Basal Insulin Research Articles

Use of Sliding Scale Insulin: Investigating the use of sliding scale insulin (SSI) in managing hyperglycemia in emergency cases in the hospital, and comparing it with evidence-based approaches like basal-bolus insulin regimens

Objective: This clinical audit focuses on identifying and describing the pattern of Sliding Scale Insulin in the management of hyperglycemia in emergencies in Lady Reading Hospital, Peshawar. This study matches SSI to EB-BBI to determine which of the two produces more favorable patient outcomes such as glycaemic control, incidence of hypoglycaemia, hospital stay, and mortality. Pre-intervention and post-intervention were audited to determine the best practice to embrace after the cycling accord. Methods: A total of 456 patients who developed hyperglycemia during their admission were part of the audit. A pilot survey during the first audit cycle (from 1 Dec 2023 to 29 Feb 2024) assessed the implementation of SSI versus basal-bolus insulin regimens. After applying the intervention strategies to enhance the use of basal-bolus insulin among the patients a second audit (from March 1 2024 to June 15, 2024) was conducted. Information from patient characteristics such as age, sex, insulin treatment and dose, glycemic control measures, complications, hospitalization length and mortality rate of patients were gathered and analyzed between the two cycles. Results: In the first audit cycle, 68% of patients were managed with SSI to increased risk of hypoglycemia 28% and longer hospital stay of 6.2 days compared to patients with basal bolus insulin who experienced 12% of hypoglycemia and 4.5 days of hospital stay. Interventions were used to decrease the use of SSI down to 45 %; this was accompanied by better results; for instance, incidences of hypoglycaemia were recorded at 19 % while the average length of stay in hospital was 5.4 days. The results in basal-bolus insulin regimens were more favorable, though all compared regimens had similar or slightly reduced mortality rates. Conclusion: The audit showed that basal-bolus insulin management regimens provided better and superior glycemic control and better patient outcomes than SSI in emergency hyperglycemia situations. In the first instance, implementing basal-bolus insulin posed lessons in staff development and had limited sources; nonetheless, the study established enhanced patient safety and shortened length of stay. Specifically, this audit assists to validate basal-bolus regimens as the best approach of treating hyperglycemia in emergencies.

Identifying the Relationship Between CGM Time in Range and Basal Insulin Adherence in People With Type 2 Diabetes.

The study aimed to determine the relationship between basal insulin adherence and glycemic control evaluated by time in range (TIR) in people with insulin-treated type 2 diabetes (T2D), using data from both continuous glucose monitors (CGM) and connected insulin pens. Furthermore, the study aimed to determine the best basal insulin adherence metric. CGM data and basal insulin data were collected from 106 insulin-treated people (aged ≥18 years) with T2D. Three different adherence metrics were employed (dose deviation, dose deviation ≤20%, and a traditional metric) and a three-step methodology was used to measure insulin adherence level. The coefficient of determination (R2), based on a univariate linear regression analysis, was used to determine the relationship between each adherence metric and TIR. A statistically significant relationship was observed between TIR and adherence quantified as the dose deviation ≤20% metric (R2 = 0.67, P = .006). Neither the relationship between the dose deviation metric and TIR (R2 = 0.43, P = .08) nor the relationship between the traditional metric and TIR (R2 = 0.35, P =.23) was found to be statistically significant. Our study indicates a relationship between basal insulin adherence and TIR in people with insulin-treated T2D. This seems to underscore the role of basal insulin adherence for optimal glycemic outcomes and utilizing TIR as a clinical marker. Furthermore, the results suggest that the magnitude of deviation from the recommended basal insulin dose impacts glycemic control, indicating dose deviation ≤20% as a more accurate metric for quantifying adherence.

Effect of Interrupting Prolonged Sitting with Frequent Activity Breaks on Postprandial Glycemia and Insulin Sensitivity in Adults with Type 1 Diabetes on Continuous Subcutaneous Insulin Infusion Therapy: A Randomized Crossover Pilot Trial.

Objective: This study examined acute effects of interrupting prolonged sitting with short activity breaks on postprandial glucose/insulin responses and estimations of insulin sensitivity in adults with type 1 diabetes (T1D). Method: In a randomized crossover trial, eight adults (age = 46 ± 14 years [mean ± SD], body mass index [BMI] = 27.2 ± 3.8 kg/m2) receiving continuous subcutaneous insulin infusion (CSII) therapy completed two 6-h conditions as follows: uninterrupted sitting (SIT) and sitting interrupted with 3-min bouts of simple resistance activities (SRAs) every 30 min. Basal and bolus insulin were standardized across conditions except in cases of hypoglycemia. Postprandial responses were assessed using incremental area-under-the-curve (iAUC) and total AUC (tAUC) from half-hourly venous sampling. Meal-based insulin sensitivity determined from glucose sensor and insulin pump (SiSP) was assessed from flash continuous glucose monitor and insulin pump data. Outcomes were analyzed using mixed models adjusted for sex, BMI, treatment order, and preprandial values. Results: Glucose iAUC did not differ by condition (SIT: 19.8 ± 3.0 [estimated marginal means ± standard error] vs. SRA: 14.4 ± 3.0 mmol.6 h.L-1; P = 0.086). Despite CSII being standardized between conditions, insulin iAUC was higher in SRA compared to SIT (137.1 ± 22.7 vs. 170.9 ± 22.7 mU.6 h.L-1; P < 0.001). This resulted in a lower glucose response relative to the change in plasma insulin in SRA (tAUCglu/tAUCins: 0.32 ± 0.02 vs. 0.40 ± 0.02 mmol.mU-1; P = 0.03). SiSP was also higher at dinner following the SRA condition, with no between-condition differences at breakfast or lunch. Conclusion: Regularly interrupting prolonged sitting in T1D may increase plasma insulin and improve insulin sensitivity when meals and CSII are standardized. Future studies should explore underlying mechanistic determinants and the applicability of findings to those on multiple daily injections. Trial Registration: Australian and New Zealand Clinical Trial Registry Identifier-ACTRN12618000126213 (www.anzctr.org.au).

The effect of small increases in blood glucose on insulin secretion and endogenous glucose production in humans.

Small glycemic increments (≤0.5 mmol/L) can exert suppressive actions on endogenous glucose production (EGP) however it is unclear if this is an insulin dependent or independent process. Here, we performed a low-rate glucose infusion in control participants without diabetes and in people with type 1 diabetes (T1D) to better understand this phenomenon. Glucose kinetics, hormones and metabolites were measured during a 1 mg/kg/min glucose infusion (90 min) which rapidly increased glucose by ∼0.3 mmol/L in control participants. Insulin concentrations and secretion quickly increased by ∼20%, resulting in a ∼40% suppression of EGP, while glucose disposal remained unchanged. Free fatty acids (FFA) and glucagon were gradually suppressed to ∼30% below baseline at 60 min. When repeated under constant basal insulin concentrations in participants with T1D, glucose infusion caused only partial and transient EGP suppression, hence glucose increased in a near-linear manner, reaching levels ∼2 mmol/L above baseline at 90 min. FFAs and glucagon remained unchanged, while glucose disposal modestly increased. This demonstrates that small glycemic increments exert subtle stimulatory effects on insulin secretion that have potent metabolic actions on the liver and adipose tissue. It is conceivable that subtle increases in glucose could potentially serve as a signal for β-cell adaptation.

Pharmacokinetic Properties of a Once-Weekly Fixed-Ratio Combination of Insulin Icodec and Semaglutide Compared with Separate Administration of Each Component in Individuals with Type 2 Diabetes Mellitus.

IcoSema is being developed as a subcutaneous once-weekly fixed-ratio combination of the once-weekly basal insulin icodec and the once-weekly glucagon-like peptide-1 receptor agonist semaglutide. This study investigated the pharmacokinetics of icodec and semaglutide in IcoSema versus separate administration of each component in individuals with type 2 diabetes mellitus (T2DM). In a randomised, double-blind, three-period crossover study, 31 individuals with T2DM (18-64 years, body weight 80-120 kg, glycosylated haemoglobin 6.0-8.5%) received single subcutaneous injections of IcoSema (175 U icodec, 0.5 mg semaglutide), icodec (175 U) or semaglutide (0.5 mg) with 6-9 weeks' washout. Pharmacokinetic blood samples were drawn up to 840 h post-dose. Icodec pharmacokinetics were unaffected by combining icodec with semaglutide. The 90% confidence interval (CI) of IcoSema/icodec was within 0.80-1.25 for total exposure (area under the curve from zero to last quantifiable observation; AUC0-t: ratio [90% CI] 1.06 [1.01; 1.12]) and maximum concentration (Cmax): 1.12 [1.06; 1.18]. Semaglutide AUC0-t was also unaffected by combination with icodec (IcoSema/semaglutide 1.11 [1.05; 1.17]). However, semaglutide Cmax was higher for IcoSema versus semaglutide alone (IcoSema/semaglutide 1.99 [1.84; 2.15]) and occurred earlier for IcoSema (12 versus 84 h). Results of in vitro albumin binding studies and animal pharmacokinetic studies supported that the change in semaglutide absorption pharmacokinetics in IcoSema is owing to competition for albumin binding locally at the injection site with icodec outcompeting semaglutide. IcoSema, icodec and semaglutide were well-tolerated, although more gastrointestinal related adverse events occurred with IcoSema versus icodec or semaglutide alone. The combination of icodec and semaglutide in IcoSema leads to a higher and earlier maximum semaglutide concentration, which will guide the dose recommendations for IcoSema. ClinicalTrials.gov identifier: NCT03789578.

Treatment Patterns and Glycaemic Control Between 2015 and 2019 in Tianjin, China: A Real-World Study of Adults with Type 2 Diabetes.

Diabetes is associated with a high economic burden in China; therefore, strategies to prevent diabetes, improve glycaemic control, delay disease-related complications and maintain quality of life are essential. This study was conducted to evaluate trends in treatment patterns and glycaemic control in people with type 2 diabetes (T2D) in real-world clinical practice in Tianjin, China. This retrospective, cross-sectional, multicentre study analysed data from adults with T2D living in Tianjin, China between 2015 and 2019, based on information obtained from a regional electronic medical record database. Temporal trends in treatment patterns and glycaemic control were assessed using linear regression (continuous variables), and Cochran-Armitage (two categories) or Cochran-Mantel-Haenszel (≥ 3 categories) tests. Between 2015 and 2019, data from 312,203 individuals treated at 75 hospitals were included. Over this period, there was an upward trend in the prevalence of hypertension, hyperlipidaemia, obesity, cardiovascular disease, stroke and retinopathy each year (all P < 0.001). The use of metformin or dipeptidyl peptidase-4 inhibitors increased, while thiazolidinedione, alpha-glucosidase inhibitor and glinide use decreased; the use of basal insulin (BI), glucagon-like peptide-1 receptor agonists (GLP-1 RAs), GLP-1 RAs + BI, bolus insulin and BI + bolus insulin increased, whereas the use of premixed insulin showed a downward trend (all P < 0.001). From 2015 to 2019, an increased proportion of individuals achieved glycated haemoglobin (HbA1c) < 7% (< 53 mmol/mol; 28.1-33.7%), fasting plasma glucose (FPG) < 7 mmol/l (21.7-26.9%) and postprandial glucose (PPG) < 10 mmol/l (22.0-48.2%; all P < 0.001). There was no change in the proportion of individuals with an FPG ≥ 7 mmol/l and a PPG ≥ 10 mmol/l, while the prevalence of residual hyperglycaemia increased (P < 0.001). Glycaemic control improved between 2015 and 2019 in people with T2D in Tianjin, China; however, there is an unmet need for more effective glycaemic control.

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.

Use of Glucagon-like Peptide 1 Receptor Agonist to Sustain Patients off Basal-Bolus Insulin Regimens

BackgroundThe 2024 Standards of Care in Diabetes recommend initiation of glucagon-like peptide 1 receptor agonists (GLP-1 RAs) prior to starting basal insulin and to reconsider initiating a GLP-1 RA before starting bolus insulin if not already initiated. GLP-1 RA addition leads to improved glycemic benefits as well as risk reduction of cardiovascular and renal outcomes in patients with a history of these events. While there is evidence demonstrating the trends of insulin reduction or discontinuation following GLP-1 RA initiation, data regarding longer-term durability of GLP-1 RA use to sustain patients off bolus insulin is lacking. ObjectiveThis retrospective study aimed to assess the percentage of patients remaining off bolus insulin after transitioning from a basal-bolus regimen to GLP-1 RA therapy with basal insulin over a period of three years. MethodsWe conducted a single centered, retrospective study analyzing patient data from July 2018 through July 2023. Patients were included if they had a diagnosis of type 2 diabetes, were on a basal-bolus insulin regimen, had a GLP-1 RA initiated followed by bolus insulin discontinuation within 90 days, and remained on a GLP-1 RA for at least six months. The primary outcome was the percentage of patients who were sustained off bolus insulin after three years following GLP-1 RA initiation. ResultsThere were 252 patients included. At three years, 82.6% of patients were sustained off bolus insulin. The mean change in weight at three years was -8.5 kg. The mean A1c initially decreased from 8.6% to 7.8%, but then increased slightly to 8.1% at the end of the study timeframe. ConclusionThis trial demonstrated the majority of patients on basal-bolus regimens where bolus insulin was replaced with a GLP-1 RA were sustained off bolus insulin for a three year period of time. These results highlight the promising durability of converting bolus insulin to GLP-1 RAs.

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.

Exogenous insulin does not reduce protein catabolism in pre-diabetic cystic fibrosis patients: A randomized clinical trial

BackgroundCystic Fibrosis (CF) patients historically suffered from undernutrition, infection and inflammation. Insulin insufficiency-related protein catabolism further compromised health. We aimed to determine whether insulin improves protein catabolism in CF youth with abnormal glucose tolerance (AGT). MethodsThis double-masked, placebo-controlled trial in CF youth age 10–25 with AGT who were in their usual state of health used triple-tracer stable-isotope methodology to measure protein turnover during a baseline test meal and after four weeks of insulin/placebo treatment. Healthy controls were assessed once. CF patients were randomized 1:1:1 to once-daily long-acting insulin (0.25 U/kg/d), three-times daily rapid-acting insulin (0.5 U/15gr carbohydrate), or injectable placebo. ResultsThirty CF patients completed the study. There were no differences in any measure of protein turnover between insulin- and placebo-treated subjects, including endogenous protein breakdown (primary study endpoint). In contrast to earlier studies, protein turnover in the 37 CF patients who completed the baseline meal was normal compared to 20 healthy controls. Meal isotope appeared in plasma earlier in CF than controls, suggesting more rapid gut emptying. The study was interrupted by the pandemic; futility analysis led to study discontinuation before the planned remaining 15 CF patients were studied. ConclusionsRecent advances in CF have led to remarkable clinical improvements. In this study, CF youth with AGT had normal protein catabolism at baseline. Pre-meal or daily basal insulin therapy, while safe and well tolerated, did not significantly enhance protein turnover and does not appear to be necessary in clinically stable patients prior to development of CFRD.

Real world effectiveness of oral semaglutide: Focus on patients with type 2 diabetes older than 75 years

AimData on the efficacy of oral semaglutide (OS) in elderly patients with type 2 diabetes are still lacking. This study evaluates the effectiveness of OS in a real world setting with a large ≥75 year old population. MethodsThis study includes all type 2 diabetic patients who started OS between October 2021 and December 2023 in seven diabetes centers. Data were collected at baseline, 6 (T6) and 12 (T12) months. Effectiveness measures were assessed on the total sample and by patient age (<65, 65–75, >75 years). ResultsOverall 1824 patients started OS, of those 18.7 % were over 75 years (>75 yr). OS resulted in a significant reduction in rate of patients using sulphonylureas, rapid and basal insulin therapy, HbA1c reduced by 0.87 % at T6 and at T12 (both p < 0.0001), body weight by 2.78 Kg (p < 0.0001) at T6 and 3.89 Kg (p < 0.0001) at T12. Similarly, >75 yr showed HbA1c reduction at T6 (p < 0.0001) and T12 (p = 0.0003), body weight significantly reduced (p for interaction 0.005) both at T6 (−1.57 Kg; p = 0.0003) and T12 (−2.74 Kg; p < 0.0001). ConclusionIn our study, OS results efficacy in non-elderly and elderly patients, making it an effective treatment option also for very elderly type 2 diabetic patients.

Cost-utility analysis of once-weekly insulin icodec and once-daily insulin glargine in patients with type 2 diabetes receiving basal-bolus insulin therapy in China.

The purpose of this study is to explore the rational pricing range for the once-weekly administration of insulin icodec in the treatment of type 2 diabetes patients in China who have already received basal insulin therapy. The data foundation of this study originates from the ONWARDS 4 clinical trial and research materials on Chinese type 2 diabetes patients. By comprehensively applying cost-utility analysis methods and binary search techniques, the appropriate price positioning of insulin icodec was determined from the perspective of China's healthcare system. In the long-term treatment simulation, we found that insulin icodec and insulin glargine performed similarly in terms of quality-adjusted life years (QALYs), with 10.15 and 10.07 years, respectively. Although the annual cost of insulin icodec was initially assumed to be equivalent to that of insulin glargine, in-depth analysis revealed that insulin icodec may have higher cost-effectiveness potential. Further price sensitivity analysis indicated that the reasonable cost range of insulin icodec lies between $851.95 and $1358.25. After fine-tuning through univariate sensitivity analysis, this cost range was revised to $784.90 to $1145.96, a conclusion that was robustly validated in subsequent probabilistic sensitivity analysis and scenario simulations. The conclusion drawn from this study is that, with insulin glargine as the cost reference, the economic cost of insulin icodec for Chinese type 2 diabetes patients is expected to range from $784.90 to $1145.96, providing a reference basis for clinical decision-making and healthcare policy formulation.

Effectiveness and Safety of GLP-1 Receptor Agonists in Patients with Type 1 Diabetes.

Background: GLP-1 receptor agonists (GLP-1RA) are used in the management of type II diabetes mellitus or obesity, although its role in patients with type I diabetes mellitus (T1DM) has been debated. This study aimed to investigate the efficacy and safety of GLP-1RA in patients with T1DM using real-world data. Methods: This multicenter, retrospective study was conducted at three tertiary medical centers in Riyadh, Saudi Arabia. The study followed up patients (>16 years old) with T1DM treated with insulin followed by GLP-1RA add-on therapy. The efficacy outcomes included changes in HbA1c, body weight, and insulin requirements from baseline to each follow-up visit. The main safety outcomes assessed included hypoglycemic events and gastrointestinal (GI) adverse events. Results: The study included 144 patients with a mean age of 33.0 ± 10.1 years. Semaglutide was the most used GLP-1RA (63.9%) followed by liraglutide (34.0%). From baseline to 3-month follow-up, HbA1c (mean difference (MD) = -0.8%; p = 0.0053), weight (MD = -2.4 kg; p = 0.0253), and daily basal insulin dose (MD = -2.1 units; p = 0.0349) were significantly reduced. Likewise, HbA1c (MD = -0.5%; p = 0.0004), weight (MD = -3.6 kg; p < 0.0001), and daily basal insulin (MD = -2.4 units; p = 0.0282) were significantly reduced at the 4-6-month follow-up. The significant reductions in HbA1c, weight, and daily basal insulin levels were consistent for up to 18-month follow-up. Only one patient had a major hypoglycemic event, whereas 8.3% of the patients had GI adverse events. Conclusions: Overall, significant improvements in glycemic control, weight loss, and insulin requirements were observed with the use of GLP-1RA in patients with T1DM, with a limited number of GI adverse events.

A real-world data analysis investigating the cardioprotective effects of glucagon-like peptide-1 receptor agonists among people with type 2 diabetes in England

Abstract Background Cardiovascular disease (CVD) is a common and major complication of type 2 diabetes (T2D). Anti-diabetic therapy aims to lower blood glucose, with primary clinical trial endpoints for new antidiabetic entrants focused on HbA1c. Research suggests some glucose-lowering drugs, including glucagon-like peptide-1 receptor agonists (GLP-1 RAs), can have a cardioprotective effect in people with T2D.1,2 Purpose To compare the real-world risk of major adverse cardiovascular event (MACE) in people with T2D treated with GLP-1 RAs compared to dipeptidyl peptidase-4 (DPP-4) inhibitors or basal insulin. Methods We conducted a retrospective cohort study using linked primary care data from the Clinical Practice Research Datalink Aurum, secondary care Hospital Episode Statistics and Office for National Statistics death registrations. We included patients aged ≥18 years with T2D at high-risk or very-high-risk of CVD (as defined by the European Society of Cardiology) who had ≥2 prescriptions of either GLP-1 RA (dulaglutide, liraglutide, and semaglutide), DPP-4 inhibitor (as part of line 4 therapy) or basal insulin from 01/01/2014-31/12/2018. We excluded those pregnant at therapy initiation or with type 1 diabetes. Follow-up started at second prescription of relevant therapy and ended at the earliest of two years later, pregnancy, death, end of primary care record, or 31/12/2019. We used data from patients’ medical histories to define baseline characteristics. We calculated the incidence of MACE per 100,000 person-years (PY), defined as non-fatal myocardial infarction, non-fatal stroke, and cardiovascular death. We used Cox proportional hazards regression, using LASSO to select confounding clinical variables including BMI, prior MACE and intercurrent antidiabetic treatments, to estimate risk difference of MACE among those treated with 1) GLP1-RA and DPP-4 inhibitor and 2) GLP1-RA and basal insulin. Results We included 63,237 patients, among whom the patients treated with GLP1-RA were younger and a higher proportion were obese or severely obese than those treated with DPP-4 inhibitor or basal insulin (Table 1). The incidence of MACE was highest in those treated with DPP-4 inhibitor (high-risk 1,503.0/100,000 PY; very-high-risk 6,000.7/100,000 PY) followed by basal insulin (high-risk 1,396.9/100,000 PY; very-high-risk 5,707.1/100,000 PY), and lowest in those treated with GLP1-RA (high-risk 377.1/100,000 PY; very-high-risk 1,946.1/100,000 PY). After adjustment, the risk of MACE among patients treated with GLP1-RA was still significantly lower than those treated with either DPP-4 inhibitor (high-risk aHR: 0.42, 95% CI 0.21-0.86 and very-high-risk aHR: 0.65, 95% CI 0.58-0.73) or those treated with basal insulin (high-risk aHR: 0.36, 95% CI 0.18-0.72 and very-high-risk aHR: 0.72, 95% CI 0.64-0.81). Conclusion(s) Our study supports clinical trial and other observational research studies which find a cardioprotective effect of GLP-1 RA use in people with T2D.

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.

Intermittently scanned continuous glucosemonitoring compared with blood glucose monitoring is associated with lower HbA1c and a reduced risk of hospitalisation for diabetes-related complications in adults with type 2 diabetes on insulin therapies.

We assessed the impact of initiating intermittently scanned continuous glucose monitoring (isCGM) compared with capillary blood glucose monitoring (BGM) on HbA1c levels and hospitalisations for diabetes-related complications in adults with insulin-treated type 2 diabetes in Sweden. This retrospective comparative cohort study included adults with type 2 diabetes who had a National Diabetes Register initiation date for isCGM after 1 June 2017. Prescribed Drug Register records identified subgroups treated with multiple daily insulin injections (T2D-MDI) or basal insulin (T2D-B), with or without other glucose-lowering drugs. The National Patient Register provided data on hospitalisation rates. We identified 2876 adults in the T2D-MDI group and 2292 in the T2D-B group with an isCGM index date after 1 June 2017, matched with 33,584 and 43,424 BGM control participants, respectively. The baseline-adjusted difference in the change in mean HbA1c for isCGM users vs BGM control participants in the T2D-MDI cohort was -3.7 mmol/mol (-0.34%) at 6 months, and this was maintained at 24 months. The baseline-adjusted difference in the change in HbA1c for isCGM users vs BGM control participants in the T2D-B cohort was -3.5 mmol/mol (-0.32%) at 6 months, and this was also maintained at 24 months. Compared with BGM control participants, isCGM users in the T2D-MDI cohort had a significantly lower RR of admission for severe hypoglycaemia (0.51; 95% CI 0.27, 0.95), stroke (0.54; 95% CI 0.39, 0.73), acute non-fatal myocardial infarction (0.75; 95% CI 0.57, 0.99) or hospitalisation for any reason (0.84; 95% CI 0.77, 0.90). isCGM users in the T2D-B cohort had a lower RR of admission for heart failure (0.63; 95% CI 0.46, 0.87) or hospitalisation for any reason (0.76; 95% CI 0.69, 0.84). This study shows that Swedish adults with type 2 diabetes on insulin who are using isCGM have a significantly reduced HbA1c and fewer hospital admissions for diabetes-related complications compared with BGM control participants.

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.

Icodec ONWARDS: A review of the first once-weekly diabetes treatment for nurse practitioners and physician assistants.

Diabetes management is challenged by the complexity of treatment regimens and the need for frequent injections, affecting patient adherence and quality of life. Insulin icodec, a once-weekly basal insulin analog, represents a significant innovation, potentially simplifying diabetes care and improving outcomes. This review aims to evaluate the safety, efficacy, and clinical implications of insulin icodec for individuals with type 1 and type 2 diabetes, highlighting its potential to affect current treatment paradigms. A review was conducted comparing once-weekly insulin icodec with daily basal insulin analogs using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines to ensure transparent reporting of systematic reviews. A search was performed in the following databases: PubMed, Google Scholar, Embase, and ClinicalTrials.gov, focusing on efficacy and safety outcomes. Insulin icodec has demonstrated effective glycemic management and a safety profile comparable to daily basal insulins. Its extended half-life and steady-state glucose-lowering effect have the potential to reduce the burden of daily injections and improve patient adherence. The introduction of once-weekly insulin icodec represents an advancement in diabetes care. For front-line clinicians, this innovation aligns with the need for more straightforward medication regimens. Coupled with continuous glucose monitoring systems, it enables a more personalized and efficient approach to diabetes management, with the potential to improve patient satisfaction and clinical outcomes. This underscores the impact of integrating such advancements into practice, highlighting the role of nurse practitioners and physician assistants in adopting these innovations to optimize patient care.

The impact of vitamin D3 administration and of high fat diet on oxidative stress and inflammation in experimentally induced polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is commonly associated with obesity and may be exacerbated by the lack of vitamin D3. The study aimed to investigate the effects of vitamin D3 administration in female rats with PCOS and prolonged high fat diet (HFD). Forty-four female Wistar rats, 180-200 g, 10 weeks old, were randomly allocated into 2 groups (n=22) that received a single dose intramuscular injection of: sesame oil (group I), or estradiol valerate (5 mg) in sesame oil (group II). After 4 weeks, intraovarian cysts developed in group II, as evidenced by ultrasonography. In the next step, half of rats from each group received standard diet (SD) and the other half high fat diet, through oral gavage, for 17 weeks, the following groups being obtained: Control (SD), HFD, PCOS (PCOS+SD) and PCOS+HFD. Next, all the rats received, for 5 weeks, 500 UI/kg/day vitamin D3, through oral gavage. Lipid peroxidation was assessed through malondialdehyde level in the ovary and periovarian tissue and the inflammation was quantified in ovary by NFkB, pNFkB, NRF2 and SOD1 expressions. Ovaries from all groups were collected for histopathological analysis. Blood samples were taken to evaluate the basal insulin, triglycerides and total cholesterol levels throughout the experiment. Both groups with PCOS recorded significant increases of malondialdehyde in ovaries (p<0.001) and in periovarian tissue, especially in PCOS+HFD (p<0.05), even after vitamin D3 administration. PCOS+HFD group treated with vitamin D3 showed a high degree of inflammation in ovarian histopathology but with decreased pNFkB expression (p<0.01) while PCOS group recorded an increased SOD1 expression (p<0.05). Additionally, vitamin D3 treatment attenuated the insulin level (p<0.001) in PCOS and in HFD groups and the total cholesterol level in PCOS+HFD group, but triglycerides recordings were without statistical significance (p>0.05). HFD induced inflammation in ovaries, evidenced histologically and through increases of COX2 expressions (p<0.05) without significant influences on oxidative stress and on cholesterol levels. Polycystic ovary syndrome is associated with oxidative stress and inflammation in the ovary tissue and in blood with increased levels of insulin, total cholesterol and triglycerides that might be partially mitigated by vitamin D3 oral administration.

Chronic late gestation fetal hyperglucagonaemia results in lower insulin secretion, pancreatic mass, islet area and beta- and α-cell proliferation.

Fetal glucagon concentrations are elevated in the presence of a compromised intrauterine environment, as in cases of placental insufficiency and perinatal acidaemia. Our objective was to investigate the impact of late gestation fetal hyperglucagonaemia on in vivo insulin secretion and pancreatic islet structure. Chronically catheterized late gestation fetal sheep received an intravenous infusion of glucagon at low (5ng/kg/min; GCG-5) or high (50ng/kg/min; GCG-50) concentrations or a vehicle control (CON) for 8-10days.Glucose-stimulated fetal insulin secretion (GSIS) was measured following 3h (acute response) and 8-10days (chronic response) of experimental infusions. Insulin, glucose and amino acid concentrations were measured longitudinally. The pancreas was collected at the study end for histology and gene expression analysis. Acute exposure (3h) to GCG-50 induced a 3-fold increase in basal insulin concentrations with greater GSIS. Meanwhile, chronic exposure to both GCG-5 and GCG-50 decreased basal insulin concentrations 2-fold by day 8-10. Chronic GCG-50 also blunted GSIS at the study end. Fetal amino acid concentrations were decreased within 24h of GCG-5 and GCG-50, while there were no differences in fetal glucose. Histologically, GCG-5 and GCG-50 had lower β- and α-cell proliferation, as well as lower α-cell mass and pancreas weight, while GCG-50 had lower islet area. This study demonstrates that chronic glucagon elevation in late gestation fetuses impairs β-cell proliferation and insulin secretion, which has the potential to contribute to later-life diabetes risk. We speculate that the action of glucagon in lower circulating fetal amino acid concentrations may have a suppressive effect on insulin secretion. KEY POINTS: We have previously demonstrated in a chronically catheterized fetal sheep model that experimentally elevated glucagon in the fetus impairs placental function, reduces fetal protein accretion and lowers fetal weight. In the present study, we further characterized the effects of elevated fetal glucagon on fetal physiology with a focus on pancreatic development and β-cell function. We show that experimentally elevated fetal glucagon results in lower β- and α-cell proliferation, as well as decreased insulin secretion after 8-10days of glucagon infusion. These results have important implications for β-cell reserve and later-life predisposition to diabetes.