Rapid-acting Insulin Analogues Research Articles

Investigation of Severe Hypoglycemia Risk Among Patients with Diabetes Treated with Ultra-Rapid Lispro in Japan.

There is no information on the incidence of severe hypoglycemia in real-world patients with diabetes receiving ultra-rapid lispro (URLi). This post-marketing, observational, safety study assessed the incidence proportion and incidence rate of the first severe hypoglycemia event requiring a hospital visit in URLi-treated patients. It also compared the risk of severe hypoglycemia between patients treated with URLi or other rapid-acting insulin analogs (RAIAs). Claims data were obtained from a nationwide hospital-based administrative database in Japan (Medical Data Vision). Adults with diabetes who initiated URLi or other RAIA on/after June 01, 2020, were followed up through May 31, 2023. Severe hypoglycemia was identified using a validated algorithm. Incidence proportion and incidence rate of the first severe hypoglycemia event requiring a hospital visit was described in URLi-treated patients (descriptive analysis). These outcomes were also compared against propensity score (PS)-matched other RAIA-treated patients (comparator; comparative analysis). Hazard ratio (HR) and 95% confidence interval (CI) was estimated with a Cox proportional hazards model. The descriptive analysis' URLi-treated cohort included 17,838 patients [mean (standard deviation, SD) age 65.9 (15.7) years; 58.3% male]. The majority had type 2 diabetes (75.7%). The incidence proportion of the first severe hypoglycemia event requiring a hospital visit was 0.6% (95% CI 0.5, 0.8) and the incidence rate was 1.7 per 100 person-years (95% CI 0.7, 4.3). The comparative analysis included 10,592 URLi-treated and 52,917 comparator-treated patients. The incidence rate of severe hypoglycemia did not significantly differ between these cohorts (HR 0.8; 95% CI 0.5, 1.1; p=0.132;. This study did not show a statistically significant increase in the incidence and risk of the first severe hypoglycemia event requiring a hospital visit in real-world URLi-treated patients in Japan, compared with a PS-matched cohort of other RAIA-treated patients.

Safety Profiles Related to Dosing Errors of Rapid-Acting Insulin Analogs: A Comparative Analysis Using the EudraVigilance Database.

Diabetes is a widespread condition that can lead to multiple and severe complications. Rapid-acting insulin analogs (RAIAs) and long-acting insulin analogs are prescribed for the effective management of diabetes. RAIAs are expected to be associated with a higher number of dosing errors because of their rapid onset, short duration of action, and the need for frequent dosing, compared to other insulin analogs. There are three approved RAIAs on the market: insulin lispro (LIS), insulin aspart (ASP), and insulin glulisine (GLU). The aim of this study is to evaluate the real-world evidence on dosing errors reported for RAIAs in EudraVigilance (EV), an established pharmacovigilance database, in comparison to other insulin analogs and human insulins. A descriptive analysis and a disproportionality analysis were conducted. ASP and LIS were associated with high percentages of adverse drug reactions (ADRs) (22% and 17%, respectively), with over 70% of the reports involving serious ADRs. A higher frequency of cardiac and eye disorder ADRs was observed for LIS compared with ASP and GLU. GLU showed a higher frequency of ADRs in the skin and subcutaneous tissue disorders category. LIS dosing errors accounted for 5% of the total number of cases, while dosing errors for ASP and GLU were less than 3%. The most frequently reported dosing errors involved improper dosing (49%). Although there were fewer dosing errors of RAIAs in comparison to other insulins, the severity of the potential outcome highlights the importance of precise dosing and timing. Improved the monitoring and reporting of these dosing errors could enhance diabetes patient care. Additionally, smart medical devices could improve therapeutic outcomes.

A Position Statement on Diabetes with β-Cell Failure

Diabetes mellitus is a heterogeneous disease that encompasses a wide range of conditions, from mild cases to severe conditions where survival depends on insulin therapy. The Korean Diabetes Association Task Force Team for Diabetes with β-Cell Failure has established the term to classify severe refractory disease with β-cell failure. Individuals with β-cell failure are at high risk of diabetes-related complications. We propose that diabetes with β-cell failure can be diagnosed when individuals treated with multiple daily insulin injections or insulin pumps meet at least one of the following criteria: fasting C-peptide ≤ 0.6 ng/mL, non-fasting C-peptide ≤ 1.8 ng/mL, 24-hour urine C-peptide < 30 μg/day, or spot urine C-peptide/creatinine ratio ≤ 0.6 nmol/mmol. Among cases of diabetes with β-cell failure, β-cell failure with absolute insulin deficiency can be diagnosed when at least one of the following criteria is met: fasting C-peptide < 0.24 ng/mL, non-fasting C-peptide < 0.6 ng/mL, or spot urine C-peptide/ creatinine ratio < 0.2 nmol/mmol. Multiple daily insulin injections with long-acting insulin analogs and rapid-acting insulin analogs or insulin pumps are required for treatment of diabetes with β-cell failure. Continuous glucose monitoring and an automated insulin delivery system, sensor-augmented pump, or smart insulin pen, along with structured education, are necessary. We call for improvements in the relevant systems to ensure that such treatments can be provided.

The Effects of Subcutaneous Rapid-Acting Insulin Aspart in the Treatment of Mild and Moderate Diabetic Ketoacidosis in Children: A Prospective Study.

Background and objectives The traditional treatment approach to diabetic ketoacidosis (DKA) involves the replacement of fluid and electrolyte deficits and a continuous intravenous infusion of regular insulin. Several clinical trials supported the administration of subcutaneous rapid-acting insulin analogs in the management of uncomplicated DKA. This study aimed to determine the effects/safety of subcutaneous rapid-acting insulin aspart injections in treating uncomplicated mild and moderate DKA in children. Methods In this prospective study in 2022, 25 children with mild/or moderate DKA were enrolled. The main outcome measure was median time (hours) for the resolution of ketoacidosis. Data recorded were as follows: clinical characteristics, severity of ketoacidosis and dehydration, blood glucose, sodium, potassium, creatinine, urine ketones, hospitalization's duration, and complications. Based on the degree of dehydration, fluid deficit was replaced by sodium chloride 0.45%. Insulin aspart 0.15 units/kg subcutaneous injections were given every 2 hours in the hospital outside ICU. Blood glucose was measured hourly and blood gases every 2 hours. Ketoacidosis was considered resolved when the patient did not have nausea/vomiting, was conscious, and could eat, and blood glucose was <250 mg/dL, pH was >7.30, and/or HCO3 was >15 mmol/L. Results Of 25 DKA patients (mean age 11.06±3.89, range 4-17 years, 60% girls), 16 cases (64%) had established type 1 diabetes. Overall, 13 (52%) cases had mild ketoacidosis (average pH=7.25), and 12 (48%) cases had moderate ketoacidosis (average pH=7.15). The mean time to resolution of ketoacidosis was 11.24 hours. All but one patient met DKA recovery criteria without complications. Mild cases compared to moderate cases of DKA had a shorter duration to resolution of DKA (p = 0.04). Mean duration of hospitalization was 2.3 days. No electrolyte disturbances, hypoglycemia events, readmission or mortality, or other adverse effects were observed. Conclusion In children with mild and moderate DKA, subcutaneous rapid-acting insulin aspart administration was an effective, safe, and convenient treatment.

Therapy-Related Satisfaction and Quality of Life for Japanese People with Diabetes Using Rapid-Acting Insulin Analogs: A Web-Based Survey.

People with diabetes require insulin to regulate blood glucose (BG); rapid-acting insulin analogs (RAIA) represent one approach for BG management. New fast-acting RAIA administered at the start of a meal suppress postprandial BG better than conventional RAIA. New RAIA are expected to confer higher treatment satisfaction and improved quality of life (QOL) than conventional RAIA. This cross-sectional, web-based survey in Japan (November 2022) included people with diabetes (type 1/2), aged ≥ 18years, registered in the Rakuten Insight Diabetes Panel, using new and/or conventional RAIA. RAIA-specific satisfaction was evaluated by questions on RAIA use (scores: 1 [not at all satisfied]; 7 [very satisfied]) and QOL by the Diabetes Therapy-Related (DTR)-QOL questionnaire (scores: 0-100, 100 = best) for the whole population (primary endpoint) and for new versus conventional RAIA users (secondary endpoint). Multiple regression models were used to compare new versus conventional RAIA users. The analysis population comprised 217 people with diabetes (new RAIA, n = 109; conventional RAIA, n = 108). Mean (standard deviation) RAIA-specific satisfaction scores ranged from 5.1 (1.2) to 5.4 (1.2); DTR-QOL total score was 51.6 (20.4). RAIA satisfaction scores were numerically higher for new versus conventional RAIA users; no difference in DTR-QOL total score was observed. DTR-QOL satisfaction with treatment domain score was significantly higher in new versus conventional RAIA users (least squares mean difference [standard error]: 7.3 [3.1]; 95% confidence interval: 1.2, 13.4; P = 0.0197). RAIA-specific satisfaction was higher among patients who discussed BG sufficiently with their doctor versus those who did not. New RAIA users have greater treatment satisfaction than conventional RAIA users. QOL was similar among new and conventional RAIA users, except for satisfaction with treatment, which was significantly higher among new RAIA users. Detailed explanations from the doctor to the person with diabetes about the relationship between new RAIA and BG status are essential. A graphical plain language summary is available with this article.

Are New Ultra-Rapid-Acting Insulins Associated with Improved Glycemic Control and Reduced Hypoglycemia in Comparison to Conventional Rapid-Acting Insulins for Individuals with Type 1 and Type 2 Diabetes? A Systematic Review and Meta-Analysis.

Introduction: This study aimed to compare efficacy and safety of ultra-rapid-acting insulin analogs (URAIs; faster aspart [FAsp], ultra-rapid lispro [URLi], and technosphere insulin [TI]) with rapid-acting insulin analogs (RAI) in individuals with type 1 (T1D) or type 2 diabetes (T2D). Methods: Searching for randomized control trial comparing the effects of URAI versus RAI that lasted at least 12 weeks, we initially selected 15 studies for analysis. Three studies involving TI were excluded due to a high degree of heterogeneity. The final meta-analysis included only 12 studies with either FAsp or URLi. Results: Mealtime URAI significantly reduced overall early 1 h postprandial glycemia in individuals with T1D (-20.230 mg/dL [95% confidence interval, 95% CI -24.040 to -16.421]; P < 0.001; I2 = 33.42%) and those with T2D (-9.138 mg/dL [95% CI -12.612 to -5.663]; P < 0.001; I2 = 0%). However, the significant reduction in 2 h postprandial glucose remained only in individuals with T1D (-17.620 mg/dL [95% CI -26.047 to -9.193]; P < 0.001; I2 = 65.88%). These benefits were lost when URAI was administered postmeal. At 24-26 weeks, there was no significant difference in HbA1c between groups, but at 52 weeks, a slight reduction in HbA1c with mealtime URAI was observed (-0.080% [95% CI -0.147 to -0.013]; P = 0.019; I2 = 0%). No difference in weight or the rate of severe or confirmed hypoglycemia was observed. Only individuals with T1D showed a small, but significant increase in early 1-h hypoglycemia with URAI (1.468 [95% CI 1.235 to 1.747]; P < 0.001; I2 = 0%). Conclusion: Mealtime URAI improves 1 and 2 h postprandial glycemic control compared to RAI without increasing hypoglycemia or weight gain.

Safety and Efficacy of Switching SAR341402 Insulin Aspart and Originator Insulin Aspart vs Continuous Use of Originator Insulin Aspart in Adults With Type 1 Diabetes: The GEMELLI X Trial.

SAR341402 insulin aspart (SAR-Asp) is a rapid-acting insulin analog developed as an interchangeable biosimilar to the marketed insulin aspart reference product (NovoLog; NN-Asp). GEMELLI X was a randomized controlled trial to assess outcomes with a biosimilar in line with the US Food and Drug Administration requirements for designation as an interchangeable biosimilar. This report assessed whether multiple switches between SAR-Asp and NN-Asp lead to equivalent safety and efficacy compared with continuous use of NN-Asp in adults with type 1 diabetes (T1D) treated with multiple daily injections, using once-daily insulin glargine U100 (Lantus) as the basal insulin. This open-label randomized (1:1), parallel-group, phase 3 trial compared four × four weeks of alternating use of individually titrated SAR-Asp and NN-Asp (NN-Asp for first four weeks, SAR-Asp in last four weeks; switching group) vs 16 weeks of continuous use of NN-Asp (nonswitching group). End points included pharmacokinetics, immunogenicity, adverse events, hypoglycemia, insulin dose, and change in efficacy parameters. Of the 210 patients randomized, 200 (95.5%) completed the trial. Patients assigned to switching group (n = 104) and nonswitching group (n = 106) showed similar safety and tolerability, including anti-insulin aspart antibody responses, adverse events, and hypoglycemia. At week 16, there was no relevant difference between switching vs nonswitching groups in the change from baseline in glycated hemoglobin (least square [LS] mean difference = 0.05% [95% confidence interval [CI] = -0.13, 0.22]; 0.50 mmol/mol [-1.40, 2.39]), fasting plasma glucose (LS mean difference = 0.23 mmol/L [95% CI = -1.08, 1.53]; 4.12 mg/dL [-19.38, 27.62]), and changes in insulin dosages. Alternating doses of SAR-Asp and NN-Asp compared with continuous use of NN-Asp showed similar safety, immunogenicity, and clinical efficacy in adults with T1D. This study supports interchangeability between SAR-Asp and NN-Asp in T1D management.

Comparative physicochemical and structural characterisation studies establish high biosimilarity between BGL-ASP and reference insulin aspart

Biosimilar insulin analogues are increasing market access for diabetic patients globally. Scientific establishment of biosimilarity is cornerstone of this key change in the medical landscape. BGL-ASP is a biosimilar insulin aspart developed by BioGenomics Limited, India. BioGenomics has considered a stepwise approach in generating the totality of evidence required to establish similarity with reference product. Insulin aspart is a recombinant rapid-acting human insulin analogue utilised in the treatment of type-1 and type-2 diabetes mellitus. The single amino acid substitution at position B28 where proline is replaced with aspartic acid results in a decreased propensity to form hexamers, thus increasing the absorption rate on subcutaneous administration compared to native insulin. In order to establish the safety and efficacy of BGL-ASP, the critical quality attributes (CQAs) of BGL-ASP are identified based on the impact created on biological activity, pharmacokinetic/pharmacodynamic (PK/PD), immunogenicity and safety. The CQAs of insulin aspart are related to product structure, purity and functionality and are characterised using a series of state-of-the-art orthogonal analytical tools. The primary protein sequence, the secondary, tertiary and quaternary structure are found to be highly similar for BGL-ASP and reference product. The product related impurities of insulin aspart and the assay content are determined using high performance liquid chromatography (HPLC) based analysis and is similar for BGL-ASP and reference insulin aspart sourced from United States of America (US), Europe Union (EU) and India. The safety, efficacy and immunogenicity of BGL-ASP is also found to be comparable with reference product and is confirmed through the clinical trials conducted as recommended by International Council for Harmonisation of Technical Requirements of Pharmaceuticals for Human Use (ICH) and European Medicines Agency (EMA) guidelines. The data encompassed in this study demonstrates that reference insulin aspart and BGL-ASP are highly similar in terms of structural, physicochemical, and biological properties, thus confirming its safety and efficacy for usage as potential alternative economical medicinal treatment for diabetes mellitus.

Identification of PK-PD Insulin Models using Experimental GIR Data

We present a method to estimate parameters in pharmacokinetic (PK) and pharmacodynamic (PD) models for glucose insulin dynamics in humans. The method combines 1) experimental glucose infusion rate (GIR) data from glucose clamp studies and 2) a PK-PD model to estimate parameters such that the model fits the data. Assuming that the glucose clamp is perfect, we do not need to know the details of the controller in the clamp, and the GIR can be computed directly from the PK-PD model. To illustrate the procedure, we use the glucoregulatory model developed by Hovorka and modify it to have a smooth non-negative endogeneous glucose production (EGP) term. We estimate PK-PD parameters for rapid-acting insulin analogs (Fiasp and NovoRapid). We use these PK-PD parameters to illustrate GIR for insulin analogs with 30% and 50% faster absorption time than currently available rapid-acting insulin analogs. We discuss the role of system identification using GIR data from glucose clamp studies and how such identified models can be used in automated insulin dosing (AID) systems with ultra rapid-acting insulin.

The Role of Ultra-Rapid-Acting Insulin Analogs in Diabetes: An Expert Consensus.

Ultra-rapid-acting insulin analogs (URAA) are a further development and refinement of rapid-acting insulin analogs. Because of their adapted formulation, URAA provide an even faster pharmacokinetics and thus an accelerated onset of insulin action than conventional rapid-acting insulin analogs, allowing for a more physiologic delivery of exogenously applied insulin. Clinical trials have confirmed the superiority of URAA in controlling postprandial glucose excursions, with a safety profile that is comparable to the rapid-acting insulins. Consequently, many individuals with diabetes mellitus may benefit from URAA in terms of prandial glycemic control. Unfortunately, there are only few available recommendations from authoritative sources for use of URAA in clinical practice. Therefore, this expert consensus report aims to define populations of people with diabetes mellitus for whom URAA may be beneficial and to provide health care professionals with concrete, practical recommendations on how best to use URAA in this context.

THU326 Subcutaneous Insulin Aspart Every 4 Hours In the Treatment Of COVID-19 Patients With Diabetic Ketoacidosis: A Retrospective Study

Abstract Disclosure: D. Chiewchalermsri: None. C. Wanittansirichok: None. C. Sriphrapradang: None. SUBCUTANEOUS INSULIN ASPART EVERY 4 HOURS IN THE TREATMENT OF COVID-19 PATIENTS WITH DIABETIC KETOACIDOSIS: A RETROSPECTIVE STUDY Introduction: COVID-19 infection increases the risk of diabetic ketoacidosis (DKA). To limit the healthcare workers’ exposure when taking care of the COVID-19 patients, treatment of DKA with subcutaneous (SC) rapid-acting insulin analogs every 4 hours was suggested in many professional recommendations. However, the evidence to support this strategy is lacking. We aimed to report the efficacy and safety of SC insulin aspart every 4 hours in the management of DKA in COVID-19 patients. Methods: We retrospectively reviewed all confirmed COVID-19 patients aged &amp;gt;15 years who developed mild-moderate DKA between July 2020 and October 2021 in our institution. Insulin aspart was delivered 0.4 units/kg SC every 4 hours. When blood glucose (BG) decreased to &amp;lt;250 mg/dL, the dose of insulin aspart was reduced to 0.2 units/kg every 4 hours until resolution of DKA. SC Basal insulin 0.15-0.2 units/kg was also initiated at the time of DKA diagnosis. Result: A total of 7 patients had mean age of 67.43±13.19 years with body mass index of 25.49±3.42 kg/m2. Most was 71.4% of female and all had pre-existing type 2 diabetes mellitus. All patients received high-dose steroid for COVID-19 treatment. Initial biochemical parameters were BG of 449±157.3 mg/dL, hemoglobin A1c of 10.58±2.81%, pH of 7.34±0.07, beta-hydroxybutyrate of 4.0±1.51 mmol/L, and HCO3 of 15.5±2.17 mmol/L. Time to resolution of DKA were 12.7±5.82 hours. Conclusion: From our cohort, SC rapid-acting insulin administered every 4 hours could be applied in the selected COVID-19 patients with mild-moderate DKA. Presentation: Thursday, June 15, 2023

Comparison of Insulin Analogs and Human Insulins: A Narrative Review

Abstract Introduction Since insulin analogs have pharmacological properties that are similar to the normal physiological action of insulin, it has been suggested that they provide better glucose control and less rates of hypoglycemia compared to human insulins. Methods We performed a narrative, nonsystematic review of the literature including clinical trials, systematic reviews, meta-analyses, and professional guidelines related to the comparison of human insulins and insulin analogs in terms of glucose control, safety profile, and cost. Results Long-acting basal insulins result in mild improvement in glucose control and less rates of nocturnal hypoglycemic compared to neutral protamine Hagedorn insulin, mainly among patients with type 1 diabetes. Rapid-acting insulin analogs provide better glucose control and lower rates of hypoglycemia compared to regular insulin among patients with type 1 diabetes, whereas no advantage has been shown for insulin analogs among patients with type 2 diabetes for glucose control or hypoglycemia. Premixed insulin analogs provided no advantage in glucose control and inconsistent benefit in lowering the rates of hypoglycemia compared to human premixed insulins among patients with type 2 diabetes. The cost of insulin analogs is significantly higher than human insulins, and favorable cost-effectiveness has only been demonstrated for rapid-acting insulin analogs in type 1 diabetes. Conclusion Currently available evidence supports the use of rapid-acting insulin analogs and possibly long-acting basal insulin over human insulins for patients with type 1 diabetes. For patients with type 2 diabetes, the use of long-acting insulin analogs may be recommended for selected patients who are at an increased risk of significant hypoglycemia, while no clear benefits of meal insulin analogs over human insulins have been observed.

1014-P: Evaluation of Diabetic Ketoacidosis Management with a Subcutaneous Insulin Lispro PowerPlan

Diabetic ketoacidosis (DKA) has traditionally been treated with a continuous intravenous insulin infusion, often requiring management in an intensive care unit (ICU) or step-down unit. There has been growing evidence supporting the use of subcutaneous rapid-acting insulin analogs to treat mild-to-moderate DKA (alert patient able to tolerate oral fluid intake, pH &amp;gt;7.0, bicarbonate ≥10), helping to decrease costs and ICU-bed utilization. We sought to establish the efficacy and safety of a subcutaneous insulin lispro protocol developed at UPMC for the treatment of mild-to-moderate DKA. A retrospective chart review was performed on patients across 15 institutions in the UPMC network from February-October 2022 who had the adult DKA PowerPlan subcutaneous insulin lispro subphase ordered. Of 111 cases analyzed, 47 cases were included that properly used the PowerPlan to treat mild-to-moderate DKA. DKA resolution using the PowerPlan was reached in 45/47 (95.7%) cases. The two unsuccessful cases involved delayed recognition of DKA in the emergency department and premature transition to a prandial insulin regimen before DKA resolution. Hypoglycemia (defined as glucose &amp;lt;70) occurred in 9/47 (19.1%) encounters. Only 1/47 (2.1%) encounters involved hypoglycemia directly attributable to the subcutaneous insulin lispro PowerPlan. The remaining cases of hypoglycemia were attributed to not reducing insulin doses when glucoses were &amp;lt;250, giving insulin doses sooner than 2 hours before the prior dose, not starting dextrose-containing fluids when glucoses were &amp;lt;250, and higher co-administered basal insulin doses (&amp;gt;0.3 units/kg). Overall, these results suggest that a subcutaneous insulin analog can be safely and effectively used to treat mild-to-moderate DKA in non-ICU settings. Disclosure J.Quaytman: None. E.Karslioglu-french: Research Support; Abbott. A.Donihi: None.

Optimisation of induction conditions for a bacterial strain producing proinsulin aspart

Diabetes poses a serious threat to the health of people around the world. Therefore, in 2021, the World Health Organisation launched the Global Diabetes Compact, an initiative aimed at improving the management and prevention of diabetes. The rapid growth in the number of diabetic patients has increased the need for insulin. Rapid-acting human insulin analogues, including insulin aspart, improve the efficacy of insulin therapy. Methods for insulin aspart production include its biosynthesis in the proinsulin form in Escherichia coli. However, the yield of the recombinant protein largely depends on the optimisation of the production process.The aim of the study was to optimise the induction conditions for an E. coli strain expressing recombinant proinsulin aspart through applying the Design of Experiment (DoE) approach to enhance bacterial cell productivity.Materials and methods. The study focused on a strain of E. coli producing proinsulin aspart. The authors planned the experiment using MODDE software and the reduced face-centred central composite design (CCF) enabling the assessment of factor interactions and the creation of design spaces. The authors carried out fermentations of the producing strain in a 5 L Biostat® B bioreactor and measured proinsulin aspart concentrations by capillary gel electrophoresis. The results were analysed using GraphPad Prism 6.Results. Using the DoE approach, the authors optimised the conditions for the growth of the producer strain and the biosynthesis of proinsulin aspart. Based on data from response surface plots for wet biomass concentration, specific productivity, and volumetric productivity, as well as plotted models, the authors established design spaces for the induction of proinsulin aspart expression in E. coli. The plotted models demonstrated high predictive power and high reproducibility of the results. The authors successfully validated the induction process for the synthesis of proinsulin aspart in a bioreactor under optimised conditions. The volumetric productivity of the strain producing proinsulin aspart increased from 3.06±0.16 g/L (conventional conditions) to 4.93±0.80 g/L (optimised conditions).Conclusions. The authors achieved a 60% increase in the volumetric yield of proinsulin aspart. The study results may be used to intensify the industrial production of insulin aspart.

Modern Insulin, Device, and Technology: Tips For Clinicians

Insulin has been a lifesaving treatment for people with diabetes since its discovery in 1921. However, the way insulin is delivered evolved over time. Modern insulin, devices, and technology have transformed the management of diabetes and improved the quality of life for millions of people worldwide.Modern insulins are designed to match the needs of people with diabetes better. Traditional insulins, such as regular and NPH insulin, have a delayed onset and peak, making it difficult to manage blood sugar levels. Newer insulins, such as rapid-acting insulin analogs like aspart, glulisine, and lispro, have a faster onset and shorter duration of action, allowing for greater dosing and timing flexibility. Long-acting insulin analogs, like glargine and detemir, provide more consistent blood sugar control and less hypoglycemia risk.Insulin delivery devices have also advanced significantly. The most common device is the insulin pen, which looks like a large pen and uses disposable insulin cartridges. The pen has replaced traditional syringes and vials for many people with diabetes, offering greater convenience and ease of use. Insulin pumps are also becoming more popular, especially among people with type 1 diabetes. A pump delivers insulin through a catheter inserted under the skin, which can be programmed to provide a continuous infusion of insulin or a bolus dose before meals.Technological advancements have also revolutionized diabetes management. Continuous glucose monitoring (CGM) systems use a small sensor inserted under the skin to measure glucose levels every few minutes, providing real-time data to help people make more informed decisions about insulin dosing and food choices. Some CGM systems also offer alerts for high and low blood sugar levels, making it easier to avoid dangerous fluctuations. Automated insulin delivery systems, also known as closed-loop systems or artificial pancreas systems, use CGM data to automatically adjust insulin delivery, reducing the burden of constant monitoring and decision-making for people with diabetes.In summary, modern insulin, devices, and technology have greatly improved the management of diabetes, allowing for better blood sugar control and a better quality of life for people with diabetes. As technology continues to advance, the future of diabetes management looks promising. Bangladesh J Medicine 2023; Vol. 34, No. 2(1) Supplement: 191

Increased Time in Range with Ultra Rapid Lispro Treatment in Participants with Type 2 Diabetes: PRONTO-Time in Range.

To evaluate time in range metrics and HbA1c in people with type 2 diabetes (T2D) treated with ultra rapid lispro (URLi) using continuous glucose monitoring (CGM) for the first time in this population. This was a Phase 3b, 12-week, single-treatment study in adults with T2D on basal-bolus multiple daily injection (MDI) therapy using basal insulin glargine U-100 along with a rapid-acting insulin analog. Following a 4-week baseline period, 176 participants were newly treated with prandial URLi. Participants used unblinded CGM (Freestyle Libre). Primary endpoint was time in range (TIR) (70-180mg/dl) during the daytime period at Week 12 compared to baseline with gated secondary endpoints of HbA1c change from baseline and 24-h TIR (70-180mg/dl). Improved glycemic control was observed at Week 12 versus baseline including mean daytime TIR (change from baseline [Δ] 3.8%; P = 0.007), HbA1c (Δ - 0.44%; P < 0.001), and 24-h TIR (Δ 3.3%; P = 0.016) with no significant difference in time below range (TBR). After 12weeks, there was a statistically significant decrease in postprandial glucose incremental area under curve, overall, across all meals, within 1h (P = 0.005) or 2h (P < 0.001) after the start of a meal. Basal, bolus, and total insulin dose were intensified with increased bolus/total dose ratio at Week 12 (50.7%) versus baseline (44.5%; P < 0.001). There were no severe hypoglycemia events during the treatment period. In people with T2D, URLi in an MDI regimen was efficacious with improved glycemic control including TIR, HbA1c, and postprandial glucose without increased hypoglycemia/TBR. CLINICALTRIAL REGISTRATION NUMBER: NCT04605991.

Insulin Management for Type 2 Diabetes During Ramadan: A Narrative Review for Clinicians.

Muslims with insulin-dependent type 2 diabetes are at high risk for adverse events while fasting during the month of Ramadan. However, advances in pharmacologic therapy coupled with creative strategies of insulin administration can mitigate complications. This narrative literature review investigates which insulin subtypes are likely to prevent hypoglycemic events and reduce hyperglycemia during the Ramadan fasting season for this high-risk population. Narrative literature review Eligibility Criteria: The following MeSH terms were used: "Diabetes Mellitus, Type 2" and "Insulin," and the "Text Words": "Ramadan", "iftar", "Muslim fast", and "religious fast." The primary focus was on adult, non-pregnant, insulin-dependent type 2 diabetes during Ramadan. Anything beyond this focus was excluded. A total of nine pertinent studies were included for narrative review and analysis. PubMed, EMBASE and Medline. The studies identified suggest long-acting insulins reduce the risk of hypoglycemia, and rapid-acting insulin analogues may improve post-iftar hyperglycemia. Moreover, utilizing flexible glycemic targets during Ramadan is a novel strategy that has demonstrated improved outcomes after the fasting season. Certain insulin subtypes and dosing strategies may be advantageous to use during Ramadan. However, a systematic, comprehensive, and updated review, including a critical appraisal of each original study, is needed to improve clinical care of insulin-dependent type 2 diabetes during Ramadan.

Treatment of acute diabetic metabolic crises in adults (Update2023) : Hyperglycemic hyperosmolar state and ketoacidotic metabolic disorder

Diabetic ketoacidosis (DKA) and the hyperglycemic hyperosmolar state (HHS) represent potentially life-threatening situations in adults. Therefore, rapid comprehensive diagnostic and therapeutic measures with close monitoring of vital and laboratory parameters are required. The treatment of DKA and HHS is essentially the same and replacement of the mostly substantial fluid deficit with several liters of aphysiological crystalloid solution is the first and most important step. Serum potassium concentrations need to be carefully monitored to guide its substitution. Regular insulin or rapid acting insulin analogues can be initially administered as an i.v. bolus followed by continuous infusion. Insulin should be switched to subcutaneous injections only after correction of the acidosis and stable glucose concentrations within an acceptable range.

Role of New Insulin Analogs in the Management of Diabetes. A Clinical Review

This paper has reviewed different insulin analogs currently available in the market and pharma industry, their safety, efficacy and their roles in the diabetes management, comparing with human regular and NPH insulin. Traditional insulins (human regular and NPH insulins) do not have constant or smoother pharmacokinetic and pharmacodynamic profiles and are usually associated with erratic blood glucose profiles with hypoglycemia or hyperglycemia when compared with analog insulins. Similarly they do not match physiologic insulin profiles with basal bolus format. According to the medical literature, current insulin analogs are more efficacious and also it has been documented in research trials that recent insulin analogs are better and safer as compared to human regular and NPH insulin in terms of hypoglycemia and HbA1c reductions. Hence this paper has reviewed these insulins analogs (longer acting basal and rapid acting insulin analogs) for their safety and efficacy in terms of hypoglycemia and HbA1c control, for the management of both type-1 and type-2 diabetics in hospitals and clinics.

Current Insights on the Use of Insulin and the Potential Use of Insulin Mimetics in Targeting Insulin Signalling in Alzheimer's Disease.

Alzheimer's disease (AD) and type 2 diabetes (T2D) are chronic diseases that share several pathological mechanisms, including insulin resistance and impaired insulin signalling. Their shared features have prompted the evaluation of the drugs used to manage diabetes for the treatment of AD. Insulin delivery itself has been utilized, with promising effects, in improving cognition and reducing AD related neuropathology. The most recent clinical trial involving intranasal insulin reported no slowing of cognitive decline; however, several factors may have impacted the trial outcomes. Long-acting and rapid-acting insulin analogues have also been evaluated within the context of AD with a lack of consistent outcomes. This narrative review provided insight into how targeting insulin signalling in the brain has potential as a therapeutic target for AD and provided a detailed update on the efficacy of insulin, its analogues and the outcomes of human clinical trials. We also discussed the current evidence that warrants the further investigation of the use of the mimetics of insulin for AD. These small molecules may provide a modifiable alternative to insulin, aiding in developing drugs that selectively target insulin signalling in the brain with the aim to attenuate cognitive dysfunction and AD pathologies.