was associated with a significant improvement of all the above mentioned parameters and with around 20% decrease in insulin requirement. Moreover patients' answers to the questionnaire pointed out a higher preference for U-200 lispro for continuing treatment due to fewer difficulties completing injection." (Gentile, et al. 2018).

"Insulin injection volume is particularly important in patients using higher insulin doses. In a meta-analysis of 5 phase 3a clinical trials, approximately 35% of subjects with Type 2 diabetes mellitus treated with basal insulin required>60 units daily [9]. In addition, people with severe insulin resistance may need to inject>100 units or 1mL of Reg-U100 insulin at a time [10]. When switching these people from U-100 insulin regimens to U-500 insulin, the reduced volume of dosing with the U-500 concentration allowed treatment of people with severely insulin-resistant diabetes with 2 to 3 injections daily compared to up to 10 injections a day with U-100 insulins [11, 12]. Reg-U500 and the newer concentrated insulin preparations now available (Table 1), may provide potential advantages including decreased number of injections, decreased pain, less frequent pen changes, ability to deliver larger doses, improved pen mechanics, and enhancements of continuous subcutaneous insulin infusion." (Schloot, et al. 2019).

"Three higher concentration insulin products (insulin lispro 200 units/mL, insulin degludec 200 units/mL, and insulin glargine 300 units/mL) received US Food and Drug Administration (FDA) approval in 2015. Although human regular insulin 500 units/mL (U-500) was approved in 1997, a pen and dedicated U-500 syringe became available in 2016. These products offer more treatment options for the increasing numbers of patients requiring insulin to achieve and maintain glycemic targets. Higher concentration insulins have some unique safety and efficacy considerations. Important considerations when transitioning patients from the 100 unit/mL concentration (U-100) to the higher concentration include bioequivalence, pen dose increments, and pen appearance. Bioequivalent insulins have similar pharmacokinetic properties and no dose adjustments are expected when transitioning from the U-100 to the higher concentration." (Reid et al. 2017).

Based on the above, the insurer's denial of Formulary Exception for Humalog Kwikpen (insulin lispro (human)) is overturned.