Neutral Protamine Hagedorn Insulin Research Articles

Authentication of the shelf-life of NPH injectable insulins samples using NIR and MS spectral fingerprints

Insulin is essential for regulating glucose levels, and its hormonal deficiency leads to diabetes. Treatment involves the use of different types of insulin tailored to individual needs. Properly stored and transported Neutral Protamine Hagedorn (NPH) insulin remains effective and stable, highlighting the importance of quality control to ensure its efficacy and patient safety. This study aims to develop an analytical method to evaluate the shelf-life of NPH injectable insulin samples while preserving packaging integrity. The approach consisted of analyzing intact insulin samples, with and without expired shelf-life dates, using near-infrared spectroscopy (NIR) obtained from two instruments: a benchtop and a portable device. These measurements were coupled with chemometric methods, specifically single-class classification algorithms. The classifiers considered were Data Driven-Soft Independent Modeling of Class Analogy (DD-SIMCA) and One-Class Partial Least Squares (OC-PLS). For benchtop NIR, the DD-SIMCA method, with Savitzky-Golay smoothing preprocessing (41-point window) and baseline offset (BO), achieved excellent results, reaching 100% sensitivity, specificity, and efficiency in both training and test sets. As for portable NIR, the most effective methods were DD-SIMCA and OC-PLS, using datasets preprocessed with Savitzky-Golay smoothing with first derivative, second-order polynomial (SGD-1st-2nd), and 9-point windows combined with Standard Normal Variate (SNV), and Savitzky-Golay smoothing filters (SGS) using second-order polynomial and 7-point windows combined with baseline offset (BO) and Multiplicative Scattering Correction (MSC). The results were corroborated by mass spectrometry, correlating the structural changes of degraded insulin with NIR data. The proposed methodology is a promising tool for non-destructive, rapid, and cost-effective authentication of the preservation state of NPH insulin, aligning with green chemistry principles and allowing for in-situ evaluation, thereby preserving medication integrity.

Cost-Effectiveness of Newer Pharmacologic Treatments in Adults With Type 2 Diabetes: A Systematic Review of Cost-Effectiveness Studies for the American College of Physicians.

In the United States, costs of antidiabetes medications exceed $327 billion. To systematically review cost-effectiveness analyses (CEAs) of newer antidiabetes medications for type 2 diabetes. Bibliographic databases from 1 January 2010 through 13 July 2023, limited to English. Nonindustry-funded CEAs, done from a U.S. perspective that estimated cost per quality-adjusted life-year (QALY) gained for newer antidiabetic medications. Two reviewers screened the literature; disagreements were resolved with a third reviewer. Cost-effectiveness analyses were reviewed for treatment comparisons, model inputs, and outcomes. Risk of bias (RoB) of the CEAs was assessed using Drummond criteria and certainty of evidence (CoE) was assessed using GRADE (Grading of Recommendations Assessment, Development, and Evaluations). Certainty of evidence was determined using cost per QALY thresholds predetermined by the American College of Physicians Clinical Guidelines Committee; low (>$150 000), intermediate ($50 to $150 000), or high (<$50 000) value per QALY compared with the alternative. Nine CEAs were eligible (2 low, 1 high, and 6 some concerns RoB), evaluating glucagon-like peptide-1 agonists (GLP1a), dipeptidyl peptidase-4 inhibitors (DPP4i), sodium-glucose cotransporter-2 inhibitors (SGLT2i), glucose-dependent insulinotropic peptide agonist (GIP/GLP1a), and insulin. Comparators were metformin, sulfonylureas, neutral protamine Hagedorn (NPH) insulin, and others. Compared with metformin, GLP1a and SGLT2i are low value as first-line therapy (high CoE) but may be of intermediate value when added to metformin or background therapy compared with adding nothing (low CoE). Insulin analogues may be similarly effective but more expensive than NPH insulin (low CoE). The GIP/GLP1a value is uncertain (insufficient CoE). Cost-effectiveness analyses varied in methodological approach, assumptions, and drug comparisons. Risk of bias and GRADE method for CEAs are not well established. Glucagon-like peptide-1 agonists and SGLT2i are of low value as first-line therapy but may be of intermediate value when added to metformin or other background therapy compared with adding nothing. Other drugs and comparisons are of low or uncertain value. Results are sensitive to drug effectiveness and cost assumptions. American College of Physicians. (PROSPERO: CRD42022382315).

Determinants of Self-monitoring of Blood Glucose in Iranian Children and Adolescents with Type 1 Diabetes.

Type 1 diabetes mellitus (T1DM) is a prevalent chronic disease among children and adolescents, necessitating effective self-monitoring of blood glucose (SMBG) levels. Understanding the determinants and factors influencing SMBG behavior is crucial for optimizing diabetes management in this population. This study aimed to investigate the frequency of SMBG and identify the determinants influencing factors in children and adolescents with T1DM. This cross-sectional study was conducted in Tehran, Iran, and included 275 participants selected through simple random sampling from the Gabric Diabetes Education Association. The inclusion criteria comprised children and adolescents aged 3 - 18 years diagnosed with T1DM for at least 6 months who were using analog or neutral protamine Hagedorn (NPH) and regular insulin subcutaneously. Patients using insulin pumps were excluded. Data collection involved an online questionnaire covering demographic information (e.g., age, gender, educational status, and parental occupations) as well as clinical information (number of hypoglycemic episodes, hemoglobin A1C (HbA1C) levels, diabetes duration, insulin regimen, diabetes complications, glucose monitoring practices, hospitalizations, and behavioral characteristics). Statistical analyses, including descriptive statistics, correlation tests, and Poisson regressions, were performed using SPSS software (version 21). A significance level of P-value < 0.05 was considered statistically significant. The participants had a mean age of 10.00 ± 3.77 years, with 54.2% being males. Most of the participants (87.3%) were schoolchildren, and the mean age of diagnosis was 6.56 ± 3.73 years, with a mean duration of 44.72 ± 36.32 months. Anthropometric investigations revealed mean height, weight, and body mass index (BMI) values of 136.69 ± 21.11 cm, 37.45 ± 15.51 kg, and 18.31 ± 3.55 kg/m2, respectively. The majority of participants (93.5%) used insulin pens, and the mean daily insulin dosage was 35.34 ± 22.20 IU. Parents reported consistent glucose level monitoring in 64.7% of cases. The mean HbA1c level was 7.91 ± 1.58%. Factors such as the price and availability of glucometer strips influenced glucose level monitoring. In univariate analysis, only age and HbA1C levels showed a negative correlation; however, parents' consistent checking showed a positive correlation with the frequency of daily, weekly, or monthly glucose checking. This study underscores the significance of SMBG in children and adolescents with T1DM. The findings emphasize the critical role of price and availability of glucometers and strips in achieving standard care for T1DM patients.

Safety and efficacy of insulin detemir vs. insulin NPH in pregnant women with diabetes: a systematic review and meta-analysis.

The relative efficacy and safety of insulin neutral protamine Hagedorn (NPH) and detemir (IDet), in the management of diabetes in pregnancy remains unclear. We sought to conduct an updated systematic review and meta-analysis to study the effect of NPH versus IDet during pregnancy on clinically relevant maternal and fetal outcomes. MEDLINE and Google Scholar were queried from inception till September 2022 for original studies comparing NPH with IDet for management of diabetes during pregnancy. Data was pooled using a random-effects model, to generate risk ratios (RR) for dichotomous outcomes and weighted mean differences (WMDs) for continuous outcomes, along with 95% confidence intervals (CIs). I2 test was used to assess the magnitude of heterogeneity. Sensitivity analysis was conducted to explore the potential source of heterogeneity. As less than ten studies were included in our analysis, funnel plots were not made to evaluate publication bias. A P value of ≤0.05 was considered significant in all cases. Our search of the literature yielded 1087 articles initially, of which seven articles comprising 1396 patients, were included in our analysis. All included articles were of reasonably high methodological quality. Our pooled analysis demonstrates no statistically significant difference between the efficacy of insulin Detemir and insulin NPH as assessed by the HbA1c values from baseline. For safety outcomes, insulin detemir was significantly associated with a greater gestational age at delivery (WMD=0.39, 95%CI: 0.07 to 0.71, P=0.02) and lower incidence of hypoglycemic events (RR=0.64, 95%CI: 0.48 to 0.86, P=0.003) in-contrast to insulin NPH. Our findings demonstrate that both, insulin IDet and insulin NPH have a similar efficacy in reducing HbA1c from baseline. However, insulin detemir was associated with lesser incidence of maternal hypoglycemic events and greater gestational age at delivery, compared to NPH.

Comparison of treatment with insulin detemir and NPH in women with gestational diabetes mellitus: glycemic control and pregnancy outcomes. A retrospective study

PurposeThe objective of this retrospective study was to compare glycemic control, pregnancy outcomes, and neonatal outcomes in women with gestational diabetes mellitus (GDM) treated with (a) insulin detemir and (b) insulin neutral protamine Hagedorn (NPH).MethodsA total of 192 women with GDM were included in the analysis. Ninety-eight women received detemir, while 94 women received NPH. Data regarding medical history, glycemic control, and time and mode of delivery, as well as neonatal outcomes, were recorded.ResultsBaseline characteristics were comparable between the two groups. There were no differences with respect to the week of insulin initiation, total insulin dose, duration of insulin therapy, daily insulin dose/weight in early and late pregnancy, or the number of insulin injections per day. Maternal overall weight gain during pregnancy and weight gain per week did not differ either. The detemir group had slightly lower HbA1c levels at the end of gestation [median: det 5.2% (33 mmol/mol) vs NPH 5.4% (36 mmol/mol), p=0.035). There were no cases of hypoglycemia or allergic reactions in the two groups. There were also no differences regarding neonatal outcomes according to the available data, given that data in some cases were missing.ConclusionThe use of insulin detemir was found to be equally effective and safe compared to NPH in women with GDM.

Examining the Effects of Hyperbaric Oxygen Therapy on the Cardiovascular System and Oxidative Stress in Insulin-Treated and Non-Treated Diabetic Rats.

This study explored the effects of hyperbaric oxygen therapy (HBOT) on the cardiovascular system and oxidative stress in streptozotocin-induced diabetic rats. Wistar albino rats were divided into four groups: DM group (diabetic rats), DM+HBOT group (diabetic rats exposed to HBOT for 1 h daily, five days a week, at 2.8 atmosphere absolute (ATA) with 100% oxygen for two weeks), DM+INS group (diabetic rats treated with neutral protamine hagedorn (NPH) insulin at a dosage of 3-5 U/day), and DM+HBOT+INS group (diabetic rats treated with both NPH insulin and HBOT for two weeks). Evaluations included glycemic control, oxidative stress parameters, and cardiac function measurements. NPH insulin treatment reduced blood glucose levels, although normoglycemia was not achieved. The DM+HBOT+INS group demonstrated the lowest pro-oxidative marker levels. NPH insulin treatment improved cardiac function, and combination therapy effectively restored cardiac function in diabetic animals. NPH insulin treatment reduced hyperglycemia and improved cardiac function in diabetic rats. The combined approach of NPH insulin and HBOT resulted in decreased pro-oxidative markers. These findings provide valuable insights for managing cardiovascular complications and oxidative stress in diabetes.

Efficacy of Glargine Insulin Compared with Neutral Protamine Hagedorn Insulin in Patients with Type 2 Diabetes not Controlled with Oral Hypoglycemics: A Cohort Study

Objective: To compare the efficacy of Glargine Insulin with Neutral Protamine Hagedorn (NPH) Insulin in patients with uncontrolled type 2 diabetes with oral hypoglycemic.&#x0D; Study Design: Prospective cohort study.&#x0D; Place and Duration of the Study: Railway Hospital, Rawalpindi Pakistan, from Nov 2020 to Jul 2021.&#x0D; Methodology: All patients aged 30-70 years of either gender, presented with uncontrolled diabetes mellitus on oral hypoglycemic for ≥1 year were enrolled. Patients were divided into Insulin Glargine and injection NPH subcutaneously by lottery method. In both groups, patients were compared for a reduction in HbA1c level after three months of treatment with Insulin. The efficacy was achieved after three months based on a&gt;1% HbA1c level reduction compared to baseline HbA1c.&#x0D; Results: The efficacy of Glargine Insulin was found to be significantly higher, 66(66%), as compared to NPH Insulin, 43(43%) (p-value = 0.002). After adjusting for all other covariates, the efficacy of Glargine Insulin was 3.81 times higher as compared to NPH Insulin (aOR 3.81, 95% CI 1.93-7052). Furthermore, efficacy was 6.95 times higher in patients with ≤25 kg/m2 BMI (aOR 6.95, 95% CI 3.16-15.30), 2.52 times higher in patients with ≤16 years of type 2 diabetes (aOR 2.52, 95% CI 1.30-4.87), 2.77 times higher in patients living in urban areas (aOR 2.77, 95% CI 1.43-5.36).&#x0D; Conclusion: The efficacy of Glargine Insulin was found to be considerably higher than NPH Insulin in patients with type 2 diabetes not controlled with oral hypoglycemia.Keywords: Efficacy, Glargine insulin, NPH insulin, Type 2 diabetes.

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.

Long-acting insulin analogues and the risk of diabetic retinopathy among patients with type 2 diabetes: A population-based cohort study.

To determine whether the use of long-acting insulin analogues is associated with an increased risk of incident diabetic retinopathy (DR) among patients with type 2 diabetes. Using data from the Clinical Practice Research Datalink Aurum, this retrospective, population-based cohort study included patients with type 2 diabetes who initiated a long-acting insulin analogue (glargine, detemir, degludec) or Neutral Protamine Hagedorn (NPH) insulin. The primary outcome was incident DR. We used Cox proportional hazards models with inverse probability of treatment weighting to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for incident DR with insulin analogues versus NPH insulin. There were 66 280 new users of long-acting insulin analogues and 66 173 new users of NPH insulin. The incidence rate of DR was 101.7 per 1000 person-years (95% CI, 98.7-104.8) for insulin analogues and 93.2 (95% CI, 90.0-96.5) per 1000 person-years for NPH insulin. Compared with the current use of NPH insulin, insulin analogues were not associated with the risk of incident DR (HR 1.04, 95% CI, 0.99-1.09). The adjusted HRs were 0.84 (95% CI, 0.66-1.07) for proliferative DR and 1.02 (95% CI, 0.97-1.08) for non-proliferative DR. Compared with NPH insulin, long-acting insulin analogues were not associated with the risk of incident DR among patients with type 2 diabetes. This finding provides important reassurance regarding the safety of long-acting insulin analogues with respect to incident DR.

Intranasal Insulin for the Treatment of Persistent Post-COVID-19 Olfactory Dysfunction.

To investigate if intranasal insulin could be a treatment option for those suffering from recalcitrant olfactory dysfunction due to COVID-19. Prospective interventional cohort with a single group. Sixteen volunteers with anosmia, severe hyposmia, or moderate hyposmia for more than 60 days as sequelae of severe acute respiratory syndrome coronavirus 2 infections were selected for the study. All volunteers reported that standard therapies, such as corticosteroids, have failed to improve their olfactory function. Olfactory function was assessed by the Chemosensory Clinical Research Center test of olfaction (COT) before and after the intervention. Changes in qualitative, quantitative, and global COT scores were investigated. The insulin therapy session consisted of placing into each olfactory cleft 2 pieces of gelatin sponge soaked with neutral protamine Hagedorn (NPH) insulin, 40 IU on each side. The procedure was repeated twice a week for 1 month. Glycaemic blood level was measured before and after each session. The qualitative COT score rose 1.53 points, p = .0001, 95% confidence interval (CI) (-2.12 to -0.94). The quantitative COT score increased by 2.00 points, p = .0002, 95% CI (-3.59 to -1.41). Global COT score had an improvement of 2.01 points, p = .00003, 95% CI (-2.7 to -1.3). Glycaemic blood level dropped on average 10.4 mg/dL, p < .00003, 95% CI (8.1-12.8). Our results suggest that the administration of NPH insulin into the olfactory cleft yields a rapid improvement in the sense of smell of patients suffering from persistent post-COVID-19 olfactory dysfunction. Moreover, the procedure seems to be safe and tolerable.

Modifying Type of Insulin to Manage Steroid-Induced Hyperglycemia: A Case Report.

Steroid-induced hyperglycemia was diagnosed in an older hospitalized patient after he was treated with the intermediate-acting glucocorticoid methylprednisolone. Before hospital admission, the patient did not have a diagnosis of diabetes. His elevated admission glucose level of 167 mg/dL along with his significant hyperglycemia after glucocorticoid initiation prompted the medical team to obtain a hemoglobin A1c result, 8.4%, which confirmed the diagnosis of type 2 diabetes. The capillary blood glucose level was elevated into the 200 to 399 mg/dL range for most of the patient's hospital stay while he was receiving subcutaneous insulin therapy of glargine and aspart correction and prandial bolus dosing. When the patient's subcutaneous insulin therapy was changed from glargine to neutral protamine Hagedorn insulin, the target glucose level range of 140 to 180 mg/dL was attained. From this case report, we determined that it is important to consider modifying subcutaneous insulin therapy by using another type of insulin when target glucose values are not achieved during the treatment of steroid-induced hyperglycemia.

Twice-daily injections and multiple daily injections of insulin in toddlers with type 1 diabetes: a retrospective cohort study.

Twice-daily injections and multiple daily injections of insulin in toddlers with type 1 diabetes: a retrospective cohort study.

NPH Insulin Versus Insulin Glargine Versus NPH Insulin Plus Insulin Glargine for the Treatment of Dexamethasone-Induced Hyperglycemia in Patients With COVID-19: A Retrospective Cohort Study.

Dexamethasone use in patients hospitalized with COVID-19 significantly reduces mortality; however, it commonly results in hyperglycemia. Optimal treatment of dexamethasone-induced hyperglycemia is not well established. The study purpose was to assess the difference in blood glucose (BG) control between insulin glargine, neutral protamine hagedorn (NPH) insulin, and insulin glargine plus NPH insulin for dexamethasone-induced hyperglycemia in patients with type 2 diabetes (T2DM) and COVID-19 infection. This retrospective study was conducted in adult inpatients with T2DM and COVID-19 infection who received 6 mg of dexamethasone once daily and insulin during the 5-day study period. The primary outcome was the difference in mean point-of-care (POC) BG levels between study insulins. Secondary outcomes included the incidence of hyperglycemia and hypoglycemia, length of stay, and the percent difference between the mean daily inpatient and home basal insulin doses (for patients who were receiving basal insulin prior to admission in the insulin glargine and insulin glargine and NPH insulin groups only). Ninety-six patients were included in the analysis (67 insulin glargine, 10 NPH insulin, and 19 insulin glargine plus NPH insulin). The difference in mean POC BG level was not different among groups (254 ± 60 mg/dL vs 234 ± 39 mg/dL vs 250 ± 51 mg/dL, respectively; P = 0.548). There were no significant differences in the secondary outcomes. No difference in the mean POC BG level was observed. Dexamethasone-induced hyperglycemia was poorly controlled in patients with T2DM and COVID-19 infection.

Long-term field study of lispro and neutral protamine Hagedorn insulins treatment in dogs with diabetes mellitus.

The long-term clinical and biofhemical effects of basal-bolus insulin treatment with lispro and NPH in dogs with diabetes mellitus are undocumented. To perform a prospective pilot field study of the long-term effects of lispro and NPH on clinical signs and serum fructosamine concentrations (SFC) in dogs with diabetes mellitus. Twelve dogs received combined lispro and NPH insulins treatment twice a day and were examined every 2 weeks for 2 months (visits 1-4), and every 4 weeks for up to 4 additional months (visits 5-8). Clinical signs and SFC were recorded at each visit. Polyuria and polydipsia (PU/PD) were scored as absent (0) or present (1). Median (range) PU/PD scores of combined visits 5-8 (0, 0-1) were significantly lower than median scores of combined visits 1-4 (1, 0-1, p = 0.03) and at enrolment (1, 0-1, p = 0.045). Median (range) SFC of combined visits 5-8 (512mmol/L, 401-974mmol/L) was significantly lower than SFC of combined visits 1-4 (578mmol/L, 302-996mmol/L, p = 0.002) and at enrolment (662mmol/L, 450-990mmol/L, p = 0.03). Lispro insulin dose was significantly and negatively, albeit weakly, correlated with SFC concentration during visits 1 through 8 (r = -0.3, p = 0.013). Median duration of follow up was 6 months (range 0.5-6) and most dogs (8, 66.7%) were followed for 6 months. Four dogs withdrew from the study within 0.5-5 months because of documented or suspected hypoglycaemia, short NPH duration or sudden unexplained death. Hypoglycaemia was noted in 6 dogs. Long-term lispro and NPH combination therapy may improve clinical and biochemical control of some diabetic dogs with comorbidities. Risk of hypoglycaemia should be addressed with close monitoring.

Glycaemic Control in People with Type 2 Diabetes Mellitus Switching from Basal Insulin to Insulin Glargine 300 U/ml (Gla-300): Results from the REALI Pooled Database.

Using pooled data from the REALI European database, we evaluated the impact of previous basal insulin (BI) type on real-life effectiveness and safety of switching to insulin glargine 300 U/ml (Gla-300) in people with suboptimally controlled type 2 diabetes. Patient-level data were pooled from 11 prospective, open-label, 24-week studies. Participants were classified according to the type of prior BI. Of the 4463 participants, 1282 (28.7%) were pre-treated with neutral protamine Hagedorn (NPH) insulin and 2899 (65.0%) with BI analogues (BIAs), and 282 (6.3%) had undetermined prior BI. There were no meaningful differences in baseline characteristics between subgroups, except for a higher prevalence of diabetic neuropathy in the NPH subgroup (21.6% versus 7.8% with BIAs). Mean ± standard deviation haemoglobin A1c (HbA1c) decreased from 8.73 ± 1.15% and 8.35 ± 0.95% at baseline to 7.71 ± 1.09% and 7.82 ± 1.06% at week 24 in the NPH and BIA subgroups, respectively. Least squares (LS) mean change in HbA1c was - 0.85% (95% confidence interval - 0.94 to - 0.77) in NPH subgroup and - 0.70% (- 0.77 to - 0.64) in BIA subgroup, with a LS mean absolute difference between subgroups of 0.16 (0.06-0.26; p = 0.002). Gla-300 mean daily dose was slightly increased at week 24 by 0.07 U/kg/day (approximately 6 U/day) in both subgroups. Incidences of symptomatic and severe hypoglycaemia were low, without body weight change. Irrespective of previous BI therapy (NPH insulin or BIAs), switching to Gla-300 improved glycaemic control without weight gain and with low symptomatic and severe hypoglycaemia incidences. However, a slightly greater glucose-lowering effectiveness was observed in people pre-treated with NPH insulin.

ODP620 A Cross-over Trial Using Insulin Glargine And Neutral Protamine Hagedorn Insulin For The Poorly Controlled Patients With Type 2 Diabetes Who Refused Multiple Daily Insulin Injections

Abstract A Cross-Over Trial Using Insulin Glargine and Neutral Protamine Hagedorn insulin for the Poorly Controlled Patients with Type 2 Diabetes Who Refused Multiple Daily Insulin Injections Background: Data in the literature describing the comparison between Neutral Protamine Insulin of Hagedorn (NPH) and glargine insulins are conflicting. While some studies revealed the superiority of Glargine, others had shown comparable results and even NPH superiority figures. We have many patients on NPH basal therapy in our clinical practice and another good number on Glargine. We did observe adverse effects in both groups, but local data and real numbers comparing both regimens are lacking. Objective To compare basal insulin regimen using NPH or Glargine in efficacy, hypoglycaemic events, and weight gain. Design and setting: A prospective interventional crossover study was conducted in Faiha Specialized Diabetes, Endocrine and Metabolism Center from 2018 through 2021, involving patients less than 65 years old with uncontrolled Type 2 Diabetes Mellitus whose HbA1c &amp;gt;10% on oral antidiabetic drugs (OAD); randomized into two groups (G1 &amp; G2), 70 patients in each group had completed the study, one group received NPH and the other received Glargine in addition to their OAD for one year, then they were crossed over for another one year after a period of washout. Results The mean age was 48.9±5.5 and 45.9±4.1 years for G1 and G2, respectively. 36(51.4%) in G1 were women versus 27(38.6%) in G2. In the first phase of the study, HbA1c reduction was 5.5±1.1% for the NPH group and 5.3±1.1% for the Glargine group (p=0.418), there was 1.7±2.7 versus 1.1±2.9 Kg weight gain (p=0.209), 27(39.7%) hypoglycemic event versus 26(37.7%) (p=0.883) and 5 patients(7.4%) achieved HbA1c &amp;lt;7% versus 8(11.6%) (p=0.397) for the patients in NPH and Glargine groups respectively. While in the crossover phase, the data comparing Glargine and NPH groups are as following: 0.6±0.8 versus 0.5±0.9% reduction in HbA1c (p=0.413), 1.7±3.1 versus 0.6±2.2 Kg weight loss (p=0. 035) although the final weight was not much different 77.3±12. 0 versus 77.7±11.5 (p=0.841), 16(27.1%) versus 23(36.5%) hypoglycemic events (p=0.493) and 17(29.8%) versus 11(17.7%) achieved HbA1c&amp;lt;7% (p=0.121) respectively. Conclusion In our study, there was no significant difference in HbA1c reduction, Hypoglycemic events, and weight gain between patients using NPH or Glargine basal insulin regimen. Keywords: Diabetes; Glargine; NPH. Presentation: No date and time listed

The association of long-acting insulin analogue use versus neutral protamine Hagedorn insulin use and the risk of major adverse cardiovascular events among individuals with type 2 diabetes: A population-based cohort study.

To compare the risk of cardiovascular outcomes associated with long-acting insulin analogues versus neutral protamine Hagedorn (NPH) insulin among patients with type 2 diabetes. We conducted a population-based retrospective cohort study using the UK Clinical Practice Research Datalink Aurum, linked with hospitalization and vital statistics data. Patients with type 2 diabetes who initiated basal insulin treatment between 2002 and 2018 were included in the study. Exposure was defined as current use of long-acting insulin analogues or NPH insulin, defined using a time-varying approach. The primary outcome was major adverse cardiovascular events (MACE; a composite endpoint of myocardial infarction, ischaemic stroke and cardiovascular death). We used a marginal structural Cox proportional hazards model to estimate the hazard ratio (HR) and 95% confidence interval (CI) for MACE with current use of long-acting insulin analogues versus NPH insulin, and in secondary analyses, by long-acting insulin molecule. Our cohort included 57 334 patients. A total of 3494 MACE occurred over a mean follow-up of 1.6 years (incidence rate 37.4, 95% CI 36.2 to 38.7 per 1000 person-years). Long-acting insulin analogues were associated with a decreased risk of MACE compared to NPH insulin (HR 0.89, 95% CI 0.83 to 0.96). Current use of long-acting insulin analogues is associated with a modestly reduced risk of MACE compared to current use of NPH insulin among patients with type 2 diabetes. This study could have important implications for drug plan managers and guideline-writing committees for recommendations of insulin treatment for type 2 diabetes.

Safety and efficacy of insulin detemir versus NPH in the treatment of diabetes during pregnancy: Systematic review and meta-analysis of randomized controlled trials

AimsTo compare the safety and efficacy of insulin detemir versus neutral protamine Hagedorn (NPH) in pregnant women with diabetes. MethodsMEDLINE, CENTRAL, Google Scholar databases, and ClinicalTrials.gov registry were searched from inception to December 2021 to identify randomized controlled trials (RCTs) concerning adult women with singleton pregnancies, gestational or pregestational diabetes, and the need for insulin therapy. A systematic review and a meta-analysis (weighted data, random-effects model) were performed. Continuous outcomes were expressed as mean difference (MD) with 95% confidence interval (CI) (inverse variance method); dichotomous outcomes were expressed as risk ratio (RR) with 95% CI (Mantel-Haenszel method). Heterogeneity was quantified using the I2 index. ResultsFive RCTs involving 1450 participants met the inclusion criteria. Outcomes that showed significant results in favor of insulin detemir over NPH were maternal hypoglycemic events (RR 0.64, 95% CI 0.48–0.86, p = 0.003; I2 = 0%) and gestational age at delivery (MD 0.48, 95% CI 0.16–0.81, p = 0.003; I2 = 0%). ConclusionsInsulin detemir was associated with less maternal hypoglycemic events and decreased risk for prematurity compared with NPH insulin. More research should be conducted to reach a safe conclusion about the optimal insulin regimen for women with diabetes in pregnancy.

Twenty Years of Insulin Gla-100: A Systematic Evaluation of Its Efficacy and Safety in Type 2 Diabetes Mellitus.

IntroductionThis systematic review aims to present the current evidence base with respect to the initiation and intensification of insulin therapy with glargine 100 U/mL (Gla-100) compared to other insulins in people with type 2 diabetes mellitus (T2DM).MethodsA systematic literature search of PubMed (MEDLINE), EMBASE, and the Cochrane Central Register of controlled clinical trials databases was performed to identify studies published up to September 30, 2020 that compared the effects of Gla-100 to that of other insulin regimens in people with T2DM. Relevant information pertaining to the predefined outcomes of interest was extracted. Glycated hemoglobin (HbA1c) change and response rates along with overall hypoglycemia incidence were the primary efficacy and safety outcomes of interest.ResultsSeventy-nine studies (63 interventional and 16 non-interventional) in which Gla-100 was either initiated in previously insulin-naïve patients (n = 57) or used in an intensified regimen (n = 22) were identified and evaluated. In insulin-naïve patients, most studies demonstrated that Gla-100 was significantly better compared with premixed insulins and similar compared with neutral protamine Hagedorn (NPH) insulin, second-generation basal insulins, co-formulations, and other first-generation basal insulins in terms of the primary efficacy parameters. Overall hypoglycemia risk with Gla-100 was significantly lower compared with NPH, premixed, coformulation, and other first-generation basal insulins and significantly higher compared with second-generation basal insulins. In studies with intensified regimens, efficacy outcomes with Gla-100 were significantly better compared with insulin detemir (IDet); similar compared with NPH, second-generation basal insulins, co-formulations; and with premixed insulins. In these studies, overall hypoglycemia risk with Gla-100 was significantly lower compared with IDet and comparable to NPH, premixed insulins, co-formulations, and second-generation basal insulins. In addition, most intensification studies also revealed a significantly lower risk of nocturnal hypoglycemia with Gla-100–based regimens versus NPH and premixed insulins and a significantly greater risk compared to second-generation basal insulins.ConclusionsThe evidence presented in this review suggests that Gla-100 is an effective option for both insulin initiation and intensification strategies used in the management of T2DM.Supplementary InformationThe online version contains supplementary material available at 10.1007/s13300-022-01284-2.

Efficacy and Safety of Insulin Glargine 300U/mL in People with Type2 Diabetes Uncontrolled on Basal Insulin: The 26-Week Interventional, Single-Arm ARTEMIS-DM Study.

IntroductionThe efficacy and safety of switching to insulin glargine 300 U/mL (Gla-300) in type 2 diabetes mellitus (T2DM) uncontrolled on basal insulin (BI) has been demonstrated in the North American and Western European populations; however, there is limited data from other geographical regions with different ethnicities. The ARTEMIS-DM study aimed to evaluate the efficacy and safety of Gla-300 in people with T2DM uncontrolled on BI from Asia, Latin America and Middle East Africa.MethodsThe ARTEMIS-DM was a 26-week, prospective, interventional, single-arm, phase IV study (NCT03760991). Adults with T2DM previously uncontrolled (glycated haemoglobin [HbA1c] 7.5–10%) on BI were switched to Gla-300. The primary endpoint was change in HbA1c from baseline to 26 weeks. Key secondary endpoints were changes in HbA1c (week 12), fasting plasma glucose (FPG), self-monitored plasma glucose (SMPG) and BI dose from baseline to week 26. The safety and tolerability of Gla-300 were also assessed.ResultsA total of 372 (50% male) participants were included, with mean (standard deviation [SD]) age 60.9 (10.0) years, duration of diabetes 13.11 (7.48) years and baseline HbA1c 8.67 (0.77)% (71.22 [8.44] mmol/mol). A total of 222 (59.7%) participants were using insulin glargine 100 U/mL and 107 (28.8%) were using neutral protamine Hagedorn insulin as previous BI. There were clinically significant reductions in mean HbA1c (− 0.82%; primary endpoint), FPG and SMPG levels at week 26. With a pre-defined titration algorithm, mean Gla-300 dose increased from 27.48 U (0.35 U/kg) at baseline to 39.01 U (0.50 U/kg) at week 26. Hypoglycaemia events occurred in 20.4% of the participants; 1 (0.3%) participant had a severe hypoglycaemia event.ConclusionIn people with T2DM uncontrolled on previous BI, switching to Gla-300 with optimal titration guided by an algorithm was associated with improved glycaemic control and low incidence of hypoglycaemia across multiple geographic regions.ClinicalTrials.gov identifierNCT03760991.Supplementary InformationThe online version contains supplementary material available at 10.1007/s13300-022-01271-7.