This is a short overview of key features and results of clinical trials performed at Profil and papers with Profil authorship that were published in 2025.
We published on the following topics:
Novel insulins/biosimilar insulins
An open-label, multiple ascending dose trial of orally administered insulin Tregopil in patients with type 1 diabetes mellitus to evaluate its pharmacokinetics, pharmacodynamics, safety and tolerability [1]
Once-weekly insulins [2]
Biosimilar insulins: Narrative review of the regulatory framework and registration studies. [3]
Incretins
Consensus report on glucagon-like peptide-1 receptor agonsits as adjunctive treatment for individuals with type 1 diabetes using an automated insulin delivery systems. [4]
Greater improvement in insulin sensitivity per unit weight loss associated with tirzepatide versus semaglutide: An exploratory analysis. [5]
Devices
A prospective pilot study demonstrating noninvasive calibration-free glucose measurement. [6]
Treatment Satisfaction and Well-Being With Continuous Glucose Monitoring in People With Type 1 Diabetes: An Analysis Based on the GOLD Randomized Trial [7]
Methodology
Evaluating the adequacy of coefficient of variation and standard deviation as metrics of glucose variability in type 1 diabetes based on data from the GOLD and SILVER Trials. [8]
Key features and results of selected Profil publications in the metabolic space
Insulin Tregopil
In this phase one, open label, MAD trial, the safety, tolerability, pharmacokinetics and pharmacodynamics of oral insulin Tregopil were evaluated in 37 enrolled patients with type 1 diabetes.
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Key results of insulin Tregopil MAD trial [1] |
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Safety assessment |
Overall, the safety profile indicated no safety concern except a non-severe PD effect (hypoglycemica) which did not increase with increasing doses. |
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PK/PD parameters |
The variability of PK/PD parameters was high. Insulin Tregopil demonstrated rapid onset of action. Peak blood concentrations were reached within 15-20 minutes post-dosing. After dosing, the PD effect lasted for up to 105 minutes. |
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Conclusion |
Fixed-dose oral insulin Tregopil reduced the requirement for insulin aspart supplementation although it is no viable stand-alone option for the daily management of type 1 diabetes. Oral Tregopil could be explored with a flexible dosing approach and be titrated based on individual needs. |
Once-weekly insulins
In this narrative review, Dr. Tim Heise and Dr. Hans de Vries discuss the mechanisms of prolongation, early clinical research study results and the registration studies of once-weekly insulins insulin icodec and insulin efsitora alfa.
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Once-weekly insulins [2] |
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Focus & mechanism |
Icodec: prolongation via acylation (strong albumin binding) plus reduced insulin receptor affinity; unlike degludec, it does not form multihexamers subcutaneously Efisitora alfa: single-chain insulin coupled to an IgG2 Fc domain; prolongation mainly via FcRn recycling plus reduced insulin receptor affinity For both: reduced renal clearance is discussed and dose adjustment in renal impairment is not necessary |
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Evidence synthesis |
In type 2 diabetes, glycemic control is generally comparable to daily basal insulin. Icodec shows a small HbA1c advantage in several studies, while efsitora appears broadly similar to daily comparators offering more convenience to patients reducing the injection frequency by a factor of 7. In type 1 diabetes, HbA1c/TIR after once-weekly insulins are similar to daily insulins while increasing clinically significant or severe hypoglycemia. |
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Conclusion |
Once-weekly insulins mark a major innovation after insulin’s introduction. Their pharmacologic soundness and clinical efficacy are established, yet optimization of titration and education is needed for safer management of hypoglycemia and dose-timing awareness. |
Biosimilar insulins
In this review, Dr. Tim Heise and Dr. Hans de Vries provide an overview of pivotal phase 1 clamp and supportive larger phase 3 studies which supported registration of approved biosimilar insulins in EU and US.
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Biosimilar insulins [3] |
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Biosimilars: available but underused |
Despite EU availability since 2014 and multiple approvals in EU/US, uptake of biosimilar insulins has been limited, partly due to the perception they might be inferior. |
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Core evidence: analytics, preclinical and phase 1 glucose clamps |
Approval for biosimilars relies on comparative analytical and functional work, receptor and cell studies, and pivotal hyperinsulinaemic euglycaemic clamp studies to confirm matching time-action profiles. Large phase 3 trials are typically supportive rather than required. |
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Conclusion |
Approved biosimilars can be used confidently. EU and US regulatory approaches ensure no clinically meaningful differences compared to reference insulins. |
Did you know?
Profil performed clinical trials for all biosimilar insulins that are approved in the EU and US.
Insulin sensitivity associated with tirzepatide vs semaglutide
In this analysis, the relationship between weight loss and insulin sensitivity in response to tirzepatide or semaglutide was explored based on post hoc exploratory analysis of a 28-week, double-blind, randomized trial in people with type 2 diabetes treated with metformin, randomized to tirzepatide 15 mg, semaglutide 1 mg or placebo.
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Insulin sensitivity associated with tirzepatide vs semaglutide [5] |
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Insulin sensitivity |
Tirzepatide was associated with greater improvement than semaglutide in insulin sensitivity assessed using hyperinsulinemic euglycemic clamps. Changes in insulin sensitivity with tirzepatide were associated with change in weight. With semaglutide, the change in insulin sensitivity was less strongly correlated with change in weight. |
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Conclusion |
Improvement in insulin sensitivity was proportional to weight and fat loss, with greater strength of association with tirzepatide. Tirzepatide was associated with greater improvement in insulin sensitivity per unit weight loss than semaglutide. This association could not simply be described by greater weight or fat loss. |
Noninvasive calibration-free glucose measurement
In this blinded clinical trial, a novel spectroscopy-based system for measuring glucose noninvasively and without per-subject calibration was examined.
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Noninvasive calibration-free glucose measurement [6] |
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Subjects |
Twenty subjects were enrolled. Fifteen were used for the development set and five for the validation set. Participants were adults with insulin-treated diabetes and median HbA1c of 7.3% (IQR =6.7-7.7) |
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Computational model |
The computational model was based on machine learning mechanisms and resulted in mean absolute relative difference of 14.5% and 96.5% of the paired glucose data points in the A plus B zones of the Diabetes Technology Society error grid. Correlation between the average model sensitivity by wave length and spectrum of glucose was 0.45 (P<0.001). |
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Conclusion |
Raman spectroscopy coupled with advanced computational methods can enable continuous, noninvasive glucose measurement without per-subject invasive calibration. |
If you would like to learn more, you can access all clinical trial publications mentioned on our website.