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What do the guidelines say about use of biosimilar insulin therapy? Simple practical considerations to guide clinicians in different patient subgroups—Sharing Canadian perspectives

Abstract
Background
The rising cost of insulins are significantly impacting health care expenditure, thereby limiting access to treatment for more people affected by diabetes. Fear and misunderstanding of insulin therapy have worsened with the emergence of biosimilar insulins. Biosimilars are not the same as generic medications. Generic medication contains identical ingredients to the reference, whereas biosimilar medication is highly comparable but not necessarily identical to the reference.
Results
There are five biosimilar insulins currently available in Canada: insulin glargine (U-100) as the biosimilar insulins, Basaglar® and Semglee®, insulin lispro (U-100) as the biosimilar insulin, Admelog® and insulin aspart (U-100) as the biosimilar insulins, Trurapi® and Kirsty ™. Recent clinical trials have demonstrated comparable efficacy, safety and immunogenicity for biosimilar insulins compared with reference insulins. The dosing of biosimilar insulins is also the same as the reference for initiating, switching (1:1) and titrating. Regulatory agencies, payors and clinical practice guideline committees are initiating biosimilar initiatives aimed at reducing costs, impacting more patients worldwide. While few studies have evaluated biosimilar insulin use in a real-world clinical practice setting, the descriptive patterns retrieved from the LMC Diabetes Registry reflect the Ontario Ministry of Health’s changes in biologic drug policy that were implemented to promote the use of biosimilar insulins.
Conclusion
Many health care providers are largely unfamiliar with biosimilar insulins. This limits the acceptance of biosimilar insulins by patients, as it is related to the comfort of health care providers in educating patients. Tailoring effective conversations to patient needs ensures the best possible therapeutic outcomes.
Plain Language Summary
This review article intends to review the efficacy and safety data from pivotal clinical trials with biosimilar insulins, as well as the regulatory and health economic considerations which underpin the safe and cost-effective use of biosimilar insulin therapy. Biosimilars are not the same as generic medications. Generic medication contains identical ingredients to the reference, whereas biosimilar medication is highly comparable but not necessarily identical to the reference. There are five biosimilar insulins currently available in Canada: insulin glargine (U-100) as the biosimilar insulins, Basaglar® and Semglee®, insulin lispro (U-100) as the biosimilar insulin, Admelog® and insulin aspart (U-100) as the biosimilar insulins, Trurapi® and Kirsty™. Data for biosimilars must be submitted in a stepwise approach to demonstrate similarity to the reference biologic under the following categories: structure & function, human clinical trials, comparative studies evaluating efficacy and safety and manufacturing quality control. Recent clinical trials have demonstrated comparable efficacy, safety and immunogenicity for biosimilar insulins compared with reference insulins. The dosing of biosimilar insulins is also the same as the reference for initiating, switching (1:1) and titrating. Health care providers are encouraged to stay up to date on the latest guidelines and recommendations regarding biosimilar insulin interchangeability to ensure safe and cost-effective use of these products. Regulatory agencies, payors and clinical practice guideline committees are initiating biosimilar initiatives aimed at reducing costs, impacting more patients worldwide. While few studies have evaluated biosimilar insulin use in a real-world clinical practice setting, the descriptive patterns retrieved from the LMC Diabetes Registry reflect the Ontario Ministry of Health’s changes in biologic drug policy that were implemented to promote the use of biosimilar insulins. A summary of adults with diabetes from this registry showed 3.8% of individuals with T1D were prescribed Basaglar® before April 2023 compared to 12.0% after January 2024. For the T2D cohort, the use of basal biosimilar insulins, Basaglar® and Semglee®, similarly increased by approximately 10% and 2% after January 2024, respectively. The use of bolus biosimilar insulins also increased after January 2024 by approximately 28% in the T1D cohort and 60% in the T2D cohort using insulin therapy. Many health care providers are largely unfamiliar with biosimilar insulins. This limits the acceptance of biosimilar insulins by patients, as it is related to the comfort of health care providers in educating patients. People living with diabetes must have access to safe and effective treatment options, and they should be able to obtain appropriate medications at an affordable price and in a fair and timely manner.

Machine learning approach on plasma proteomics identifies signatures associated with obesity in the KORA FF4 cohort

Abstract
Aims
This study investigated the role of plasma proteins in obesity to identify predictive biomarkers and explore underlying biological mechanisms.
Methods
In the Cooperative Health Research in the Region of Augsburg (KORA) FF4 study, 809 proteins were measured in 2045 individuals (564 obese and 1481 non-obese). Multivariate logistic regression adjusted for confounders (basic and full models) was used to identify obesity-associated proteins. Priority-Lasso was applied for feature selection, followed by machine learning models (support vector machine [SVM], random forest [RF], k-nearest neighbour [KNN] and adaptive boosting [Adaboost]) for prediction. Correlation and enrichment analyses were performed to elucidate relationships between protein biomarkers, obesity risk factors and perturbed pathways. Mendelian randomisation (MR) assessed causal links between proteins and obesity.
Results
A total of 16 proteins were identified as significantly associated with obesity through multivariable logistic regression in the basic model and subsequent Priority-Lasso analysis. Enrichment analyses highlighted immune response, lipid metabolism and inflammation regulation were linked to obesity. Machine learning models demonstrated robust predictive performance with area under the curves (AUC) of 0.820 (SVM), 0.805 (RF), 0.791 (KNN) and 0.819 (Adaboost). All 16 proteins correlated with obesity-related risk factors such as blood pressure and lipid levels. MR analysis identified AFM, CRP and CFH as causal and potentially modifiable proteins.
Conclusions
The protein signatures identified in our study showed promising predictive potential for obesity. These findings warrant further investigation to evaluate their clinical applicability, offering insights into obesity prevention and treatment strategies.

Targeting apolipoprotein C-III: a game changer for pancreatitis prevention in severe hypertriglyceridemia

Purpose of review

The aim of this review is to examine recent advancements in RNA-targeted therapies for the management of severe hypertriglyceridemia (sHTG) and prevention of sHTG-associated acute pancreatitis.

Recent findings

Recent developments in RNA-targeted therapies, aimed at inhibiting apolipoprotein C-III (apoC-III), have demonstrated substantial and sustained reductions in triglyceride levels. Novel therapies, including antisense oligonucleotides (ASOs) and small interfering RNA (siRNA), such as volanesorsen, olezarsen, and plozasiran, have shown promising results in recent trials. These therapies not only effectively lower plasma triglyceride levels but also significantly reduce the incidence of acute pancreatitis.

Summary

SHTG is a high-burden metabolic disorder that is associated with a significantly increased incidence and severity of acute pancreatitis. Traditional lifestyle interventions and conventional therapies, including fibrates and n-3 fatty acids, often provide only modest reductions in triglycerides and fail to prevent sHTG-associated acute pancreatitis. The emergence of novel and targeted RNA-therapies represents a potential breakthrough in the management of sHTG and acute pancreatitis prevention.

Estimating healthcare resource utilisation and cardiovascular events in people with high body mass index and established cardiovascular disease

Abstract
Aims
Obesity and its complications contribute to the burden of cardiovascular disease (CVD). Here, we characterised individuals with high body mass index (BMI) and established CVD by assessing healthcare resource utilisation (HCRU) and costs, incidence of cardiovascular (CV) events and mortality.
Materials and Methods
This was a retrospective open cohort study using UK Discover data (study period: January 2004 to December 2019). Included were individuals aged ≥45 years with BMI ≥ 27 kg/m2, without type 1 or type 2 diabetes, and with established CVD (previous myocardial infarction, stroke or peripheral artery disease). Serial annual cross sections were assembled to generate prevalence and incidence cohorts and for mapping of HCRU, costs and the incidence of selected events. CVD and mortality trajectories were modelled using a Markov model. HCRU and costs were layered onto this model to obtain associated trajectories.
Results
In 2019, annual per-person healthcare costs for individuals with high BMI and established CVD (n = 27 313) were £3364. During 2015–2019, the incidence of major adverse CV events was 2812 per 100,000 person-years; the incidences of all-cause and CV mortality were 2896 and 774 per 100,000 person-years, respectively. Over 2022–2031, this population is projected to accrue estimated healthcare costs of £40.8 million. HCRU trajectory drivers included a history of CV events, older age, and multimorbidity.
Conclusions
Owing to a high disease and treatment burden, people with a history of CVD living with high BMI incur substantial healthcare costs and are at risk of mortality.

More Data Assuage Suicide Concerns With GLP-1 Agents

(MedPage Today) — Risk of suicidality wasn’t higher for type 2 diabetes patients starting on GLP-1 receptor agonists than for those on two other popular classes of diabetes drugs, a U.K. cohort study found.
In fully adjusted models, new initiators…

Are Compounded GLP-1 Drugs Safe?

This Medical News article discusses safety concerns around compounded semaglutide and tirzepatide, including how clinicians can help prevent dosing errors.

Study finds GLP-1 receptor agonists target fat over muscle for weight loss

Diabetes and obesity have become pressing health issues worldwide. Glucagon-like peptide-1 (GLP-1) receptor agonists, a class of medications widely used in the treatment of type 2 diabetes (T2D), have shown significant effectiveness in both lowering blood sugar levels and aiding weight loss due to their unique pharmacological mechanisms.