Profil's scientific publications in 2023 - an overview

Posted by Dr. Sabine Arnolds on Sep 26, 2023 9:27:00 AM
This is a short overview of key features and results of clinical trials performed at Profil and papers with Profil authorship that were published between January and August 2023. 
The clinical trial publications in the given period are related to the following topics:
Novel insulins / Biosimilar insulins
  • Pharmacokinetics (PK)/Pharmacodynamics (PD) of the novel basal insulin FC (insulin efsitora alfa), an insulin fusion protein [1],
  • PK/PD of once-weekly basal Insulin Icodec after subcutaneous (s.c.) administration in the thigh, abdomen or upper arm in people with type 2 diabetes [2],
  • ADO09, a co-formulation of pramlintide and insulin A21G [3],
  • PK/PD equivalence trial on Biocon’s biosimilar Insulin N versus Humulin N [4],
  • PK/PD of insulin lispro + meloxicam versus insulin lispro PK/PD over 10 days [5],
  • Tirzepatide versus semaglutide – effects on appetite, energy intake and fat mass in people with type 2 diabetes [6]   
Other compounds 
  • BI 187004, an inhibitor of 11 beta-hydroxysteroid dehydrogenase-1 [7]
  • Noninvasive Continuous Glucose Monitoring (CGM) with a novel wearable dial resonating sensor [8].
In addition, the following articles with Profil‘s (co)authorship were published during the first eight months of 2023: 
  • An integrated safety and efficacy analysis of dasiglucagon in type 1 diabetes [9],
  • Phase 1 studies of the safety and PK/PD of the dual glucagon receptor/GLP-1 receptor agonist BI 456906 [10], and 
  • A commentary on oral insulin [11].



Key features and results of Profil publications on novel insulins and biosimilar insulins Jan – Aug 2023:


1. Once-weekly novel basal insulin Fc (insulin efsitora alfa) [1]:

These were the First-In-Human clinical trials of insulin efsitora alfa investigating its safety, tolerability, PK and glucose PD. The single ascending dose (SAD) study over 15 days assessed four different doses (5-35 mg) in 16 healthy trial participants and 57 people with type 2 diabetes (T2D). In the 6-week multiple ascending dose (MAD) trial 33 people with T2D previously treated with basal insulin either received once daily insulin glargine or a one-time loading dose of insulin efsitora alfa followed by once-weekly dosing (1-10 mg). 

Key results of insulin efsitora First-in Human SAD and MAD trial [1]


SAD trial


PK half-life of insulin efsitora alfa was approximately 17 days resulting in a sustained dose-dependent decrease in fasting blood glucose for 5 days or more. No severe hygoglycemia occurred.


MAD trial


Low peak-to-trough ratio of insulin efsitora alfa of 1.14 after the last dose at week 6 (steady state). Over the 6-week period 7-point glucose profiles remained constant and similar to insulin glargine. Rates and duration of hypoglycemic events were also comparable to insulin glargine.



Insulin efsitora alfa was well tolerated and exhibited a PK/PD profile suitable for once-weekly dosing.




2. Once-weekly basal insulin Icodec [2]:

This randomized, open-label, crossover trial investigated the PK and PD characteristics of once weekly basal insulin icodec after single subcutaneous (s.c.) injections (5.6 U/kg) in the thigh, abdomen or upper arm in 25 individuals with type 2 diabetes. Frequent PK sampling was performed until 35 days post-dose. 

Key results of once-weekly basal insulin icodec administered as single dose to three different injection regions (abdomen, thigh, upper arm) [2]


Total icodec exposure (AUC0-∞,SD)


Was similar between injection in the abdomen, thigh and upper arm

Maximum icodec concentration (Cmax)


Was higher for abdomen (by 17%, p=0.002) and upper arm (by 24%, p<0.001) versus thigh. When simulated to steady state, smaller differences in Cmax were seen for abdomen (by 11%, p=0.004) and upper arm (by 16%, p<0.001) versus thigh


Geometric mean glucose- lowering effect 36-60 h post-dose


Was comparable for thigh, abdomen and upper arm


Icodec can be administered s.c. in the thigh, abdomen or upper arm with no clinically relevant difference in exposure and with a similar glucose-lowering effect.



3. ADO09, a co-formulation of pramlintide and insulin A21G [3]

This randomised, double-blind, two-period crossover trial compared prandial administration of ADO09 or insulin aspart over 24 days in trial participants with type 1 diabetes in a low-dose (LD) group (n=28; ≤40 U bolus insulin per day) versus a high-dose (HD) group (n=16, 40-75 U bolus insulin per day). Glucodynamics through continuous glucose monitoring (CGM) as well as PK/PD profiles following mixed-meal tolerance tests (MMTT) were evaluated at baseline and end of treatment.

Key results of the ADO09 versus insulin aspart trial in T1D [3]


Glucose increments from 0 to 4 h following MMTT


Were 39% (not statistically significantly) lower with ADO09 in the low-dose group and 69% lower in the high-dose group.

Mean CGM glucose during ambulatory treatment


Was lower with ADO09 than with insulin aspart (LD: -8.2 ± 7.9 mg/dl; HD: -7.0 ± 10 mg/dl)



Time in range (70-180 mg/dl)


Improved in both LD and HD group by +4%


Body weight (kg)


Declined significantly with ADO09 (LD: -0.8 kg; HD: -1.6 kg)

Hypoglycemic events




Were more frequent with ADO09 versus insulin aspart (LD: 142 vs 115 events; HD: 96 vs 79)


Gastrointestinal events occurred more frequently with ADO09, but were generally transient, and no other safety signals were identified



Compared to insulin aspart, ADO09 was well tolerated and effective in a wide range of dosage, significantly improving the average BG level and body weight during 24 days of ambulatory treatment. Meal test profiles confirmed these improvements of glycemic patterns and other responses with ADO09.



4. Biocon’s biosimilar Insulin N [4]

The aim of this trial was to establish PK and PD equivalence of Biocon’s biosimilar insulin N with US-licensed Humulin® N in 90 healthy subjects (85 completers). The design was a single-centre, randomised, double-blind, three-period, six-sequence, partially replicated, 24-hour euglycemic clamp study.

Key results of Biocon’s biosimilar insulin N PK/PD equivalence euglycemic clamp trial vs Humulin N [4]


Primary PK endpoints:
AUC INS.0-24h,
C INS.max


Equivalence established.


Primary PD endpoints:
AUC GIR0-24h,


Equivalence established.


PK and PD equivalence was shown between Biocon’s biosimilar insulin N and Humulin® N in healthy subjects and both treatments were well tolerated and considered safe.


5. Insulin lispro + meloxicam [5]

This phase 1 clinical trial evaluated the effect of meloxicam on insulin lispro PK and glucose PD over 10 days of continuous subcutaneous insulin infusion (CSII) at one infusion site in trial participants with type 1 diabetes. The study design was double-blind, two-way crossover. 20 participants randomly received U100 insulin lispro and U100 Insulin lispro + 0.25 mg/mL meloxicam (LY900027).

Key results of Insulin lispro PK and PD + meloxicam [5]



AUC Ins0-5h after bolus administration prior to a MMTT


Was significantly lower on Day 10 versus Day 3 for LY900027 (-19%) and insulin lispro (-14%); the AUC INS0-5h did not differ significantly between treatments.

C INS.max


Increased with LY900027 and insulin lispro (by ~14%-23% and ~16%-51%) on days 5, 7 and 10 vs Day 3. The C INS.max of LY900027 was ~14-23% lower than that of insulin lispro on Days 7 and 10.

Accelerated insulin absorption and a modest loss of insulin exposure resulted in a loss of MMTT glycemic control at later time points.



The PK of insulin changed over catheter wear time even when an anti-inflammatory agent was present. Postprandial glycemic control was adversely affected by the accelerated insulin absorption and decreased insulin exposure.



For further information regarding the remaining clinical trial publications listed above, please also refer to our website.


Topics: Clinical Trials in Diabetes, Clinical Trial Methods