Comparison of Glargine to Degludec Insulin Transition With or Without a Bridging Glargine Dose
Comparison of Glargine to Degludec Insulin Transition With or Without a Bridging Glargine Dose
This study evaluates direct switching vs use of a bridging dose from insulin glargine to
 insulin degludec in type 1 DM patients. Half of the participants will receive a bridging
 insulin glargine dose along with the 1st dose of degludec, while other half will receive a
 placebo and 1st dose of degludec.
Insulin degludec (IDeg), an ultra-long-acting basal insulin, is increasingly used to treat
 patients with type 1 diabetes (T1D). IDeg has a half-life of 25 hours and duration of action
 exceeding 42 hours in patients with T1D and as a result does not require as stringent a
 dosing schedule as other basal insulins. However, steady state concentration of IDeg is not
 reached until 2 to 3 doses are administered daily, and this may result in greater glycemic
 variability in the 24 to 72 hours following the initiation of therapy with IDeg.

 Our hypothesis is that among patients who transition from insulin glargine to IDeg, those who
 use a bridging dose of insulin glargine will not have a significant change, on average, in
 time spent in target glycemic range during the transition period, whereas, those
 transitioning directly to IDeg will have a significant change in this parameter. We further
 hypothesize that those using the bridging dose of insulin glargine will have less
 hypoglycemia, less hyperglycemia and need fewer correction boluses than the direct-conversion
 patients during the transition period.

 Though IDeg is being increasingly used in clinical practice, there are no guidelines on what
 is the best way to transition patients from other long-acting insulins, such as glargine, to
 IDeg. The package insert recommends 1:1 dose conversion from other basal insulins to IDeg,
 but this does not account for the time taken by IDeg to achieve steady state (typically 48-72
 hours). There is no guidance on what to do in those 48-72 hours. Given the time taken for
 IDeg to achieve steady state, the period of transition from one insulin to another, can
 result in significant glycemic variation in the 24-72 hours after the first dose. We want to
 study how best to avoid or minimize this and the option of using a small dose of their
 original long-acting insulin has anecdotal evidence of success in our practice.
Inclusion Criteria:

 -  Patients must meet ALL inclusion criteria to be included in the study.

 1. Patient age is 18-75 years.

 2. Diagnosis of T1D of at least 1-year duration.

 3. Has the ability to provide informed consent before any trial-related activities.

 4. Treated with insulin glargine as their basal insulin in the 3 months preceding
 screening visit.

 5. Stable insulin regimen (defined as change of <20% in the total daily dose of
 insulin and no change to the basal insulin agent) over the 3 months preceding the
 screening visit.

 6. Patient willing to dose their basal insulin at bedtime.

 7. Hemoglobin A1c < 9% in the 3 months preceding screening visit.

 8. Able to self-administer their insulin doses.

 9. Able to do self-monitoring of blood glucose using a glucose meter and willing to
 do this at least 2 times daily for patients using a CGM that requires calibration
 prior to the study and 4 times daily for patients who were not using a CGM prior
 to the study.

 10. Agreeable to the use of a continuous glucose monitor (CGM) for the duration
 required in the study. If already using a CGM prior to the study, then agreeable
 to wearing the blinded study CGM concurrently during the study period.

 11. Will be reachable by phone and/or email to comply with study procedures.

 12. Will be able to comply with study procedures, per investigator's opinion.

 13. Patient agrees to not use correctional insulin unless BG ≥250 for the 48 hours
 before and after 1st dose of IDeg.

 Exclusion Criteria:

 -  Patient must not have ANY of the exclusion criteria to be included in the study.

 1. Patients with eGFR <30 on at least 2 measurements within 1-year of the screening
 visit.

 2. History of myocardial infarction within 6 months preceding the screening visit.

 3. Patients taking non-insulin medications for the glycemic management of T1D
 (including metformin, DPP-4 inhibitors, GLP-1 receptor agonists, SGLT-2
 inhibitors, thiazolidinediones, alpha-glucosidase inhibitors, pramlintide)

 4. Known or suspected allergy to IDeg or one of its excipients.

 5. Pregnant, planning to become pregnant in the next 3 months or breastfeeding.

 6. Participation in a clinical trial with investigational drug within 1 month of the
 screening visit or at present.

 7. Skin condition that prevents the insertion of the CGM.

 8. Previously randomized and received drug in this study.

 9. Presence of decompensated or poorly controlled psychiatric conditions.

 10. Current known or suspected illicit substance use.

 11. Any anticipated surgery or procedure in the next 14 days.

 12. Patients using U-300 glargine as their basal insulin.

 13. Patients using insulin afrezza as their short-acting insulin.

 14. Use of glucocorticoid burst/pulse therapy within 14 days prior to screening visit
 (chronic stable glucocorticoid doses are acceptable).