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Background: Degludec insulin liraglutide injection is the world's first and only approved basal insulin GLP-1RA injection in China (GLP-1RA stands for Glucagon-Like Peptide-1 Receptor Agonist. This study aimed to evaluate the long-term cost-effectiveness of IDegLira versus GLP-1RA added to basal insulin regimen (combined regimen) for patients with type 2 diabetes in China., Methods: Based on the perspective of the health system, the study adopts the Swedish Institute for Health Economics diabetes cohort model. The baseline and clinical efficacy data in the model are from the EXTRA study. The cost includes glucose-lowering medication, background treatment cost, and complication treatment costs. The prices of IDegLira and GLP-1RA are based on the national medical insurance payment standards. Insulin adopts the national volume-based procurement average price. Other cost and utility data are sourced from published literature. The health outcome indicator is quality-adjusted life years (QALYs). The simulation time horizon is 30 years. The discounting rate of cost and health outcomes is 5%., Results: In clinical output, IDegLira could reduce the cumulative incidence of various chronic complications in patients compared to the combined regimen. The eye diseases (background, proliferative retinopathy, macular edema, and visual loss) decreased by 24.4%, 41.1%, 18.9%, and 12.2%, respectively. Neuropathy decreased by 17.3%. Proteinuria and end-stage renal disease decreased by 25.9% and 17.6% respectively. Ischemic heart disease, heart failure, and myocardial infarction (stroke) decreased by 0.8%, 1.1%, and 4.7%, respectively. In the base-case analysis, IDegLira compared to the combined regimen shows an incremental cost of -34,254 CNY and an incremental QALYs of 0.436. Under the threshold of 1 times the per capita GDP of China in 2022 (85,698 CNY), IDegLira is a dominant scheme with lower cost and better health outcome. In probabilistic sensitivity analysis, the probability of IDegLira being cost-effective is 100%, indicating that the base-case analysis results are robust., Conclusion: Compared with the combined regimen, the use of IDegLira for Chinese patients with type 2 diabetes can improve long-term health output, save medical costs, and is a dominant scheme., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2025 Xiao et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Aims: 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)., Materials and Methods: 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., Results: At Week 26, 90% of semaglutide and 75% of MDI subjects maintained HbA 1c  ≤7.5% (≤58 mmol/mol) (p = 0.18). Mean changes (95% CI) in HbA 1c , 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., Conclusions: In people with type 2 diabetes well controlled (HbA 1c  ≤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 HbA 1c , lower body weight and lessen the burden of management., (© 2024 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

The advent of once-weekly insulin icodec is a promising development in the care of individuals with diabetes. These once-weekly formulations aimed to improve patient adherence and quality of life for patients who find daily injection administration challenging. Insulin icodec has demonstrated comparable glycemic control to conventionally used daily basal insulins, such as insulin glargine and degludec, in the ONWARDS clinical trials. This approach is aligned with patient-centred guidelines, offers better convenience, and can potentially improve adherence, particularly among older adults with type 2 diabetes and those experiencing distress related to frequent injection administration. However, several challenges persist before widespread adoption is feasible. One main concern is ensuring consistent insulin levels over a full week as fluctuations can lead to an increased risk of hypo- or hyperglycemia. Education, precise dosing, and further research are required to ensure long-term efficacy and safety. Moreover, logistical hurdles, including production costs and supply chain complexities need to be addressed especially in low-resource settings. Future studies should evaluate the broader health impacts of weekly insulin, including cardiovascular outcomes, quality of life, and personalized dosing strategies. Making weekly insulin safe, affordable, and widely available is important to fully realize its potential in diabetes management.

Background: The advantages of insulin degludec 100 U/mL (IDeg100) in the treatment of diabetes mellitus (DM) include consistent release, predictable glucose-lowering effect, and minimal day-to-day variability., Hypothesis/objectives: To describe the use of IDeg100 in dogs with DM, level of diabetic control and adverse effects., Animals: Thirty-three client-owned dogs with DM., Methods: A prospective, multi-institutional, uncontrolled study of newly diagnosed or previously insulin-treated, with or without comorbidities and with or without concurrent medications. Clinical signs and continuous glucose monitoring data were monitored and guided insulin dose adjustments. A per-protocol analysis was performed., Results: The final dose of IDeg100 in dogs was 1.3 U/kg (median, range, 0.4-2.2) achieved in 14 days (median, range, 3-32). Seventy-nine percent (26/33) of the dogs had comorbidities with 42% (11/26) having more than 1 comorbidity. Sixty-four percent (21/33) of dogs were receiving concurrent medications with 62% (13/21) receiving more than 1 non-insulin medication. Seventy-six percent (25/33) were scored as having excellent/very good DM control. From baseline to study exit, dogs showed improvements in both ALIVE DM clinical score (from 3 [0-8, 96.49% CI (2-5)] to 1 [0-7, 96.49% CI (1-2)]; P = .0007) and average 3-day interstitial glucose (from 332.8 ± 68.7 mg/dL, 95% CI [308.8-357.2] to 229.0 ± 56.3 mg/dL [CI 209.0 - 248.9]; P < .0001)., Conclusions and Clinical Importance: Insulin degludec 100 U/mL is effective for the treatment of dogs with DM. Eighty-four percent (28/33) of dogs responded to once daily dose of IDeg100 with low frequency of clinical hypoglycemia., (© 2025 The Author(s). Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

Clinical Impact Ratings: GIM/FP/GP: [Formula: see text] Endocrinology: [Formula: see text]., Competing Interests: Disclosures: Disclosure forms are available with the article online.

Clinical Impact Ratings: Endocrinology: [Formula: see text]., Competing Interests: Disclosures: Disclosure forms are available with the article online.

Aim: 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., Materials and Methods: 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., 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., Conclusion: 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., (© 2024 John Wiley & Sons Ltd.)

In this systematic review and meta-analysis, we compared the efficacy and safety of tirzepatide with those of long-acting or ultra-long-acting insulin for type 2 diabetes. PubMed, Web of Science, Scopus, and Google Scholar were searched from the inception to August 20, 2023. All clinical trials or randomized clinical trials comparing the efficacy of tirzepatide with long-acting or ultra-long-acting insulin for treating type 2 diabetes were included. Three randomized clinical trials, namely SURPASS-3, SURPASS-4, and SURPASS-AP-Combo, with 4339 patients were included. Compared with daily insulin glargine and degludec, once-weekly tirzepatide significantly decreased HbA1c (WMD -1.08%, 95% CI (-1.37, -0.78)), 2h-posprandial blood sugar (BS) (WMD -28.19 mg/dL, 95% CI (-44.98, -11.41)), pre-meal BS (WMD -11.86 mg/dL, 95% CI (-22.83, -0.9)), body weight (WMD -10.61 kg, 95% CI (-13.24, -7.97)), systolic blood pressure (WMD -6.47 mmHg, 95% CI (-8.32, -4.61)), diastolic blood pressure (WMD -2.30 mmHg, 95% CI (-3.05, -1.55)), total cholesterol (WMD -4.78%, 95% CI (-7.05, -2.50)), triglyceride (WMD -14.49%, 95% CI (-19.55, -9.43)), LDL cholesterol (WMD -5.98%, 95% CI (-9.83, -2.13)), and VLDL cholesterol (WMD -14.18%, 95% CI (-19.03, -9.33)) and increased HDL cholesterol (WMD 7.13%, 95% CI (-9.83, -2.13)), with a lower risk of hypoglycemia defined as BS ≤ 70 mg/dL (RR 0.46, 95% CI (0.28, 0.75)). All doses of once-weekly tirzepatide (5 mg, 10 mg, and 15 mg) were superior or non-inferior to insulin. Once-weekly tirzepatide can be a substitution for long-acting insulin in type 2 diabetes with a greater efficacy., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Aim: To evaluate the effect on type 2 diabetes remission of short-term intensive metabolic intervention consisting of frequent dietary, exercise and diabetes management coaching, metformin and fixed-ratio insulin degludec/liraglutide., Methods: In a multicentre open-label randomized controlled trial, insulin-naïve participants within 5 years of diabetes diagnosis were assigned to a 16-week remission intervention regimen or standard care, and followed for relapse of diabetes and sustained remission for an additional year after stopping glucose-lowering drugs., Results: A total of 159 participants aged 57 ± 10 years, with diabetes duration 2.6 ± 1.5 years, body mass index 33.5 ± 6.5 kg/m 2 , and glycated haemoglobin (HbA1c) level 53 ± 7 mmol/mol were randomized and analysed (79 intervention, 80 control). At the end of the 16-week intervention period, compared to controls, intervention participants achieved lower HbA1c levels (40 ± 4 vs. 51 ± 7 mmol/mol; p < 0.0001), and lost more weight (3.3 ± 4.4% vs. 1.9 ± 3.0%; p = 0.02). There was a lower hazard of diabetes relapse overall in the intervention group compared to controls (hazard ratio 0.63, 95% confidence interval [CI] 0.45, 0.88; p = 0.007), although this was not sustained over time. Remission rates in the intervention group were not significantly higher than in the control group at 12 weeks (17.7% vs. 12.5%, relative risk [RR] 1.42, 95% CI 0.67, 3.00; p = 0.36) or at 52 weeks (6.3% vs. 3.8%, RR 1.69, 95% CI 0.42, 6.82) following the intervention period., Conclusions: An intensive remission-induction intervention including fixed-ratio insulin degludec/liraglutide reduced the risk of type 2 diabetes relapse within 1 year without sustained remission., (© 2024 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Aim: 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., Materials and Methods: 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., 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., Conclusions: 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., (© 2024 Novo Nordisk and The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

The impacts of insulin degludec U100 (Deg-100) and insulin glargine U300 (Gla-300) on glycemic variability (GV) in patients with type 1 diabetes, as well as the impact of major nutrient components on GV in these patients, remain unclear. This was an observational, cross-sectional, retrospective study. Type 1 diabetes mellitus patients treated with either Deg-100 or Gla-300 as basal insulin were enrolled. After the participants underwent continuous glucose monitoring, GV indices and major nutrient components were analyzed. Forty patients with type 1 diabetes were enrolled, and 20 participants used Deg-100, and 20 used Gla-300. There was no significant difference in major nutrient components between the two groups. Better GV indices of standard deviation, coefficient of variation, mean amplitude of glycemic excursion, AUC n , M-value, CONGA1, CONGA2, and CONGA4 were noted in the Gla-300 group versus Deg-100 group. Compared with patients who received once-daily injection in the morning (QD), Deg-100 administration once daily at bedtime (HS) yielded a higher low blood glucose index during both day and nocturnal periods, indicating a higher risk of hypoglycemic events. By contrast, there were significantly lower levels of CONGA1, CONGA2, and CONGA4 during insulin Gla-300 QD administration than during HS administration, indicating a lower GV of a short interval. In this real-world study involving type 1 diabetes patients, Gla-300 appears to offer more stable glucose variability than Deg-100. Administering once-daily injections could lower the risk of hypoglycemia in the Deg-100 group and minimize GV in the Gla-300 group compared to bedtime injections., (© 2024 The Author(s). The Kaohsiung Journal of Medical Sciences published by John Wiley & Sons Australia, Ltd on behalf of Kaohsiung Medical University.)

Aims: To investigate glycaemic control in Chinese adults with type 2 diabetes (T2D) initiating, or switching to insulin degludec/insulin aspart (IDegAsp), a co-formulation of basal, and bolus insulin, in a real-world setting., Materials and Methods: A 20-week, prospective, single-arm, open-label, non-interventional study was conducted in Chinese adults with T2D initiating, or switching to IDegAsp after anti-hyperglycaemic treatment with oral antidiabetic drugs (OADs), other insulins, or glucagon-like peptide-1 receptor agonists. The primary endpoint was a change in HbA 1c from baseline to end of the study; the secondary endpoints included a change in fasting plasma glucose and Diabetes Treatment Satisfaction Questionnaire (DTSQ) score., Results: Significant reductions were observed in mean HbA 1c and fasting plasma glucose, among both the overall population (N = 878; -1.27%-points [95% CI: -1.36; -1.19]; p < 0.0001, and -1.61 mmol/L [95% CI: -1.81; -1.41]; p < 0.0001, respectively), and in subgroups switching from OADs only, or basal, or premix insulins ± OADs. The mean total DTSQ score increased from 26.4 (baseline) to 31.6 (end-of-study). No significant, or unexpected tolerability, or safety issues were observed. Significant reductions were observed in incidence rates of non-severe (rate ratio 0.37 [95% CI: 0.24; 0.59]; p < 0.0001) and nocturnal non-severe (rate ratio 0.45 [95% CI: 0.21; 0.94]; p = 0.0326) hypoglycaemic episodes., Conclusions: In a broad, real-world Chinese population of adults with T2D, initiating or switching to IDegAsp was associated with improved glycaemic control and lower rates of hypoglycaemia. The use of IDegAsp could be an effective treatment option for those with suboptimal glycaemic control or therapeutic inertia., (© 2024 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Aims: To evaluate the efficacy and safety of insulin glargine 300 U/mL (Gla-300) in people with uncontrolled type 2 diabetes (T2D) switching from another basal insulin (BI)., Materials and Methods: INITIATION was an interventional, single-arm, phase IV study conducted in China. In this post hoc subpopulation analysis, the efficacy and safety of switching to Gla-300 was investigated in individuals with uncontrolled T2D (HbA1c 7.5%-11.0% [58-97 mmol/mol]) with previous BI. The primary endpoint was HbA1c change at week 24. Other measures of glycaemia, hypoglycaemia, insulin dose and weight change were assessed., Results: Three hundred and two participants switched to Gla-300 from another BI, including 232 from insulin glargine 100 U/mL (Gla-100) and 55 from insulin degludec (IDeg). At week 24, the mean ± standard error (SE) HbA1c change from baseline was -0.87% ± 0.06% (-9.5 ± 0.7 mmol/mol; p <0.001). Significant reductions in fasting plasma glucose (least-squares mean [LSM] change -1.13 mmol/L) and fasting self-measured blood glucose (LSM change -1.36 mmol/L) were also observed (both p <0.001). The mean daily BI dose increased from 18.86 U (0.27 U/kg) at baseline to 28.83 U (0.41 U/kg) at week 24. During the 24-week treatment period, the incidence of any hypoglycaemia was 43.8% for all hypoglycaemia and 15.1% for nocturnal hypoglycaemia; the incidence of severe hypoglycaemia was low (0.7%). Minimal body weight change was documented., Conclusions: Gla-300 improved glycaemic control with a relatively low hypoglycaemia risk and minimal weight gain in Chinese people with T2D uncontrolled on previous BI., (© 2024 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

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., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Aims: The 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., Methods: Patient-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., Results: In 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., Conclusions: These 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., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [WP has acted as a consultant for Abbott Diabetes, Bigfoot, Dexcom, Eli Lilly, Embecta, Insulet, Novo Nordisk, Sanofi and Vertex, and has received research support from Abbott Diabetes and Dexcom. MB, LC and AMD are employees and shareholders of Novo Nordisk A/S. MD has acted as consultant, advisory board member and speaker for Boehringer Ingelheim, Eli Lilly, Novo Nordisk and Sanofi, an advisory board member for Pfizer and Zealand Pharma, and a speaker and advisory board member for AstraZeneca. She has received grants from AstraZeneca, Boehringer Ingelheim, Eli Lilly, Janssen, Novo Nordisk and Sanofi-Aventis. EF has acted as a speaker for AstraZeneca, Bioton, Boehringer Ingelheim, Eli Lilly, Krka, Novo Nordisk, Sanofi and Zentiva. MK has received honoraria for speaker’s bureau or advisory board attendance from Abbott Diabetes Care, AstraZeneca, Bayer AG, Boehringer Ingelheim, Eli Lilly, MSD, Novo Nordisk and Sanofi, and has also participated in randomised controlled trials funded by AstraZeneca, Eli Lilly and Novo Nordisk. AP-T performs research and serves as an adviser on behalf of their employer for Abbott, Dexcom, Eli Lilly, Medtronic, Novo Nordisk and Sanofi; there has been no direct or indirect transfer of funds. RG reports research fees paid to his institution by AstraZeneca, Boehringer Ingelheim, Eli Lilly, Janssen, Novo Nordisk and Sanofi, and lecture honoraria and consulting fees from Boehringer Ingelheim, Eli Lilly, Janssen, Novo Nordisk and Sanofi]., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: Alleviation of unrecognized glucotoxicity, with resultant recovery of β-cell function, could amplify the glucose-lowering effect of pharmacotherapy and contribute to the variable therapeutic response observed among patients with type 2 diabetes (T2D). However, clinical evidence supporting this concept is lacking. Short-term intensive insulin therapy (IIT) can ameliorate glucotoxicity and improve β-cell function in early T2D. Thus, for evidence of recovery of glucotoxicity-associated β-cell dysfunction, we sought to determine whether there exists a baseline fasting glucose threshold above which the post-IIT improvement in both β-cell function and glycemia is amplified., Research Design and Methods: IIT (glargine, lispro) was administered for 3 weeks to 108 adults with T2D (mean duration 1.8 ± 1.4 years). Oral glucose tolerance tests before and after IIT enabled assessment of β-cell function by Insulin Secretion-Sensitivity Index-2 and insulinogenic index/HOMA-insulin resistance. For each level of baseline fasting glycemia from 6.0 to 10.5 mmol/L, we modeled the difference in IIT-induced percentage change in β-cell function between those at/above the indicated glucose level and those below it., Results: The relationship between baseline fasting glucose and the differential change in β-cell function was nonlinear. Instead, this relationship was best fit by a cubic regression model with inflection (amplification) at fasting glucose at 9.3 mmol/L. Moreover, baseline fasting glucose at 9.3 mmol/L also identified the inflection point at which nonlinear reductions in fasting glucose and 2-h glucose, respectively, were both amplified., Conclusions: The respective improvements in β-cell function and glycemia in response to short-term IIT are amplified in those in whom baseline fasting glucose exceeds a defined threshold, consistent with reversal of glucotoxicity., (© 2024 by the American Diabetes Association.)

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, C max , AUC 0-12 and GIR-AUC 0-24 decreased whereas AUC 24-96 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., (© 2024. The Author(s).)

Aims: To summarize the results of clinical studies of insulin icodec, an investigational insulin analog designed for once-weekly administration, in adults with type 1 and type 2 diabetes., Methods: Thirteen published articles describing clinical studies of insulin icodec were identified in PubMed, and data pertinent to key study outcomes were selected for inclusion in this review., Results: In insulin-naïve and insulin-treated individuals, icodec demonstrated efficacy in glycaemic control superior or noninferior to that of insulins glargine U100, glargine U300 and degludec. Icodec exhibited a safety profile comparable to marketed insulins, with the exception of hypoglycaemic event rates., Conclusions: As a once-weekly alternative to daily basal insulin, icodec is expected to improve patient adherence and satisfaction, reducing the required number of injections per year from 365 to 52 and providing a dosing option potentially attractive to a wide range of insulin users. However, clinical data suggest a notable risk of hypoglycaemia with weekly icodec administration, especially in individuals with type 1 diabetes., (© 2024 Diabetes UK.)

Background: 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., Aims: 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., Methods: 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., Results: 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%)., Conclusions: 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., (© 2024 The Author(s). Internal Medicine Journal published by John Wiley & Sons Australia, Ltd on behalf of Royal Australasian College of Physicians.)

Objective: To compare the efficacy and safety of insulin degludec biosimilar B01411 (HS-IDeg) with originator insulin degludec-Tresiba (NN-IDeg) in Chinese patients with type 2 diabetes mellitus (T2DM) who were inadequately controlled on oral antidiabetic drugs (OADs) for at least 3 months., Methods: This multicenter, randomized, open-label, parallel-group, active-controlled, phase 3 study enrolled 362 participants with T2DM. Participants were stratified according to whether the insulin secretagogue (sulfonylurea or glinide) had been used before the screening and then randomized 1:1 to receive once-daily subcutaneous injections of HS-IDeg ( n  = 180) or NN-IDeg ( n  = 182) for 18 weeks. The primary endpoint was the change from baseline in glycated hemoglobin (HbA 1c ) to week 18., Results: At week 18, the least squares (LS) mean change in HbA 1c from baseline was -1.34% (95% CI -1.47 to -1.21) and -1.25% (95% CI -1.38 to -1.12) with HS-IDeg and NN-IDeg, respectively. The LS mean difference (HS-IDeg minus NN-IDeg) in HbA 1c at week 18 was -0.09% (95% CI -0.28 to 0.10), demonstrating non-inferiority of HS-IDeg to NN-IDeg. Participants achieving HbA 1c <7.0% at week 18 were 34.5% and 29.5% with HS-IDeg and NN-IDeg, respectively. Mean decreases in fasting plasma glucose and standard deviation of blood glucose were similar between both groups. Safety and tolerability, including hypoglycemia, adverse events, and weight change were similar between both groups. No severe hypoglycemia and no death occurred in the study., Conclusions: HS-IDeg and NN-IDeg demonstrated similar efficacy and safety over 18 weeks of treatment in Chinese patients with T2DM who had inadequate responses to OADs for at least 3 months.

Background: 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., Methods: 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 A 1c (HbA 1c ) 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 HbA 1c from baseline to week-26 (non-inferiority margin=0·4%). The trial was registered at ClinicalTrials.gov (NCT05463744) and is completed., Findings: 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 HbA 1c 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 HbA 1c 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., Interpretation: In adults with type 1 diabetes, once-weekly efsitora showed non-inferior HbA 1c 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., Funding: Eli Lilly and Company., Competing Interests: Declaration of interests RMB has received research support from, consulted, or has been on a scientific advisory board for Abbott Diabetes Care, Ascensia, Bigfoot Biomedical, CeQur, Dexcom, Eversense, Hygieia, Insulet, Eli Lilly and Company, Medtronic, Novo Nordisk, Onduo, Roche Diabetes Care, Sanofi, Tandem Diabetes Care, United Healthcare, Vertex Pharmaceutical, and Zealand Pharma. His technology research is funded in part by the National Institute of Diabetes and Digestive and Kidney Diseases and Helmsley Charitable Trust. RMB's employer, non-profit HealthPartners Institute, contracts him for his services, and no personal income from any of these activities goes directly to him. RSW has participated in multicentre clinical trials, through her institution, sponsored by Eli Lilly and Company, Insulet, Tandem, Amgen, MannKind, NovoNordisk, Wolters Kluwer, and Diasome, and has used Dexcom devices obtained at reduced cost in clinical research studies. CM serves or has served on advisory panels for Novo Nordisk, Sanofi, Eli Lilly and Company, Dexcom, Boehringer Ingelheim, Bayer, Roche, Medtronic, Imcyse, Insulet, Biomea Fusion, ActoBio Therapeutics, AstraZeneca, and Vertex. Financial compensation for these activities has been received by KU Leuven; KU Leuven has received research support for CM from Medtronic, Novo Nordisk, Sanofi, and ActoBio Therapeutics. CM serves or has served on the speaker's bureau for Novo Nordisk, Sanofi, Eli Lilly and Company, Medtronic, and Boehringer Ingelheim. Financial compensation for these activities has been received by KU Leuven. YO has received speaker's bureau fees from Eli Lilly, Novo Nordisk, and Sumitomo Pharma. AMC, MLK, MCC, and VV are employees and shareholders of Eli Lilly and Company., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Aim: To compare the effectiveness of different basal insulins (BI) prescribed as an add-on to or switch from glucagon-like peptide-1 receptor agonist (GLP-1 RA) therapy., Materials and Methods: Retrospective, real-world data from electronic medical records of 32 Italian diabetes clinics were used, after propensity score adjustment, to compare effectiveness after 6 months of treatment with second- versus first-generation BI (2BI vs. 1BI) or glargine 300 U/ml versus degludec 100 U/ml (Gla-300 vs. Deg-100), when added to (ADD-ON) or in substitution of (SWITCH) GLP-1 RA. Only comparisons, including a minimum of 100 patients per group, were performed to ensure adequate robustness of the analyses., Results: In the ADD-ON cohort (N = 700), greater benefits of 2BI versus 1BI were found in glycated haemoglobin {HbA1c; estimated mean difference: -0.32% [95% confidence interval (CI) -0.62; -0.02]; p = .04} and fasting blood glucose [FBG; -20.73 mg/dl (95% CI -35.62; -5.84); p = .007]. In the SWITCH cohort (N = 2097), greater benefits of 2BI versus 1BI were found in HbA1c [-0.22% (95% CI -0.42; -0.02); p = .03], FBG [-10.15 mg/dl (95% CI -19.04; -1.26); p = .03], and body weight [-0.67 kg (95% CI -1.30; -0.04); p = .04]. In the SWITCH cohort starting 2BI (N = 688), marked differences in favour of Gla-300 versus Deg-100 were documented in HbA1c [-0.89% (95% CI -1.26; -0.52); p < .001] and FBG [-17.89 mg/dl (95% CI -32.45; -3.33); p = .02]. Using propensity score matching as a sensitivity analysis, the benefit on HbA1c was confirmed [-0.55% (95% CI -1.02; -0.08); p = .02]. BI titration was suboptimal in all examined cohorts., Conclusions: 2BI are a valuable option to intensify GLP-1 RA therapy. Switching to Gla-300 versus Deg-100 was associated with greater HbA1c improvement., (© 2024 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Aim: To perform a participant-level post hoc meta-analysis of Phase 3a trials in type 2 diabetes (T2D) to characterize the hypoglycaemia safety and glycaemic efficacy of once-weekly insulin icodec (icodec)., Materials and Methods: All ONWARDS 1-5 randomized participants were pooled as overall T2D, insulin-naive, an insulin-experienced subgroups, and by once-daily trial comparator (degludec or glargine U100). The main outcomes included incidence and rates of clinically significant and severe hypoglycaemia. Additional endpoints included change in glycated haemoglobin (HbA1c) from baseline and HbA1c target achievement without clinically significant or severe hypoglycaemia., Results: The meta-analysis comprised 3765 participants (1882 icodec vs. 1883 comparators). In the overall T2D pool, clinically significant hypoglycaemia incidence was similar in the icodec group versus the comparator group (17.9% vs. 16.2%, odds ratio [OR] 1.14, 95% confidence interval [CI] 0.94, 1.38); however, rates were low but significantly higher in the icodec group (1.15 vs. 1.00 episodes/participant-year of exposure, estimated rate ratio 1.51 [95% CI 1.24, 1.85]). Fewer severe hypoglycaemic episodes occurred with icodec than with comparators (8 vs. 18). A greater reduction in HbA1c occurred with icodec versus comparators, irrespective of subgroup (estimated treatment difference range [-0.10 to -0.29%]; all p < 0.05). Across subgroups, except for the insulin-experienced subgroup, the odds of achieving HbA1c <53 mmol/mol (7.0%) without clinically significant or severe hypoglycaemia were greater with icodec than with comparators (OR range 1.30-1.55; all p < 0.05)., Conclusions: Icodec was associated with a similar incidence but higher rates of clinically significant hypoglycaemia (equating to one additional hypoglycaemic episode every 6 years) and fewer severe hypoglycaemic episodes versus comparators. Our findings also confirmed the greater efficacy of icodec that was demonstrated in the ONWARDS trial programme., (© 2024 Novo Nordisk A/S and The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Insulin icodec (AWIQLI ® ) is an ultra-long-acting basal insulin analogue that is being developed by Novo Nordisk for the treatment of diabetes mellitus. Administered once weekly as a subcutaneous injection, insulin icodec is designed to improve treatment adherence and glycaemic control relative to once-daily insulin analogues. On 7 March 2024, insulin icodec was approved in Switzerland for the treatment of diabetes mellitus in adults. Insulin icodec was approved in Canada on 12 March 2024 for the once-weekly treatment of adults with diabetes mellitus to improve glycaemic control and received EU approval in May 2024 for the treatment of diabetes mellitus in adults. This article summarizes the milestones in the development of insulin icodec leading to this first approval for diabetes mellitus., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Aim: To compare the efficacy and safety of a fixed-ratio combination of insulin glargine 100 U/mL plus lixisenatide (iGlarLixi) with premixed insulin, insulin degludec plus insulin aspart (IDegAsp), in Chinese people with type 2 diabetes (T2D) suboptimally controlled with oral antidiabetic drug(s) (OADs)., Methods: In Soli-D, a 24-week, multicentre, open-label, study, insulin-naïve adults were randomized 1:1 to once-daily injections of iGlarLixi (n = 291) or IDegAsp (n = 291), with continued metformin ± sodium-glucose co-transporter-2 inhibitors. The primary endpoint was non-inferiority in HbA1c change from baseline to week 24. Key secondary endpoints included superiority in HbA1c change and body weight (BW) change at week 24. Hypoglycaemia rates were also assessed., Results: At week 24, iGlarLixi showed non-inferiority and superiority over IDegAsp in HbA1c reduction (least squares [LS] mean difference: -0.20 [95% confidence interval {CI}: -0.33, -0.07]; P < .001 for non-inferiority; [97.5% CI: -0.35, -0.05]; P = .003 for superiority). iGlarLixi decreased BW and IDegAsp increased BW from baseline to week 24, with a statistically significant LS mean difference of -1.49 kg in favour of iGlarLixi (97.5% CI: -2.32, -0.66; P < .001). Event rates (per person-year) for American Diabetes Association (ADA) Level 1, 2 or 3 hypoglycaemia were lower for iGlarLixi (1.90) versus IDegAsp (2.72) (relative risk: 0.71; 95% CI: 0.52, 0.98). No ADA Level 3 hypoglycaemia or unexpected safety findings were reported., Conclusions: In Chinese people with T2D suboptimally controlled with OADs, once-daily iGlarLixi provided better glycaemic control with BW benefit and lower hypoglycaemia event rates versus IDegAsp., (© 2024 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Backgruound: This study investigated the real-world efficacy and safety of insulin degludec/insulin aspart (IDegAsp) in Korean adults with type 2 diabetes mellitus (T2DM), whose insulin treatment was switched to IDegAsp., Methods: This was a multicenter, retrospective, observational study comprising two 26-week treatment periods, before and after switching to IDegAsp, respectively. Korean adults with uncontrolled T2DM treated with basal or premix insulin (±oral antidiabetic drugs) were enrolled. The primary objective was to compare the degree of glycosylated hemoglobin (HbA1c) change in each 26-week observation period. The analyses included changes in HbA1c, fasting plasma glucose (FPG), body weight, proportion of participants achieving HbA1c <7.0%, hypoglycemic events, and total daily insulin dose (ClinicalTrials.gov, number NCT04656106)., Results: In total, 196 adults (mean age, 65.95 years; mean T2DM duration, 18.99 years) were analyzed. The change in both HbA1c and FPG were significantly different between the pre-switching and the post-switching period (0.28% vs. -0.51%, P<0.001; 5.21 mg/dL vs. -23.10 mg/dL, P=0.005), respectively. After switching, the rate of achieving HbA1c <7.0% was significantly improved (5.10% at baseline vs. 11.22% with IDegAsp, P=0.012). No significant differences (before vs. after switching) were observed in body weight change, and total daily insulin dose. The rates of overall and severe hypoglycemia were similar in the two periods., Conclusion: In real-world clinical practice in Korea, the change of insulin regimen to IDegAsp was associated with an improvement in glycemic control without increase of hypoglycemia, supporting the use of IDegAsp for patients with T2DM uncontrolled with basal or premix insulin.

Despite the availability of new classes of glucose-lowering drugs that improve glycaemic levels and minimise long-term complications, at least 20-25% of people with type 2 diabetes require insulin therapy. Moreover, a substantial proportion of these individuals do not achieve adequate metabolic control following insulin initiation. This is due to several factors: therapeutic inertia, fear of hypoglycaemia and/or weight gain, poor communication, complexity of insulin titration, and the number of injections needed, with the associated reduced adherence to insulin therapy. Once-weekly insulins provide a unique opportunity to simplify basal insulin therapy and to allow good glycaemic control with a low risk of hypoglycaemia. Several approaches to developing a stable and effective once-weekly insulin have been proposed, but, to date, insulin icodec and basal insulin Fc (insulin efsitora alfa) are the only two formulations for which clinical studies have been reported. The results of Phase I and II studies emphasise both efficacy (in term of glucose levels) and potential risks and adverse events. Phase III studies involving insulin icodec are reassuring regarding the risk of hypoglycaemia compared with daily basal insulin analogues. Despite some concerns raised in ongoing clinical trials, the available data suggest that weekly insulins may also be an option for individuals with type 1 diabetes, especially when adherence is suboptimal. For the first time there is an opportunity to make an important breakthrough in basal insulin therapy, particularly in people with type 2 diabetes, and to improve not only the quality of life of people with diabetes, but also the practice of diabetologists., (© 2024. The Author(s).)

Aims: Insulin efsitora alfa (efsitora) is a once-weekly basal insulin. This review describes the study design and rationale of the efsitora phase 3 Once Weekly (QW) Insulin Therapy (QWINT) clinical development programme, including the five trials, QWINT-1 through QWINT-5., Materials and Methods: The five trials included insulin-naïve adults (QWINT-1 and -2) with type 2 diabetes (T2D), adults with T2D previously treated with basal insulin (QWINT-3 and -4), and QWINT-5 in adults with type 1 diabetes. All five trials were designed as multicentre, randomized, controlled, open-label, treat-to-target studies to investigate the efficacy and safety of efsitora versus active once-daily basal insulin comparators (insulin glargine U100 or insulin degludec U100). The primary objective of each trial is to compare the change in HbA1c from baseline to week 26 or 52 between efsitora and the active comparator. The key secondary objectives include change in fasting glucose, insulin dose and continuous glucose monitoring variables, and patient-reported outcome questionnaires., Conclusions: The QWINT development programme includes a racially and geographically diverse population to provide important information regarding the efficacy and safety of efsitora and its clinical management of people with diabetes., (© 2024 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Context: Limited evidence is available on the real-world effect of insulin degludec (IDeg) in type 1 diabetes (T1D), using continuous glucose monitoring (CGM)-derived metrics. Objective: To assess the real-world effect of switching to IDeg from other long-acting insulins on time in ranges (TIRs) measured by CGM, metabolic control, and insulin dose for people with T1D. Design: This retrospective multicenter study encompassed five time points during a 12-month pre-switch of IDeg and a 12-month follow-up period. For each visit, clinical and CGM data were collected to evaluate temporal trends in glycemic outcomes. Participants: Of 753 persons with T1D who were assessed for eligibility, 486 persons were included, mostly men (61.5%), 47.4 (16.9) years old and diabetes duration of 23.8 (14.2) years at IDeg-initiation. Main Outcome Measure: Primary outcome was the evolution of percent TIR (70-180 mg/dL or 3.9-10.0 mmol/L, TIR) before versus after switch to IDeg. Results: TIR over 24 h increased at 12 months versus baseline (56.7% vs. 52.3%, P  < 0.001), mostly during daytime. Time <54 mg/dL (<3.0 mmol/L) over 24 h decreased at 12 months versus baseline (2.02% vs. 2.86%, P  < 0.001), mostly during nighttime. Glycated hemoglobin (7.9% vs. 8.1%, P  < 0.001) and coefficient of variation (40.0% vs. 41.5%, P  < 0.001) improved at 12 months versus baseline. Mean daily basal, bolus and total insulin doses decreased at 12 months ( P  < 0.001 for all vs. baseline). Conclusions: This retrospective real-world study reports that switching basal insulin significantly improved time spent in glucometric ranges and glycemic variability in the studied population of people with T1D. Clinical Trial Registration number: NCT05434559.

Background and Aims: Add-on of basal insulin (BI) to intensify the ongoing therapy with glucagon-like peptide 1 receptor agonist (GLP-1 RA) is recommended, but it is unclear if free or fixed combination of BI and GLP-1 RA produce similar outcomes. A retrospective comparative effectiveness analysis of the add-on of glargine 300 U/mL (Gla-300) to ongoing GLP-1 RA vs. switch to fixed ratio combination of degludec and liraglutide (iDegLira) was performed., Methods and Results: Real-world data collected in electronic medical records by 32 Italian diabetes clinics. Propensity score (PS) adjustment was applied to assess changes in glycated hemoglobin (HbA1c), fasting blood glucose (FBG), body weight, and BI dose after 6 months from Gla-300 or iDegLira initiation. Compared to iDegLira group (N = 260), Gla-300+GLP-1 RA group (N = 255) had older age and higher levels of HbA1c (9.1 vs. 8.9%). After 6 months, statistically significant greater FBG improvement [estimated mean difference and 95% confidence intervals: -24.05 mg/dl (-37.04; -11.06; p = 0.0003) and BI dose increase [+0.03 U/kg (95%CI 0.00; 0.06); p = 0.009] were found in the free vs. fixed combination group, although low doses of BI (0.2 U/kg) were reached in both groups. Trends of larger HbA1c and body weight reductions with the free combination were also found, without reaching the statistical significance., Conclusion: Although inertia in insulin initiation and titration was documented in both groups, higher benefit on FBG control was obtained with free vs. fixed combination, likely due to a better titration of BI and GLP-1 RA., Competing Interests: Declaration of competing interest Riccardo Candido has received consultancy fees from Boehringer Ingelheim, Eli-Lilly, Novo Nordisk, Astra-Zeneca, Sanofi-Aventis, Roche Diabetes Care; speaking fees from Astra Zeneca, Boehringer Ingelheim, Eli-Lilly, Novo Nordisk, Sanofi-Aventis, Mundipharma Pharmaceutical, Abbott, MSD, Neopharmed Gentili, Menarini, Essex Italia, Ascensia Diabetes. Antonio Nicolucci and Maria Chiara Rossi have received funding for research from Sanofi, NovoNordisk, Alfasigma, Artsana, AstraZeneca, Johnson&Johnson, Medtronic, Shionogi, SOBI, Meteda and Theras. Monica Larosa is an employee of Sanofi and may hold shares and/or stock options in the company. Raffaele Napoli has served on advisory board panels, received consultancy and speaker's fees or financial support for research from AstraZeneca, Boerhinger Ingelheim, Eli Lilly, Novo Nordisk, MSD, Sanofi., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background and Aims: IDegAsp (Ryzodeg 70/30), a unique premixed formulation of long-acting insulin degludec and rapid-acting insulin aspart, is increasing in use. Management of IDegAsp during hospitalisation is challenging because of degludec's ultra-long duration of action. We investigated inpatient glycaemia in patients treated with IDegAsp compared to biphasic insulin aspart (BIAsp30; Novomix30)., Methods: We performed a retrospective observational study at two hospitals assessing inpatients with type 2 diabetes treated with IDegAsp or BIAsp30 prior to and during hospital admission. Standard inpatient glycaemic outcomes were analysed based on capillary blood glucose (BG) measurements., Results: We assessed 88 individuals treated with IDegAsp and 88 HbA1c-matched individuals treated with BIAsp30. Patient characteristics, including insulin dose at admission, were well matched, but the IDegAsp group had less frequent twice-daily insulin dosing than the BIAsp30 group (49% vs 87%, P < 0.001). Patient-days with BG <4 mmol/L were not different (10.6% vs 9.9%, P = 0.7); however, the IDegAsp group had a higher patient-day mean BG (10.4 (SD 3.4) vs 10.0 (3.4) mmol/L, P < 0.001), and more patient-days with mean BG >10 mmol/L (48% vs 38%, P < 0.001) compared to the BIAsp30 group. Glucose was higher in the IDegAsp group in the evening (4 PM to midnight) (11.6 (SD 4.0) vs 10.9 (4.6) mmol/L, P = 0.004), but not different at other times during the day., Conclusions: Inpatients treated with IDegAsp compared to BIAsp30 had similar hypoglycaemia incidence, but higher hyperglycaemia incidence, potentially related to less frequent twice-daily dosing. With the increasing use of IDegAsp in the community, development of hospital management guidelines for this insulin formulation is needed., (© 2024 The Authors. Internal Medicine Journal published by John Wiley & Sons Australia, Ltd on behalf of Royal Australasian College of Physicians.)

Aim: To evaluate whether caffeine combined with a moderate amount of glucose reduces the risk for exercise-related hypoglycaemia compared with glucose alone or control in adult people with type 1 diabetes using ultra-long-acting insulin degludec., Materials and Methods: Sixteen participants conducted three aerobic exercise sessions (maximum 75 min) in a randomized, double-blind, cross-over design. Thirty minutes before exercise, participants ingested a drink containing either 250 mg of caffeine + 10 g of glucose + aspartame (CAF), 10 g of glucose + aspartame (GLU), or aspartame alone (ASP). The primary outcome was time to hypoglycaemia., Results: There was a significant effect of the condition on time to hypoglycaemia (χ 2  = 7.674, p = .0216). Pairwise comparisons revealed an 85.7% risk reduction of hypoglycaemia for CAF compared with ASP (p = .044). No difference was observed between GLU and ASP (p = .104) or between CAF and GLU (p = .77). While CAF increased glucose levels during exercise compared with GLU and ASP (8.3 ± 1.9 mmol/L vs. 7.7 ± 2.2 mmol/L vs. 5.8 ± 1.4 mmol/L; p < .001), peak plasma glucose levels during exercise did not differ between CAF and GLU (9.3 ± 1.4 mmol/L and 9.1 ± 1.6 mmol/L, p = .80), but were higher than in ASP (6.6 ± 1.1 mmol/L; p < .001). The difference in glucose levels between CAF and GLU was largest during the last 15 min of exercise (p = .002). Compared with GLU, CAF lowered perceived exertion (p = .023)., Conclusions: Pre-exercise caffeine ingestion combined with a low dose of glucose reduced exercise-related hypoglycaemia compared with control while avoiding hyperglycaemia., (© 2024 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Objective: The Padova type 2 diabetes (T2D) simulator (T2DS) has been recently proposed to optimize T2D treatments including novel long-acting insulins. It consists of a physiological model and an in silico population describing glucose dynamics, derived from early-stage T2D subjects studied with sophisticated tracer-based experimental techniques. This limits T2DS domain of validity to this specific sub-population. Conversely, running simulations in insulin-naïve or advanced T2D subjects, would be more valuable. However, it is rarely possible or cost-effective to run complex experiments in such populations. Therefore, we propose a method for tuning the T2DS to any desired T2D sub-population using published clinical data. As case study, we extended the T2DS to insulin-naïve T2D subjects, who need to start insulin therapy to compensate the reduced insulin function., Methods: T2DS model was identified based on literature data of the target population. The estimated parameters were used to generate a virtual cohort of insulin-naïve T2D subjects (inC1). A model of basal insulin degludec (IDeg) was also incorporated into the T2DS to enable basal insulin therapy. The resulting tailored T2DS was assessed by simulating IDeg therapy initiation and comparing simulated vs. clinical trial outcomes. For further validation, this procedure was reiterated to generate a new cohort of insulin-naïve T2D (inC2) assuming inC1 as target population., Results: No statistically significant differences were found when comparing fasting plasma glucose and IDeg dose, neither in clinical data vs. inC1, nor inC1 vs. inC2., Conclusions: The tuned T2DS allowed reproducing the main findings of clinical studies in insulin-naïve T2D subjects., Significance: The proposed methodology makes the Padova T2DS usable for supporting treatment guidance in target T2D populations.

Objective: This post hoc analysis assessed change from baseline to week 52 in glycemic parameters for tirzepatide (5, 10, 15 mg) versus insulin degludec (SURPASS-3 trial) and glargine (SURPASS-4 trial) in people with type 2 diabetes and different baseline glycemic patterns, based on fasting serum glucose (FSG) and postprandial glucose (PPG) values., Research Design and Methods: Participant subgroups with low FSG/low PPG, low FSG/high PPG, high FSG/low PPG, and high FSG/high PPG were defined according to the median values of these measures., Results: All tirzepatide doses and basal insulins were associated with decreased HbA1c, FSG, and PPG values from baseline to week 52 in all subgroups (P < 0.05). Within each subgroup, HbA1c and PPG decreases were greater with tirzepatide than insulin (P < 0.05). FSG decreases were generally similar. There were no differential treatment effects by FSG/PPG subgroup., Conclusions: In this post hoc analysis, tirzepatide was associated with superior glycemic control compared with insulin, irrespective of baseline glycemic pattern., (© 2024 by the American Diabetes Association.)

Objective: This study aimed to evaluate the safety and efficacy of the fixed-ratio combination (FRC) and free combination of basal insulin and glucagon-like peptide-1 receptor agonist (GLP-1RA) in patients with type 2 diabetes mellitus (T2DM)., Methods: PubMed, Web of Science, Embase, The Cochrane Library, and four Chinese databases were searched for relevant studies from inception to April 13, 2023. Phase III clinical trials involving FRC or free combination in patients with uncontrolled T2DM were included. A network meta-analysis (NMA) was used to evaluate the effects of FRC and free combination. The Cochrane Collaboration's tool was used to evaluate the risk-of-bias. The primary outcomes were changes in hemoglobin A1c (HbA1c), body weight, and incident hypoglycemia. Secondary outcomes included changes in systolic blood pressure (SBP) and diastolic blood pressure (DBP). This study was registered with PROSPERO (CRD42023409585)., Results: Forty-two trials with 23,619 patients were included in the NMA, and treatments were categorized as FRC, free combination and NOINSGLP (neither FRC nor free combination). The forest plots revealed comparable HbA1c control (mean difference (MD) = 0.07%, 95% confidence interval (CI): -0.17 to -0.30) between free combination and FRC. However, there were significant differences in the body weight (MD = -2.06 kg; 95% CI: -3.34 to -0.77), SBP (MD = -1.22 mmHg; 95% CI: -2.41 to -0.04), and DBP (MD = -1.09 mmHg; 95% CI: -1.94 to -0.24) between the two groups., Conclusions: In patients with uncontrolled T2DM, the safety and efficacy of FRC and free combination therapy were comparable. The use of FRC is justifiable in patients requiring free combination., (© 2024 Chinese Cochrane Center, West China Hospital of Sichuan University and John Wiley & Sons Australia, Ltd.)

Objective: To evaluate the association of insulin injection adherence, smart insulin pen engagement, and glycemic control using real-world data from 16 countries from adults self-administering basal insulin degludec and bolus insulin with a smart insulin pen (NovoPen 6 or NovoPen Echo Plus) alongside continuous glucose monitoring (CGM)., Research Design and Methods: Data were aggregated over 14-day periods. Treatment adherence was defined according to the number of missed basal and missed bolus insulin doses and smart pen engagement according to the number of days with data uploads., Results: Data from 3,945 adults, including 25,157 14-day periods with ≥70% CGM coverage, were analyzed. On average, 0.2 basal and 6.0 bolus insulin doses were missed over 14 days. The estimated probability of missing at least one basal insulin dose over a 14-day period was 17.6% (95% CI 16.5, 18.7). Missing one basal or bolus insulin dose per 14 days was associated with a significant decrease in percentage of time with glucose levels in range (TIR) (3.9-10.0 mmol/L), of -2.8% (95% CI -3.7, -1.8) and -1.7% (-1.8, -1.6), respectively; therefore, missing two basal or four bolus doses would decrease TIR by >5%. Smart pen engagement was associated positively with glycemic outcomes., Conclusions: This combined analysis of real-world smart pen and CGM data showed that missing two basal or four bolus insulin doses over a 14-day period would be associated with a clinically relevant decrease in TIR. Smart insulin pens provide valuable insights into treatment injection behaviors., (© 2024 by the American Diabetes Association.)

The objective of this review was to comprehensively present and summarize trends in reported rates of hypoglycemia with one or two times per day basal insulin analogs in individuals with type 2 diabetes to help address and contextualize the emerging theoretical concern of increased hypoglycemic risk with once-weekly basal insulins.Hypoglycemia data were extracted from treat-to-target randomized clinical trials conducted during 2000-2022. Published articles were identified on PubMed or within the US Food and Drug Administration submission documents. Overall, 57 articles were identified: 44 assessed hypoglycemic outcomes in participants receiving basal-only therapy (33 in insulin-naive participants; 11 in insulin-experienced participants), 4 in a mixed population (insulin-naive and insulin-experienced participants) and 9 in participants receiving basal-bolus therapy. For the analysis, emphasis was placed on level 2 (blood glucose <3.0 mmol/L (<54 mg/dL)) and level 3 (or severe) hypoglycemia.Overall, event rates for level 2 or level 3 hypoglycemia across most studies ranged from 0.06 to 7.10 events/person-year of exposure (PYE) for participants receiving a basal-only insulin regimen; the rate for basal-bolus regimens ranged from 2.4 to 13.6 events/PYE. Rates were generally lower with second-generation basal insulins (insulin degludec or insulin glargine U300) than with neutral protamine Hagedorn insulin or first-generation basal insulins (insulin detemir or insulin glargine U100). Subgroup categorization by sulfonylurea usage, end-of-treatment insulin dose or glycated hemoglobin reduction did not show consistent trends on overall hypoglycemia rates. Hypoglycemia rates reported so far for once-weekly basal insulins are consistent with or lower than those reported for daily-administered basal insulin analogs., Competing Interests: Competing interests: JR has served on advisory panels for Applied Therapeutics, Biomea Fusion, Boehringer Ingelheim, Eli Lilly, Endogenex, Hanmi, Novo Nordisk, Oramed, Regor, Sanofi, Scholar Rock, Structure Therapeutics, Terns Pharmaceuticals and Zealand Pharma; and has received research support, consulting fees or honoraria from Applied Therapeutics, AstraZeneca, Biomea Fusion, Boehringer Ingelheim, Eli Lilly, Endogenex, Hanmi, Novo Nordisk, Oramed, Regor, Sanofi, Scholar Rock, Structure Therapeutics, Terns Pharmaceuticals and Zealand Pharma. HSB reports trial fees paid to his institution by Amgen, AstraZeneca, Boehringer Ingelheim, Ceapro, Eli Lilly, Gilead, Janssen, Kowa Pharmaceuticals, Madrigal Pharmaceuticals, Merck, Novartis, Novo Nordisk, Pfizer, Sanofi, Ionis and Tricida. IL reports receiving grants, personal fees, or non-financial support from Sanofi, Lilly, Boehringer Ingelheim, Merck/Pfizer, Mylan, AstraZeneca, Johnson & Johnson, Intercept, Target Pharma, Zealand, Shionogi, Carmot, Structure, Bayer, Mediflix, WebMD, GI Dynamics, Intarcia Therapeutics, Mannkind, Novartis, Novo Nordisk, Structure Therapeutics and Valeritas. SRH reports consultancy with Eli Lilly, Zealand Pharma and Zucara Pharma; has participated in speaker panels for AstraZeneca, Medtronic and Novo Nordisk; and receives grant support from Dexcom., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Basal insulin continues to be a vital part of therapy for many people with diabetes. First attempts to prolong the duration of insulin formulations were through the development of suspensions that required homogenization prior to injection. These insulins, which required once- or twice-daily injections, introduced wide variations in insulin exposure contributing to unpredictable effects on glycemia. Advances over the last 2 decades have resulted in long-acting, soluble basal insulin analogues with prolonged and less variable pharmacokinetic exposure, improving their efficacy and safety, notably by reducing nocturnal hypoglycemia. However, adherence and persistence with once-daily basal insulin treatment remains low for many reasons including hypoglycemia concerns and treatment burden. A soluble basal insulin with a longer and flatter exposure profile could reduce pharmacodynamic variability, potentially reducing hypoglycemia, have similar efficacy to once-daily basal insulins, simplify dosing regimens, and improve treatment adherence. Insulin icodec (Novo Nordisk) and insulin efsitora alfa (basal insulin Fc [BIF], Eli Lilly and Company) are 2 such insulins designed for once-weekly administration, which have the potential to provide a further advance in basal insulin replacement. Icodec and efsitora phase 2 clinical trials, as well as data from the phase 3 icodec program indicate that once-weekly insulins provide comparable glycemic control to once-daily analogues, with a similar risk of hypoglycemia. This manuscript details the technology used in the development of once-weekly basal insulins. It highlights the clinical rationale and potential benefits of these weekly insulins while also discussing the limitations and challenges these molecules could pose in clinical practice., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society.)

Aim/introduction: Insulin glargine U100/lixisenatide and insulin degludec/liraglutide are fixed-ratio combinations containing basal insulin and a glucagon-like peptide-1 receptor agonist capable of reducing both fasting and postprandial blood glucose levels with a single formulation. This study aimed to compare the time in range (TIR) and the time below range (TBR) level 1 using professional continuous glucose monitoring and to establish criteria for the differential use of the fixed-ratio combinations., Materials and Methods: Thirty-six outpatients with type 2 diabetes mellitus (24 men and 12 women; average age, 62.1 years) were randomly assigned to the groups. At 0 and 18 weeks, a device was worn to compare the TIR and TBR level 1. The correlation between the C-peptide index at baseline and TIR at 18 weeks was assessed., Results: The TIR and TBR level 1 showed no significant differences between the two groups. Both groups showed significant positive correlations between the C-peptide index and the TIR (P = 0.002, r = 0.679; P = 0.002, r = 0.681, respectively). The changes in glycemic variability, therapeutic indices, and body mass index were not significantly different among the groups (P > 0.05). The receiver operating curve analysis revealed that the cut-off values of the C-peptide index to achieve TIR of >70% at 18 weeks were 1.258 (sensitivity, 77.8%; specificity, 100%) and 1.099 (sensitivity, 57.1%; specificity, 90.9%) in the insulin glargine U100/lixisenatide and insulin degludec/liraglutide groups, respectively., Conclusions: A TIR of >70% was achieved for both fixed-ratio combinations without significant differences., (© 2024 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.)

Background: Derived time in range (dTIR), calculated from self-monitored blood glucose (SMBG-dTIR) profiles, has demonstrated correlation with risk of cardiovascular and microvascular complications. This post hoc analysis of the DUAL V and DUAL VIII trials aimed to compare dTIR with an insulin degludec/liraglutide fixed-ratio combination (IDegLira) versus insulin glargine 100 units/mL (glargine U100) in people with type 2 diabetes (T2D)., Materials and Methods: Nine-point SMBG profiles were taken more than 24 hours at baseline and end of trial (EOT: 26 weeks [DUAL V] and 104 weeks [DUAL VIII]) and used to derive the percentage of readings within target range (70-180 mg/dL). Estimated treatment differences (ETDs, IDegLira-glargine U100) were analyzed using analysis of covariance, with treatment as fixed effects and baseline response as a covariate., Results: ETDs for change from baseline to EOT in dTIR were significantly greater with IDegLira versus glargine U100 in DUAL V (4.18%, P = .027) and DUAL VIII (5.17%, P = .001). The proportions of people achieving ≥70% dTIR at EOT with IDegLira and glargine U100, respectively, were 62% and 60% in DUAL V ( P = .7541), and 50% and 26% in DUAL VIII ( P < .0001). The proportion achieving a ≥5% increase in dTIR from baseline to EOT with IDegLira and glargine U100 was 63% in both groups in DUAL V ( P = .9043), and 44% and 25%, respectively, in DUAL VIII ( P < .0001)., Conclusions: IDegLira was associated with significantly greater increases in dTIR versus basal insulin alone in people with T2D., Trial Id(s): ClinicalTrials.gov, NCT01952145 (DUAL V); ClinicalTrials.gov, NCT02501161 (DUAL VIII)., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: AP-T provides consulting and research services to Novo Nordisk, Lilly, Bayer, Dexcom, and Medtronic on behalf of her employer but receives no direct or indirect reimbursement for the services. VRA reports consulting fees from Applied Therapeutics, Fractyl, Novo Nordisk, Pfizer, Sanofi, and institutional contracts for research from Applied Therapeutics/Medpace, Eli Lilly, Premier/Fractyl, Novo Nordisk, and Sanofi/Medpace. Her spouse is an employee of Janssen. CDB reports consulting fees and honoraria for speaking for Abbott, AstraZeneca, Boehringer-Ingelheim, Eli Lilly, Insulet, Medtronic, Novo Nordisk, and Roche. LKB reports honoraria for attending advisory boards or consulting services provided to Lilly, Novo Nordisk, Xeris, Bayer, and Sanofi. AL has received research support and honoraria for giving presentations and attending advisory boards: AstraZeneca, Bayer, Becton Dickinson, Boehringer-Ingelheim, Bristol Myers Squibb, Lilly, Medtronic, MSD, Novo Nordisk, Roche, and Sanofi. IL reports receiving advisory board fees and consulting fees from AstraZeneca, consulting fees from Bayer Healthcare Pharmaceuticals, Eli Lilly and Company, Intarcia, Intercept Pharmaceuticals, Janssen Global Services, MannKind Corporation, Target Pharma, Valeritas, and Zealand Pharma; advisory board fees from Boehringer-Ingelheim and Sanofi US Services; grant support, paid to UT Southwestern, from Merck; grant support, paid to her institution, from Mylan Pharmaceuticals and Pfizer; grant support, paid to UT Southwestern; and advisory board fees, consulting fees, and travel support from Novo Nordisk. RS and JMD’C are employees of Novo Nordisk A/S.

Objectives: The real-world ARISE study demonstrated initiation of fixed-ratio combination insulin degludec and aspart (IDegAsp) led to improvements in people achieving key glycemic control targets compared with prior therapies in Australia and India. This study evaluated the short-term cost-effectiveness of IDegAsp in these countries, in terms of the cost per patient achieving these targets., Methods: A model was developed to evaluate the cost of control (treatment costs divided by the proportion of patients achieving each target) of IDegAsp versus prior therapies received in ARISE for 2 endpoints: glycated hemoglobin (HbA1c) <7.0%, and HbA1c less than a predefined individual treatment target. Costs, expressed from a healthcare payer perspective, were captured in 2022 Australian dollars (AUD) and 2022 Indian rupees (INR)., Results: The number of patients needed to treat to bring one to endpoints of HbA1c <7.0% and less than an individualized target with IDegAsp was 51% and 87% lower, respectively, than with prior therapies in Australia, and 52% and 66% lower, respectively, versus prior therapies in India. Cost of control was AUD 2449 higher and AUD 64 863 lower with IDegAsp versus prior therapies for endpoints of HbA1c <7.0% and less than an individualized target, respectively, in Australia and INR 211 142 and INR 537 490 lower with IDegAsp compared with prior therapies in India., Conclusions: IDegAsp was estimated to be cost-effective versus prior therapies when considering an individualized HbA1c target in Australia, and when considering an individualized HbA1c target and HbA1c <7.0% in India., Competing Interests: Author Disclosures Author disclosure forms can be accessed in the Supplemental Material section., (Copyright © 2024 International Society for Health Economics and Outcomes Research. Published by Elsevier Inc. All rights reserved.)

Objective: There is a relative lack of consensus regarding the optimal management of hyperglycemia in patients receiving continuous enteral nutrition (EN), with or without a diagnosis of diabetes., Methods: This retrospective study examined 475 patients (303 with known diabetes) hospitalized in critical care setting units in 2019 in a single center who received continuous EN. Rates of hypoglycemia, hyperglycemia, and glucose levels within the target range (70-180 mg/dL) were compared between patients with and without diabetes, and among patients treated with intermediate-acting (IA) biphasic neutral protamine Hagedorn 70/30, long-acting (LA) insulin, or rapid-acting insulin only., Results: Among those with type 2 diabetes mellitus, IA and LA insulin regimens were associated with a significantly higher proportion of patient-days in the target glucose range and fewer hyperglycemic days. Level 1 (<70 mg/dL) and level 2 (<54 mg/dL) hypoglycemia occurred rarely, and there were no significant differences in level 2 hypoglycemia frequency across the different insulin regimens., Conclusion: Administration of IA and LA insulin can be safe and effective for those receiving insulin doses for EN-related hyperglycemia., Competing Interests: Disclosure The authors have no conflicts of interest to disclose., (Copyright © 2024 AACE. Published by Elsevier Inc. All rights reserved.)

Background: The efficacy and safety of fixed-ratio combination insulin degludec/liraglutide (IDegLira) for type 2 diabetes (T2DM) were extensively investigated by the global DUAL trials. However, the evidence on its efficacy and safety in T2DM has not been systematically reviewed., Methods: Randomized controlled trials published in English that compared IDegLira with placebo or GLP-1 agonists or insulin in patients with T2DM were selected up to December 2022. Data on the study characteristics, efficacy and safety outcomes were extracted. We compared the efficacy and safety between "IDegLira versus Insulin," "IDegLira versus GLP-1RA," and "IDegLira versus Placebo". The risk of potential bias was assessed., Results: In terms of glycaemic efficacy, IDegLira reduced levels of glycated haemoglobin (HbA1c; weighted mean differences (WMDs) 0.52%, 95% CI 0.33%-0.71%); fasting blood glucose (0.32 mg/dL, 0.14-0.50 mg/dL), and the nine-point self-measured plasma glucose (0.25 mmol/L, 0.25-0.36 mmol/L). Furthermore, IDegLira was generally better in the attainment of HbA1c < 7.0% or ≤6.5%, HbA1c < 7.0% or ≤6.5% without weight gain and/or without severe or blood glucose-confirmed hypoglycaemic episodes. In non-glycaemic efficacy aspects, IDegLira decreased systolic blood pressure but elevated heart rate. In terms of safety outcomes, IDegLira did not appear to be associated with a risk of hypoglycaemia (RR 1.23, 0.85-1.78) and nocturnal hypoglycaemia (0.89, 0.52-1.52) occurring when compared with other hypoglycaemic agents or placebo., Conclusions: IDegLira improves better glycaemic and non-glycaemic outcomes without weight gain and/or without severe or blood glucose-confirmed hypoglycaemic episodes in T2DM. Side effects of IDegLira are mild., (© 2023 John Wiley & Sons Ltd.)

Introduction: Insulin treatment is fundamental to diabetes management. Basal insulin therapy reduces intraday glycemic fluctuations upon reaching a steady state. Besides better blood glucose regulation and achieving target HbA1c values in patients, it also offers protection from diabetes complications. In this review, we aimed to compare basal-acting insulins in light of the literature., Areas Covered: We reviewed current evidence related to diabetes treatment with basal insulins. This includes discussions on clinical trials and meta-analyses concerning first and second-generation ultra-long-acting basal insulins. Treatment indications for long-acting basal insulins, which have shown benefits and are considered superior or comparable to others in the literature, are derived from current clinical studies and meta-analyses, which form the basis of the recommendations in this review., Expert Opinion: First and second-generation basal insulins do not show much superiority over each other in terms of blood glucose regulation and reaching the target HbA1c. However, second-generation basal insulins cause fewer hypoglycemic events. We recommend using the appropriate basal insulin in patient-based, individualized treatments. Basal insulin Icodec may become more widely used over time, owing to its association with less hypoglycemia and a reduction in the number of injections.

Since its first use just over a century ago, insulin treatment has evolved dramatically, such that the molecules are physiologic in nature, and treatment can now closely resemble the natural hormone response over 24 hours. Newer, longer-acting basal insulin analogs have provided insulin therapies with improved characteristics and, therefore, ease of use, and can readily be incorporated as part of routine treatment for type 2 diabetes (T2D), but evidence suggests that insulin remains underused in people with T2D. We review the barriers to initiation of basal insulin and the education needed to address these barriers, and we provide practical pointers, supported by evidence, for primary care physicians and advanced practice providers to facilitate timely initiation of basal insulin in the people with T2D who will benefit from such treatment.

Objective: 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 rapidacting 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 the baseline, there was a significant improvement in glycated hemoglobin at the end of the study (EOS) (estimated difference [ED] -1.4% [95% confidence interval -1.7, -1.1]; P <0.0001). Fasting plasma glucose (ED -46.1 mg/dL [-58.2, -34.0]; P <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., Conclusion: 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., Competing Interests: Nicole-Therese Flor, Mercerose Puno-Rocamora, and Ahsan Shoeb are employees of Novo Nordisk Philippines, Taguig City, Philippines and hold stocks in Novo Nordisk., (© 2024 Journal of the ASEAN Federation of Endocrine Societies.)