PMID- 34605142
OWN - NLM
STAT- MEDLINE
DCOM- 20220331
LR  - 20220722
IS  - 1463-1326 (Electronic)
IS  - 1462-8902 (Print)
IS  - 1462-8902 (Linking)
VI  - 24
IP  - 2
DP  - 2022 Feb
TI  - Ultra-rapid lispro shows faster pharmacokinetics and reduces postprandial glucose 
      excursions versus Humalog(R) in patients with type 2 diabetes mellitus in a 
      randomized, controlled crossover meal test early phase study.
PG  - 187-195
LID - 10.1111/dom.14561 [doi]
AB  - AIMS: To compare the pharmacokinetics (PK), glucodynamics (GD) and tolerability 
      following single and multiple daily subcutaneous doses of ultra rapid lispro 
      (URLi) and Humalog(R) in patients with type 2 diabetes mellitus (T2D). MATERIALS 
      AND METHODS: This was a two-part, randomized, double-blind Phase 1b study. Part A 
      used a six-period crossover design to assess PK and GD response to a solid mixed 
      meal tolerance test (MMTT) following a single dose of URLi or Humalog 
      administered 15 minutes before, immediately before, or 15 minutes after the start 
      of the meal. Part B evaluated URLi or Humalog during 2 weeks of multiple daily 
      dosing with a parallel design. The PK and GD were assessed following MMTTs at the 
      beginning and end of the 2 weeks when insulins were administered immediately 
      before the start of the meal. RESULTS: URLi increased the insulin exposure within 
      the first 30 minutes postdose by 2.2-fold and reduced the time to the early 
      half-maximal drug concentration by 22.6% compared with Humalog. Overall, URLi 
      resulted in better postprandial glucose lowering when dosed before, immediately 
      before, or after a meal. In comparing the same meal-to-dose timing between the 
      insulins, the postprandial glucose excursion over 5 hours was significantly 
      reduced by 29%-105% for all three dose timings (-15, 0 and +15 minutes) with 
      URLi. The PK and GD were sustained after daily subcutaneous dosing for 2 weeks in 
      patients with T2D. URLi had more hypoglycaemic events during the MMTTs; few 
      events occurred for both treatments during the 2 weeks of outpatient dosing. 
      CONCLUSIONS: URLi demonstrated accelerated insulin lispro absorption and greater 
      postprandial glucose reduction at different meal-to-dose timings compared with 
      Humalog and was well tolerated in patients with T2D.
CI  - (c) 2021 Eli Lilly and Company. Diabetes, Obesity and Metabolism published by John 
      Wiley & Sons Ltd.
FAU - Leohr, Jennifer
AU  - Leohr J
AUID- ORCID: 0000-0001-5434-7905
AD  - Eli Lilly and Company, Indianapolis, Indiana, USA.
FAU - Kazda, Christof
AU  - Kazda C
AUID- ORCID: 0000-0002-2538-2573
AD  - Eli Lilly and Company, Indianapolis, Indiana, USA.
FAU - Liu, Rong
AU  - Liu R
AD  - Eli Lilly and Company, Indianapolis, Indiana, USA.
FAU - Reddy, Shobha
AU  - Reddy S
AD  - Eli Lilly and Company, Indianapolis, Indiana, USA.
FAU - Dellva, Mary Anne
AU  - Dellva MA
AD  - Eli Lilly and Company, Indianapolis, Indiana, USA.
FAU - Matzopoulos, Mark
AU  - Matzopoulos M
AD  - Eli Lilly and Company, Indianapolis, Indiana, USA.
FAU - Loh, Mei Teng
AU  - Loh MT
AD  - Eli Lilly and Company, Indianapolis, Indiana, USA.
FAU - Hardy, Thomas
AU  - Hardy T
AD  - Vertex Pharmaceuticals, Boston, USA.
FAU - Klein, Oliver
AU  - Klein O
AD  - Profil, Neuss, Germany.
FAU - Kapitza, Christoph
AU  - Kapitza C
AUID- ORCID: 0000-0002-9700-2373
AD  - Profil, Neuss, Germany.
LA  - eng
SI  - ClinicalTrials.gov/NCT02703337
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20211027
PL  - England
TA  - Diabetes Obes Metab
JT  - Diabetes, obesity & metabolism
JID - 100883645
RN  - 0 (Blood Glucose)
RN  - 0 (Hypoglycemic Agents)
RN  - 0 (Insulin)
RN  - 0 (Insulin Lispro)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - Blood Glucose
MH  - Cross-Over Studies
MH  - *Diabetes Mellitus, Type 1/drug therapy
MH  - *Diabetes Mellitus, Type 2/chemically induced/drug therapy
MH  - Glucose/therapeutic use
MH  - Humans
MH  - Hypoglycemic Agents/adverse effects
MH  - Insulin/therapeutic use
MH  - Insulin Lispro
MH  - Postprandial Period
PMC - PMC9297897
OTO - NOTNLM
OT  - insulin therapy
OT  - pharmacodynamics
OT  - pharmacokinetics
OT  - type 2 diabetes mellitus
OT  - ultra-rapid insulin
COIS- OK is an employee of Profil. CK is an employee and co-owner of Profil, which has 
      received research funds from Eli Lilly, and has received research funds from 
      Adocia, Boehringer Ingelheim, Dance Pharmaceuticals, Eli Lilly, Johnson&Johnson, 
      Medimmune, MSD, Mylan, Nordic Bioscience, Novo Nordisk, Poxel, Roche Diagnostics, 
      Saniona, Sanofi, Senseonics, Zealand Pharma. All other authors are employees (CK, 
      JL, RL, SR, MAD, MM, MTL) or retired employees (TH and MPK) and serve as authors 
      for, Eli Lilly and Company and hold stock/shares in Eli Lilly and Company.
EDAT- 2021/10/05 06:00
MHDA- 2022/04/01 06:00
PMCR- 2022/07/20
CRDT- 2021/10/04 06:32
PHST- 2021/09/17 00:00 [revised]
PHST- 2021/06/14 00:00 [received]
PHST- 2021/09/28 00:00 [accepted]
PHST- 2021/10/05 06:00 [pubmed]
PHST- 2022/04/01 06:00 [medline]
PHST- 2021/10/04 06:32 [entrez]
PHST- 2022/07/20 00:00 [pmc-release]
AID - DOM14561 [pii]
AID - 10.1111/dom.14561 [doi]
PST - ppublish
SO  - Diabetes Obes Metab. 2022 Feb;24(2):187-195. doi: 10.1111/dom.14561. Epub 2021 
      Oct 27.