U-500 Insulin as a Component of Basal Bolus Insulin Therapy in Type 2 Diabetes

Abstract

Background: Changes in hemoglobin A1c (A1C), weight, and total daily insulin dose (TDD) were investigated following initiation of insulin U-500 (U500) alone or as part of a basal/bolus insulin (BBI) regimen. Subjects and Methods: Records of patients with type 2 diabetes who were prescribed U500 were retrospectively reviewed. Logistic regression analysis was used to investigate relationships between changes in A1C and use of U500 alone or as BBI. Results: Twelve patients were identified as using U500 alone (n = 2) or in combination with long-acting (LAI) (n = 7) or rapidacting (RAI) (n = 3) insulin. Reductions in A1C (9.5% at baseline vs. 7.7% at 6-9 months, P < 0.0001) and increases in weight (128.8 -32.7 vs. 131.5 -31.3 kg, P < 0.014) and TDD (260 -111 to 333 -106 units/day, P < 0.0002) were observed. Concurrent use of LAI or RAI with U500 did not predict improvements in A1C. Conclusions: U500 resulted in improvements in A1C and weight gain and increased TDD when used alone or as part of combination insulin therapy. Further investigations to define the optimal use of U500 are recommended.

The use of U‐500 regular insulin in the management of patients with obesity and insulin resistance

“…Amongst those using U-500 insulin alongside long acting U-100 insulin, HbA1c fell from a mean of 83 mmol/mol (9.7%) to 63 mmol/mol (7.9%) at 6-9 months follow-up. Similar results were reported in those using U-500 in combination with rapid acting U-100 insulin [baseline 78 mmol/mol (9.3%), follow-up 56 mmol/mol (7.3%)] [37].…”

Initiation of human regular U-500 insulin use is associated with improved glycemic control: a real-world US cohort study

“…Although this number is smaller than the number of propensity-matched pairs from the two previous real-world studies (684 9 and 1039, 10 respectively), it is close to the total number of U-500R-treated patients reported in the world's literature of published case series (N=524; most retrospective; combining MDI series 4 6 7 18 with off-label CSII use 4 6 7 19 20 and use in pregnancy 21 ). The overall HbA1c reduction of 0.68% in this cohort is statistically and clinically significant, but is less than that reported in the clinical case series (1.0–3.5% 4 6 7 18–20 ) and from the single RCT (1.0–1.7%). 15 However, this is not surprising since the prior clinical reports were conducted by investigators/institutions with particular clinical experience with use and titration of U-500R over time, thus likely representing more expert use than that captured by the Humedica EHR database for all U-500R use during the study period, within the prespecified study parameters.…”

“…Although U-500R therapy with concomitant use of basal or prandial U-100 insulin has been advocated for by some, 3 18 24 most case series have reported use of U-500R by itself 2 4–6 consistent with reported PK/PD prandial and basal characteristics of U-500R. 13 The two RCTs of U-500R also had algorithms using U-500R as insulin monotherapy.…”

“…The glycemic efficacy in our cohort, although novel, does not help to provide understanding of the higher incidence of hypoglycemia (setting not specified) observed in the propensity-matched U-500R versus U-100 insulin cohorts of the recent naturalistic studies 9 10 since we were not able to assess a matched cohort treated only with U-100 insulins in this database. Severe hypoglycemia has occasionally been reported in clinical case series 11 19 21 24 with no reports in others 18 27–29 and no severe hypoglycemia in the recent U-500R RCT. 15 One case series (N=53) reported eight episodes of severe hypoglycemia occurring in six patients.…”

Development and Implementation of a U-500 Regular Insulin Program in a Federally Qualified Health Center

“…Based on a meta-analysis (9), severe hypoglycemia was not reported to be a problem and occurred at similar rates to U-100 regular insulin. However, Dailey and Tannock (5) noted that mild hypoglycemia increased slightly during the first few months, but then typically declined thereafter.…”