Insulin Degludec Research Articles

De-intensification of basal-bolus therapy by replacing prandial insulin with once-weekly subcutaneous semaglutide in individuals with well-controlled type 2 diabetes: A single-centre, open-label randomised trial (TRANSITION-T2D).

The study aims to examine the outcome of replacement of prandial insulin with once-weekly subcutaneous semaglutide in people with type 2 diabetes reasonably controlled on multiple daily insulin injections (MDI). This single-centre, randomised, open-label trial enrolled a statistically predetermined sample of 60 adults with HbA1c ≤7.5% (58 mmol/mol) receiving MDI, with a total daily dose (TDD) ≤120 units/day. Participants were assigned 2:1 to subcutaneous semaglutide 1.0 mg plus insulin degludec, or to continue MDI. The primary outcome was percentage of subjects maintaining HbA1c ≤7.5% (58 mmol/mol) at Week 26. At Week 26, 90% of semaglutide and 75% of MDI subjects maintained HbA1c ≤7.5% (≤58 mmol/mol) (p = 0.18). Mean changes (95% CI) in HbA1c, weight and percentage body weight for semaglutide versus MDI, respectively, were -0.5% (-0.7, -0.3) versus 0.0% (-0.3, 0.3; p = 0.009); -8.9 kg (-9.9, -7.8) versus 1.5 kg (-0.1, 3.1; p < 0.001); and -8.6% (-9.6, -7.6) versus 1.4% (0.0, 2.8; p < 0.001). Insulin TDD decreased 56.0% (-62.3, -49.7) with semaglutide and increased 6.7% (-2.5, 16.0) with MDI (p < 0.001). Among semaglutide subjects, 58% reduced insulin TDD > 50%, 97.5% stopped prandial insulin and 45% lost >10% body weight. Participant treatment satisfaction scores trended higher with semaglutide. Hypoglycaemia frequency was similar between groups. In people with type 2 diabetes well controlled (HbA1c ≤7.5% [≤58 mmol/mol]) on MDI ≤120 units/day, replacing multiple daily injections of prandial insulin with once-weekly subcutaneous semaglutide can maintain and even improve HbA1c, lower body weight and lessen the burden of management.

Survey of fear and compliance of Insulin Degludec and Insulin Aspart injection in type 2 diabetes mellitus patients and analysis of influencing factors.

This study aims to investigate the fear and compliance of Insulin Degludec and Insulin Aspart (IDegAsp) injection in type 2 diabetes mellitus (T2DM) patients and study the factors influencing patient compliance. A total of 120 patients with T2DM treated from February 2019 to March 2022 were investigated and analyzed for fear and compliance on the Diabetes Fear of Injecting and Self-testing Questionnaire of diabetic patients and were divided into compliance and noncompliance groups according to the results to analyze the factors affecting patient compliance. The study found a high level of fear of IDegAsp injection among the 120 T2DM patients, with an average Diabetes Fear of Injecting and Self-testing Questionnaire score of (39.19 ± 4.59) points. Scores for medication compliance, dietary compliance, blood sugar monitoring, and lifestyle changes were (10.48 ± 1.52) points, (12.18 ± 2.27) points, (0.84 ± 0.12) points, and (9.13 ± 2.21) points, respectively. There was no significant difference between the compliance and noncompliance groups in terms of gender, age, lifestyle, educational level, occupation, current treatment method, family monthly income per capita, and medical payment method (P > .05). However, there were significant differences influenced by disease duration, complications, cognitive level, self-efficacy level, comorbidity count, and living status (P < .05). Multifactorial analysis showed that educational level, disease duration, complications, cognitive level, self-efficacy level, comorbidity count, and living status all affected patient compliance (P < .05). Educational level, disease duration, complications, cognitive level, self-efficacy level, comorbidity count, and living status are important factors affecting the fear and treatment compliance of IDegAsp injection in T2DM patients. These findings have implications for improving patient compliance and alleviating treatment fear.

Basal insulin analogues in type 1 diabetes – does one size fit all? Lessons from the HypoDeg trial based on single-patient outcomes

AimsIn the HypoDeg trial, a randomised crossover trial in people with type 1 diabetes prone to nocturnal severe hypoglycaemia, treatment with insulin degludec (IDeg) resulted in significantly reduced rates of nocturnal symptomatic hypoglycaemia and all-day severe hypoglycaemia compared to insulin glargine U100 (IGlar). We analysed HypoDeg data at a single-patient level to assess the proportion of participants to whom the overall result applied. MethodsPost hoc analysis using single-patient data (n=133) on nocturnal symptomatic hypoglycaemia, all-day severe hypoglycaemia and HbA1c. The outcome was classified as superior with IDeg, superior with IGlar, or similar between treatments for the three outcomes. We also assessed a composite endpoint based on these outcomes to evaluate the overall superior treatment for each participant. ResultsA higher percentage (38%) had IDeg as superior treatment compared to IGlar (15%) for nocturnal symptomatic hypoglycaemia (p < 0.001). There was no difference between the treatments for all-day severe hypoglycaemia or HbA1c. A higher percentage (44%) had a composite endpoint favouring IDeg compared to IGlar (16%) (p < 0.001). ConclusionsThe superiority of IDeg was confirmed in many of the participants. However, a minority had IGlar as superior treatment, underscoring the need for individualised basal insulin therapy in clinical practice.

Economic Evaluation of Once-Weekly Insulin Icodec from Italian NHS Perspective.

Icodec, once-weekly basal insulin, aims to simplify therapy management by reducing injection frequency for diabetic patients. The efficacy and safety of icodec were evaluated in the ONWARDS clinical development program. This study evaluates icodec economic and quality of life impact from the Italian National Healthcare System (NHS) perspective. A pharmacoeconomic study was developed to assess the once-weekly insulin icodec value, highlighting its potential to decrease needle use while improving adherence and quality of life. In the base case, a differential cost and cost-utility analysis over one year compared to once-daily insulin degludec were developed. Based on the comparison with degludec, a scenario analysis was planned between icodec and the mix of basal insulins available on the market. Economic evaluations included drug and administration costs, needles, and impact on adherence. The cost-utility analysis measured the utility associated with the weekly injection compared to the daily ones, resulting in an incremental cost-effectiveness ratio (ICER), measured as Δ€/ΔQALY (Quality Adjusted Life Years). To assess the robustness of the results, a deterministic one-way sensitivity analysis and a probabilistic sensitivity analysis were carried out. At an annual cost 25% higher than degludec, considering the economic benefits generated by the needle use reduction (-€51.10) and adherence improvement (-€54.85), once-weekly icodec grants no incremental cost and even potential savings per patient. Furthermore, icodec reported a utility advantage (0.023). It achieved a dominant incremental cost-effectiveness ratio (ICER) compared to degludec. The comparison with the mix of basal insulins also reported a cost-effectiveness profile. Sensitivity tests conducted confirmed the robustness of the findings, highlighting the key drivers of the analysis. Icodec represents a new therapeutic option to simplify basal insulin treatment. It also improves the patient's management and his quality of life, without increasing the economic burden for the Italian NHS, while guaranteeing an excellent cost-effectiveness profile.

Switching from Premixed Insulin to Insulin Degludec/Insulin Aspart for the Management of Type 2 Diabetes Mellitus: Implications of a Real-World Study on Insulin Degludec Dosing.

When switching from premixed insulin to insulin degludec/aspart (IDegAsp), IDegAsp usually starts at the same dose as the premixed insulin according to limited clinical experience or at a dose according to clinician discretion. The dose of insulin degludec used in the real world after switching has been poorly investigated. A retrospective analysis was conducted on patients with type 2 diabetes who switched from premixed insulin to IDegAsp from October 2016 to December 2023. Repeated measures analysis of variance was used to compare changes in insulin dose, glycated hemoglobin (HbA1c), fasting blood glucose (FBG), and postprandial blood glucose (PBG) before and after switching. Sixty-six patients with prior low-ratio premixed insulin and 22 with prior mid-ratio premixed insulin were included. Among the low-ratio insulin users, the total daily dose of insulin degludec (IDeg) decreased by 21.43% and 19.05% at 3 and 6months, respectively, after switching, compared with prior basal insulin dose (both p < 0.001). Conversely, among mid-ratio insulin users, the IDeg daily dose increased by 10.71% and 32.14% at 3 and 6months, respectively, after switching, compared with prior basal insulin dose (both p < 0.001). In all patients, HbA1c levels decreased by 0.70%, FBG decreased by 1.00mmol/l, and PBG decreased by 1.61mmol/l after 6months of switching (all p < 0.05); the total daily insulin dose and injection frequency significantly decreased after switching (both p < 0.05); age and disease duration did not affect IDegAsp effects on HbA1c reduction. In the setting of transition to IDegAsp from premixed insulin, the dose of basal insulin in the premixed formulation can be a valuable reference for adjusting insulin degludec dose. IDegAsp is superior to premixed insulin in blood glucose control with reduced total daily dose and injection frequency. IDegAsp could be the best choice for the management of diabetes in elderly patients.

Study on bioequivalence and influence of obesity-related indicators on pharmacokinetics and pharmacodynamics for insulin degludec in healthy subjects

This study aimed to evaluate the bioequivalence between test and reference insulin degludec (IDeg) and the effects of body composition on pharmacokinetics and pharmacodynamics of IDeg in Chinese healthy volunteers. In this randomized, open-label, crossover trial, 30 healthy Chinese males were assigned to receive a single subcutaneous dose (0.4 IU/kg) of each formulation under 24-h euglycemic hyperinsulinaemic clamp. Body compositions were analysed prior to administration and blood samples were collected at specific times. The 90% of primary pharmacokinetic parameters and 95% of primary pharmacodynamic parameters confidence intervals for the ratio of the least-squares geometric means were all in the range of 80–125%. As the fat content level increases, Cmax, AUC0−12 and GIR-AUC0−24 decreased whereas AUC24−96 increased sequentially. Therefore, the equivalence was demonstrated between test and reference, and in healthy Chinese volunteers, higher levels of adiposity are associated with slower rates of insulin absorption and distribution and the poorer glucose-lowering effect.

Icodec: A Novel Once-Weekly Basal Insulin for Diabetes Management.

To evaluate the efficacy, safety, and clinical implications of insulin icodec, a novel once-weekly basal insulin for the treatment of type 1 diabetes (T1D) and type 2 diabetes (T2D), with an emphasis on its advantages and challenges in comparison with existing daily basal insulins. A literature search was performed using PubMed, Google Scholar, Embase, and ClinicalTrials.gov up to August 26, 2024, using the search terms icodec and ONWARDS trial. Studies involving patients living with T1D or T2D on once-weekly insulin icodec compared with once-daily insulins glargine U100, glargine U300, and degludec were considered for this review. Relevant English-language studies and those conducted in humans were considered. Insulin icodec offers reduced dosing frequency and potentially superior glycemic management with a safety profile comparable to existing basal insulins. Insulin icodec once-weekly dosing could significantly improve convenience and efficacy over daily basal insulins, representing a significant innovation in insulin therapy. Insulin icodec emerges as a promising option for diabetes management, potentially improving treatment adherence and quality of life.

6905 The Necessity For New Criteria To Evaluate Overbasalization In East Asian Patients With Type 2 Diabetes Using Basal Insulin

Abstract Disclosure: H. Jang: None. Background: Overbasalization, which refers to adjusting the dose of basal insulin beyond an appropriate dose, should be avoided when using basal insulin in patients with type 2 diabetes. It is recommended to evaluate overbasalization when the basal insulin dose exceeds 0.5 units/kg/day or when post-meal glucose levels are &amp;gt; 180 mg/dL. However, this is an expert opinion, and specific criteria for East Asians have not been presented. Methods: Patients with type 2 diabetes using basal insulin (insulin glargine U-100, insulin glargine U-300, insulin degludec, NPH) at Seoul National University Bundang hospital from December 2020 to November 2023, with fasting plasma glucose (FPG) levels between 80 mg/dL and 130 mg/dL, were retrospectively analyzed. Patients with CKD ≤ grade 3b (estimated glomerular filtration rate &amp;lt; 45 mL/min/1.73m2), those taking medications such as steroids that may affect blood glucose levels, and patients undergoing cancer treatment were excluded. Results: A total of 548 patients were analyzed. The mean age of the subjects was 64.7 ± 12.4 years, with 299 (54.6%) being male, and the mean body mass index was 25.1 ± 6.6 kg/m2. The mean duration of diabetes was 18.1 ± 9.6 years. The mean HbA1c level was 7.7 ± 1.1%, while the mean fasting plasma glucose and median fasting C-peptide levels were 105.4 ± 13.9 mg/dL and 1.4 [0.8, 2.1] ng/mL, respectively. Insulin degludec being the most commonly administered (279 [50.9%]). The mean 2-hr postprandial glucose was 206.3 ± 64.8 mg/dL, with 350 (63.9%) having 2-hr postprandial glucose &amp;gt; 180 mg/dL. The administered insulin dose was 0.35 ± 0.17 units/kg/day, and 101 (18.4%) had an insulin dose &amp;gt; 0.5 units/kg/day. Conclusion: In East Asian patients with type 2 diabetes receiving basal insulin, although high 2-hr postprandial glucose levels suggest the possibility of overbasalization, the administered dosage of basal insulin was relatively low. Considering the lower insulin secretion capacity in East Asians, it is thought that new, specific criteria for overbasalization in East Asians are necessary. Presentation: 6/3/2024

7518 A Case of Delayed Diagnosis of Acromegaly Associated with Uncontrolled Diabetes

Abstract Disclosure: A. Mahmoudabadi: None. S. Patel: None. Background: Acromegaly is a rare disorder characterized by an excess secretion of growth hormone (GH) and increased circulating insulin-like growth factor 1 (IGF-1) levels, typically due to a GH-secreting pituitary adenoma. This consequently leads to complications such as acral and soft tissue overgrowth, visual disturbance, insulin resistance, and dyslipidemia. In this case, we describe a patient who presented to the endocrinology clinic for uncontrolled diabetes and was subsequently diagnosed with acromegaly. Clinical Case: This is a 47-year-old male with a history of heart failure, hypertension, and type 2 diabetes mellitus (DM) who presented to the clinic with uncontrolled DM. He had failed to achieve adequate blood sugar control despite being compliant with metformin, dapagliflozin, and insulin degludec. Physical examination revealed frontal bossing, prognathism, macroglossia, and a deep voice. On further questioning, he had noticed these changes since five years prior. Anthropometry and laboratory tests were as follows: Height, 180 cm; body weight 107.5 kg; body mass index (BMI), 33.05 kg/m2 and A1c level of 15.0%. Suspicion of acromegaly was confirmed based on biochemical and imaging findings. Fasting growth hormone (GH), at 58 mU/L (reference range 0-10), and insulin-like growth factor 1 (IGF-1), at 857 nmol/L (reference range 81-263), were markedly elevated. Pituitary magnetic resonance imaging (MRI) showed a sellar and suprasellar mass (2.6 × 2.2 × 2.2 cm) extending and compressing the optic chiasm. He eventually underwent a transsphenoidal adenomectomy with neurosurgery. Following surgery, his insulin requirements went from a total daily dose of about 100 units to an inpatient dose of 30 units by his last day of admission. Conclusion: Acromegaly is prevalent in less than 3% of patients with DM, but higher rates of DM are seen in acromegalic patients with higher IGF-1 levels and longer duration of disease. The diagnosis of acromegaly can often be delayed due to missed findings on routine physical examination. This can lead to increased morbidity, mortality, and complications such as uncontrolled DM, witnessed in our patient. Surgical management of acromegaly is the mainstay of treatment and can lead to improvement of glycemic control and insulin sensitivity. Fortunately, our patient could undergo surgery, but delayed diagnosis can prevent patients from surgery if the pituitary tumor becomes too large or unresectable. Ultimately, this case highlights the importance of a thorough physical examination and keeping a wide differential diagnosis when evaluating patients with uncontrolled DM, as failure to diagnose acromegaly at an early stage may have devastating consequences on patient outcomes. Presentation: 6/3/2024

Improved treatment satisfaction with once-weekly insulin icodec compared with once-daily basal insulin in individuals with type 2 diabetes: An analysis of patient-reported outcomes and participant interviews from ONWARDS 2 and 5 and a physician survey from ONWARDS 1

AimsThe ONWARDS phase 3a clinical trials evaluated once-weekly insulin icodec (icodec) versus once-daily basal insulin in type 2 diabetes. This analysis investigated the treatment-related experiences of participants from ONWARDS 5 and 2, and physicians from ONWARDS 1. MethodsPatient-reported outcomes were only collected during ONWARDS 5 (icodec with a dosing guide app vs. once-daily basal analogues) and 2 (icodec vs. once-daily insulin degludec). ONWARDS 1 (icodec vs. once-daily insulin glargine U100) physicians’ treatment preferences and satisfaction were obtained via an online survey. ResultsIn ONWARDS 5 and 2, there was a statistically significantly greater increase in total treatment satisfaction from baseline to end of treatment for icodec/icodec with app versus once-daily comparators, mostly driven by participants’ willingness to continue and recommend treatment. In ONWARDS 2, 93.7 % of icodec users preferred once-weekly over once-daily basal insulin, mainly owing to less frequent injections and ease of use. ONWARDS 1 physicians reported greater satisfaction with once-weekly than with once-daily basal insulin and were more likely to recommend once-weekly injections. ConclusionsThese results demonstrate improved treatment satisfaction with, and strong preferences for, once-weekly versus once-daily basal insulin. Treatment convenience and willingness to continue and recommend once-weekly basal insulin treatment were highlighted.Clinical trial registrations: ONWARDS 1: NCT04460885; ONWARDS 2: NCT04770532; ONWARDS 5: NCT04760626

Efficacy and safety of once-weekly insulin icodec versus once-daily basal insulin in Japanese individuals with type 2 diabetes: A subgroup analysis of the ONWARDS 1, 2 and 4 trials.

To explore the efficacy and safety of once-weekly insulin icodec (icodec) in Japanese adults (≥20 years old) with type 2 diabetes from the global ONWARDS 1, 2 and 4 trials. Insulin-naive (ONWARDS 1) and insulin-experienced (ONWARDS 2 and 4) individuals were randomized to icodec or a once-daily insulin comparator: insulin glargine U100 [ONWARDS 1 (basal insulin only) and 4 (basal-bolus regimen)] or insulin degludec [ONWARDS 2 (basal insulin only)]. The primary outcome was change in glycated haemoglobin from baseline to end of treatment (EOT) (ONWARDS 1: Week 52; ONWARDS 2 and 4: Week 26). Here, we present the Japanese subgroup results. Similar reductions in glycated haemoglobin from baseline to EOT were observed in each trial for icodec and comparators. The proportion of time in range (blood glucose 3.9-10.0 mmol/L) at EOT was also comparable across treatment groups (time in range: 58%-68%), as was time spent with blood glucose below 3.0 mmol/L (<1.0%). Combined clinically significant (blood glucose <3.0 mmol/L) or severe (requiring external assistance for recovery) hypoglycaemia rates were low, with no severe events (ONWARDS 1 and 2) or a single severe event (ONWARDS 4; icodec group) reported. These results generally aligned with findings from the respective global populations. No new safety issues were identified. Icodec improved glycaemic control to a similar degree as once-daily basal insulin comparators while maintaining low levels of clinically significant or severe hypoglycaemia. The findings support icodec use in Japanese individuals with different levels of type 2 diabetes progression.

Cost-utility analysis and drug pricing of once-weekly insulin icodec versus once-daily insulin degludec for type 2 diabetes patients treated with basal insulin in China.

Insulin icodec is a first once-weekly administration basal insulin analogue for type 2 diabetes. This study aimed to investigate the price range of icodec for type 2 diabetes in the Chinese market, taking insulin degludec as reference. Long-term health outcomes and costs for icodec and degludec were simulated using the United Kingdom Prospective Diabetes Study Outcomes Model (version 2.1) over 40 years from the Chinese healthcare provider's perspective. The efficacy and safety data were obtained from the ONWARDS 2 trial (Switching to once-weekly insulin icodec versus once-daily insulin degludec in individuals with basal insulin-treated type 2 diabetes (ONWARDS 2): a phase 3a, randomised, open label, multicentre, treat-to-target trial). Cost-utility analysis and a binary search were used to investigate the price range of icodec. Sensitivity analyses were performed to verify the robustness of the base-case analysis results. After a 40-year simulation, the quality-adjusted life years (QALY) of icodec and degludec were 10.32 and 10.28 years, respectively. At the initial assumption of the same annual costs of icodec and degludec of $455.40, icodec was the dominant therapy compared with degludec, with higher QALYs and lower total cost. After the binary search, we observed that the annual cost range of icodec was $625.17-$855.25. This cost range was finally adjusted to be $597.66-$736.34 using one-way sensitivity analysis and confirmed using probabilistic sensitivity analysis and scenario analysis. The scenario analysis revealed that the annual cost range of icodec could be $506.70-$736.34 if the price of degludec decreased by 20% in the future. Insulin icodec appears to be more cost effective than degludec if the annual cost of icodec ranges from $597.66 to $736.34 for patients with type 2 diabetes in China.

Why insulin aspart and insulin degludec exhibit distinct release mechanisms

Why insulin aspart and insulin degludec exhibit distinct release mechanisms

EVALUATION OF THE GLYCOREGULATION EFFICACY BEFORE AND AFTER TREATMENT WITH INSULIN DEGLUDEC IN PATIENTS WITH TYPE 2 DIABETES MELLITUS IN THE REPUBLIC OF NORTH MACEDONIA

Patients with type 2 diabetes mellitus (T2DM) who have unsatisfactory glycoregulation with concurrent use of basal insulin and oral hypoglycemics, should be switched to a more intensive therapy regime. To evaluate the efficacy of newly available insulin degludec 70/insulin aspart 30 (IDegAsp), we retrospectively analyzed glycoregulation in 131 patients with T2DM treated with this insulin. All 131 patients were with unsatisfactory glycoregulations, and were switched to IDegAsp from other insulins (except basal-bolus insulin regimen). After a mean period of 11.75±5 months of the treatment with IDegAsp, we found statistically significant improvement in fasting and postprandial glucose levels, and HbA1c (12.5±4.4 vs. 8.8±3.9mmol/l, 13.2±4.6 vs. 9.6±4.1mmol/l, 9.7±1.8 vs. 8.1±1.6%, p&lt;0.01, respectively). The total average daily dose of insulin units (IU) was the same, and there weren’t statistically significant differences in the frequency of hypoglycaemia (p&lt;0.05). From the results, we can conclude that patients with T2DM, who switched to IDegAsp from previous antidiabetic insulin treatment (except basal-bolus insulin regimen) had improved glycaemic control without increased insulin units, and without higher risk for hypoglycemia.

Initiation of Insulin Degludec in Chinese Hospitalized Patients with Type 2 Diabetes - A Single Center's Experience.

The long-acting insulin analogue insulin degludec (IDeg) is increasingly recommended for type two diabetes (T2DM), yet clinical experience in China remains limited. This retrospective study aimed to delineate the initiation strategy for IDeg in Chinese hospitalized patients with T2DM. We retrospectively analyzed 217 Chinese hospitalized patients with T2DM who initiated IDeg from December 2018 to June 2020, calculating the initial dose and examining correlations between clinical characteristics and glucose profiles. The initial IDeg doses ranged from 0.15 to 0.18 IU/kg·d, showing no association with clinical characteristics. During titration, mean blood glucose levels (MEAN) correlated positively with diabetes duration, age, and Glycosylated Hemoglobin (HbA1c), and negatively with body mass index (BMI), triglycerides (TG), and low-density lipoprotein (LDL). The coefficient of variation (CV) in glucose levels correlated positively with HbA1c and negatively with BMI and TG. The mean amplitude of glycemic excursions (MAGE) mirrored these trends, with additional negative correlations to estimated glomerular filtration rate (eGFR) and serum albumin (ALB). Notably, glycemic variability parameters did not correlate with the presence of diabetic ketoacidosis (DKA) at admission. Hypoglycemia was observed in 21 patients, with differences in MEAN and CV during titration being the only significant findings. The initial IDeg dosing was inadequate and not tailored to clinical features, and there were weak correlations between diabetes duration, age, BMI, eGFR, LDL, and ALB levels and glucose profile post-initiation.

Once-weekly insulin efsitora alfa versus once-daily insulin degludec in adults with type 1 diabetes (QWINT-5): a phase 3 randomised non-inferiority trial

Insulin efsitora alfa (efsitora) is a once-weekly basal insulin. This phase 3 study aimed to assess the efficacy and safety of efsitora compared with insulin degludec (degludec) in adults with type 1 diabetes. This randomised, 52-week, parallel-design, open-label, treat-to-target non-inferiority study conducted at 82 global health-care centres, randomly assigned (1:1) adults (ie, those aged ≥18 years) with type 1 diabetes glycated haemoglobin A1c (HbA1c) 7·0-10·0% (53·0-85·8 mmol/mol) to efsitora (n=343) or, degludec (n=349), both in combination with insulin lispro. The primary endpoint was the change in HbA1c from baseline to week-26 (non-inferiority margin=0·4%). The trial was registered at ClinicalTrials.gov (NCT05463744) and is completed. Between Aug 12, 2022, and May 7, 2024, of 893 participants enrolled, 692 (77%) participants were randomly assigned to once-weekly efsitora or once-daily degludec, and 623 (90%) participants completed the study. Mean HbA1c decreased from 7·88% (62·66 mmol/mol) at baseline to 7·41% (57·5 mmol/mol) at week 26 with efsitora and from 7·94% (63·3 mmol/mol) at baseline to 7·36% (56·9 mmol/mol) at week 26 with degludec. Mean HbA1c change from baseline to week 26 was -0·51% with efsitora and -0·56% with degludec (estimated treatment difference 0·052%, 95% CI -0·077 to 0·181; p=0·43), confirming a non-inferiority margin of 0·4% for efsitora compared with degludec. Rates of combined level 2 (<54 mg/dL [3·0 mmol/L]) or level 3 severe hypoglycaemia were higher with efsitora compared with degludec (14·03 vs 11·59 events per patient year of exposure; estimated rate ratio 1·21, 95% CI 1·04 to 1·41; p=0·016) during weeks 0-52, with the highest rates during weeks 0-12. Severe hypoglycaemia incidence was higher with efsitora (35 [10%] of 343) versus degludec (11 [3%] of 349) during weeks 0-52. Overall incidence of treatment-emergent adverse events was similar across treatment groups. One death not related to the study treatment occurred in the degludec group. In adults with type 1 diabetes, once-weekly efsitora showed non-inferior HbA1c reduction compared with daily insulin degludec. Higher rates of combined level 2 or level 3 hypoglycaemia and greater incidence of severe hypoglycaemia in participants treated with efsitora compared with participants treated with degludec might suggest the need for additional evaluation of efsitora dose initiation and optimisation in people with type 1 diabetes. Eli Lilly and Company.

Use of Degludec in Youth With Type 1 Diabetes and Recurrent Diabetic Ketoacidosis

This article describes a pediatric diabetes center quality improvement initiative to switch youth with type 1 diabetes and diabetic ketoacidosis (DKA) from insulin glargine to longer-duration insulin degludec to determine whether this change would reduce DKA recurrence. Overall the change in DKA recurrence with degludec was not statistically significant. However, subgroup analysis showed that race/ethnicity and insurance status were significantly associated with change in DKA rates. The association of degludec and decreased rates of repeat DKA in Hispanics and privately insured individuals require further exploration.

Initiating or switching to insulin degludec/insulin aspart in a real-world population of adults with type 2 diabetes in Australia: results from a prospective, non-interventional study.

Insulin degludec/insulin aspart (IDegAsp) is a fixed-ratio co-formulation of insulin degludec and insulin aspart for the treatment of people with diabetes and suboptimal glycaemic control. Few real-world studies of IDegAsp treatment have been conducted. Here, we report results from the Australian cohort of the global ARISE study of real-world IDegAsp use. To investigate glycaemic control and other clinical outcomes in people with type 2 diabetes (T2D) treated with IDegAsp in a real-world setting in Australia. A total of 183 adults with T2D initiating or switching to IDegAsp in the Australian cohort of the open-label, non-interventional ARISE study were followed for 26-36 weeks from August 2019 to December 2020. IDegAsp was associated with significant reductions from baseline to end of study (EOS) in mean glycated haemoglobin (estimated change -0.8% (95% confidence interval (CI): -1.05 to -0.56; P < 0.0001)), fasting plasma glucose (-1.6 mmol/L (95% CI: -2.49 to -0.63; P = 0.0017)) and body weight (-2.6 kg (95% CI: -3.68 to -1.55; P < 0.0001)). In insulin-experienced patients, the mean total daily insulin dose did not change significantly (estimated change from baseline to EOS 3.8 (95% CI: -3.70 to 11.21; P = 0.3202)). The proportion of patients experiencing hypoglycaemia numerically decreased during the study (non-severe: 14.2-10.9%; nocturnal non-severe: 4.9-2.2%; and severe: 2.2-0%). Initiating or switching to IDegAsp in a real-world population of people with T2D in Australia was associated with significant improvements in glycaemic control and body weight, and numerically lower levels of hypoglycaemia compared with baseline.

Initiating or Switching to Insulin Degludec/Insulin Aspart in Adults With Type 2 Diabetes in the Philippines

Objectives. Blood glucose levels of the majority of Filipino patients with type 2 diabetes (T2D) remain uncontrolled. Insulin degludec/insulin aspart (IDegAsp) is a fixed‑ratio co-formulation of the long‑acting basal insulin degludec and the rapid-acting prandial insulin aspart. The real-world ARISE (A Ryzodeg® Initiation and Switch Effectiveness) study investigated clinical outcomes across six countries in people with T2D who initiated IDegAsp. This publication presents the clinical outcomes of the Filipino cohort from a subgroup analysis of the ARISE study. Methodology. This 26-week, open-label, non-interventional study examined outcomes in adults with T2D initiating or switching to IDegAsp (N=185) from other antidiabetic treatments per local clinical guidance. Results. Compared with baseline, there was a significant improvement in glycated hemoglobin at the end of study (EOS) (estimated difference [ED] −1.4% [95% confidence interval −1.7, −1.1]; P&lt;0.0001). Fasting plasma glucose (ED −46.1 mg/dL [−58.2, −34.0]; P&lt;0.0001) and body weight (ED −1.0 kg [−2.0, −0.1]; P=0.028) were significantly reduced at EOS compared with baseline. IDegAsp was associated with a decrease in the incidence of self-reported healthcare resource utilization. Adverse events were reported in eight (4.3%) participants. Conclusions. Initiating or switching to IDegAsp was associated with improved glycemic control, lower body weight, and lower HRU for people with T2D in the Philippines. No new, unexpected AEs were reported.

Optimization of a mass spectrometric analytical method for the quality assessment of insulin and its analogs.

The principal aim of this study was to optimize analytical methodology based on mass spectrometry for the evaluation of the quality of recombinant human insulin and its analogs. In this study ESI-MS was used to assess the quality of human insulin, short acting insulin analogs, insulin lispro, insulin aspart and insulin glulisine and long acting analogs including insulin glargine, insulin degludec, and insulin detemir, in respective pharmaceutical formulations. In this study, with the aimed to optimize analytical conditions, different factors influencing the analytical performance such as pH, ionic strength, sample dilution, organic solvent addition were addressed. The study results demonstrated that MS is a suitable technique for the analysis of biotechnological compounds like insulin and its analogs. Although the obtained results provide an important information regarding this methodology, further studies are needed to validate this analytical approach and check for its suitability to be used in the regulatory environment.