Safety and Efficacy of Insulins in Critically Ill Patients Receiving Continuous Enteral Nutrition.

OBJECTIVE: There is a relative lack of consensus regarding the optimal management of hyperglycemia in patients receiving continuous enteral nutrition (EN), with or without a diagnosis of diabetes. METHODS: This retrospective study examined 475 patients (303 with known diabetes) hospitalized in critical care setting units in 2019 in a single center who received continuous EN. Rates of hypoglycemia, hyperglycemia, and glucose levels within the target range (70-180 mg/dL) were compared between patients with and without diabetes, and among patients treated with intermediate-acting (IA) biphasic neutral protamine Hagedorn 70/30, long-acting (LA) insulin, or rapid-acting insulin only. RESULTS: Among those with type 2 diabetes mellitus, IA and LA insulin regimens were associated with a significantly higher proportion of patient-days in the target glucose range and fewer hyperglycemic days. Level 1 (<70 mg/dL) and level 2 (<54 mg/dL) hypoglycemia occurred rarely, and there were no significant differences in level 2 hypoglycemia frequency across the different insulin regimens. CONCLUSION: Administration of IA and LA insulin can be safe and effective for those receiving insulin doses for EN-related hyperglycemia.

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

BACKGROUND: 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). METHODS: Evaluations included glycemic control, oxidative stress parameters, and cardiac function measurements. RESULTS: 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. CONCLUSIONS: 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.

Comparison of regular with NPH insulin vs. premix insulin in children and adolescents with type 1 diabetes in a resources-limited setting: a retrospective data analysis.

OBJECTIVES: Few studies addressed the efficacy of human insulin regimens (mostly premix insulin) used in many low-and-middle income countries on glycemic control of children and adolescents with diabetes. The aim of this study was to assess the efficacy of the premix insulin on the glycated hemoglobin (HbA1c) in comparison to the regular with NPH insulin scheme. METHODS: A retrospective study was carried out from January 2020 to September 2022 on patients with type 1 diabetes aged below 18 years followed in Burkina Life For A Child program. They were categorized into three groups, on regular with NPH insulin (Group A), on premix insulin (Group B) and on regular with premix insulin (Group C). Outcome was analyzed based on HbA1c level. RESULTS: Sixty-eight patients with a mean age of 15.38 ± 2.26 years and the sex ratio (M/W) 0.94 were studied. There were 14 in Group A, 20 in Group B, and 34 patients in Group C. The mean HbA1c value in the corresponding insulin regimen was 12.8 ± 1.39%, 9.87 ± 2.18%, and 10.66 ± 2.1%, respectively. Glycemic control was better in Groups B and C than Group A (p<0.05) but there was no difference between groups B and C. CONCLUSIONS: Our results indicate that the use of premix insulin gives a better glycemic control than NPH insulin. However, further prospective study of these insulin regimens with a strengthening education strategy and glycemic control by continuous glucose monitoring and HbA1c is required to corroborate these preliminary findings.

Gestão de riscos como melhoria para a aquisição e distribuição de insulinas pelo SUS / Risk management as an improvement for the acquisition and distribution of insulins by SUS

Objetivo: identificar a melhoria por meio da gestão de risco aplicada aos processos de aquisição e distribuição de insulinas humanas NPH. Método: O estudo foi realizado por etapas: em 1º momento foram realizadas reuniões (Brainstorming) e em 2º momento foi elaborado um formulário eletrônico em forma de questionário sendo mostrado os "eventos" de riscos com os pesos inerentes à probabilidade e ao impacto que geraram o risco inerente aos processos de aquisição e distribuição de insulinas humanas NPH e Regular pelo Ministério da Saúde. Resultados: Considerando os processos houve maior incidência de riscos médios. Não foi apontado risco muito baixo, não foi identificado risco extremo e foram apresentados apenas 02 (dois) riscos altos. Conclusão: A gestão de risco do referido estudo é uma ferramenta de melhoria para os processos de aquisição e distribuição de insulinas humanas NPH e Regular pelo Ministério da Saúde.(AU)

Objective: to identify improvement through risk management applied to the acquisition and distribution processes of NPH human insulins. Method: The study was carried out in stages: in the 1st moment, meetings were held (Brainstorming) and in the 2nd moment, an electronic form was elaborated in the form of a questionnaire, showing the risk "events" with the weights inherent to the probability and impact they generated the risk inherent in the acquisition and distribution processes of NPH and Regular human insulins by the Ministry of Health. Results: Considering the processes, there was a higher incidence of medium risks. No very low risk was indicated, no extreme risk was identified and only 02 (two) high risks were presented. Conclusion: The risk management of the aforementioned study is an improvement tool for the processes of acquisition and distribution of NPH and Regular human insulins by the Ministry of Health.(AU)

The efficacy of insulin degludec and insulin glargine over NPH insulin among toddlers and preschoolers with type 1 diabetes using glycemic variability and time in range.

Optimizing glycemic control without risking hypoglycemia is crucial in toddlers and preschoolers with type 1 diabetes (T1D) to avoid cognitive impairment later in life. Hence, this study aims to compare glycemic parameters among toddlers and preschoolers with T1D in relation to different basal insulins. Sixty toddlers and preschoolers with T1D with mean age of 3.53 ± 1.17 years (range, 2-6) and mean diabetes duration of 9.37 ± 1.85 months were randomly assigned into three equal groups; group A received insulin degludec, group B received insulin glargine, and group C were on NPH. At baseline, the three groups were matched regarding clinical and laboratory parameters (p > 0.05). They were followed up at 3 and 6 months for insulin daily dose (IDD), hypoglycemia and severe-hypoglycemia frequency, and glycated hemoglobin (HbA1c). At the study endpoint, continuous glucose monitoring (CGM) was assessed in a random sample of 10 patients from each group. The mean time in range (TIR) of the studied cohort was 55.07 ± 24.05%, and their mean coefficient of variation (CV) was 42.82 ± 11.69%. The TIR was significantly higher in the degludec group (69.36 ± 18.54) and the glargine group (55.43 ± 26.51) than the NPH group (32.56 ± 9.11), p < 0.001. Meanwhile, the CV was significantly lower in the degludec group (35.12 ± 6.47) than the gargine (44.1 ± 13.13) and the NPH (53.8 ± 7.54) groups, p < 0.001. The insulin degludec and glargine groups had significantly lower HbA1c (p = 0.002), hypoglycemia (p = 0.006), severe hypoglycemia (p = 0.029), and IDD (p = 0.015) than the NPH group. CONCLUSION: Insulin degludec and glargine resulted in better HbA1c and TIR with reduced hypoglycemia and IDD than NPH among toddlers and preschoolers with T1D. Moreover, CV was lowest in the insulin degludec group. WHAT IS KNOWN: • Insulin therapy is the mainstay of T1D management. • Optimal insulin therapy for young children with T1D should provide effective glycemic. WHAT IS NEW: • Insulin degludec and insulin glargine have better efficacy than NPH insulin among toddlers and preschoolers with T1D in the term of significantly lower coefficient of variation, HbA1c and IDD and significantly higher time in range. • Insulin degludec and insulin glargine have better safety in the term of less hypoglycemia and severe hypoglycemia episodes than NPH insulin among toddlers and preschoolers with T1D.

Use of insulin glargine during pregnancy: A review.

BACKGOUND AND AIMS: Hyperglycemia during pregnancy is increasing globally. Insulin therapy is considered the standard of care for its optimum management. Insulin glargine, in spite of widespread use in non-pregnant adults, lacks randomized controlled trial evidence as safe basal insulin during pregnancy. Aim of this review is to discuss major available evidences and recommendations on the use of insulin glargine during pregnancy. METHODS: Evidences related to use of insulin glargine during pregnancy, including animal studies, placental transfer studies, case reports as well as observational studies were retrieved using PUBMED & Google scholar. Recommendations regarding use of insulin glargine during pregnancy by international and Indian organizations were reviewed. RESULTS: Trans-placental transfer studies show that insulin glargine does not cross placenta when used at therapeutic concentrations. Although there are no randomized controlled trials on insulin glargine in pregnancy, it's use during pregnancy is not associated with any adverse maternal or neonatal outcomes as shown in many case reports and observational studies (both prospective and retrospective). It's use during pregnancy is hence considered safe by many organizations across the globe. CONCLUSIONS: Insulin glargine can be continued safely during pregnancy in women who are already taking it prior to pregnancy and have achieved good glycemic control with it. However we require preferably randomized controlled trials or large prospective observational studies to establish it as first line or preferred basal insulin for management of hyperglycemia during pregnancy.

Study rationale and design of the EANITIATE study (EmpAgliflozin compared to NPH Insulin for sTeroId diAbeTEs) - a randomized, controlled, multicenter trial of safety and efficacy of treatment with empagliflozin compared with NPH-insulin in patients with newly onset diabetes following initiation of glucocorticoid treatment.

BACKGROUND: A well-known metabolic side effect from treatment with glucocorticoids is glucocorticoid-induced diabetes mellitus (GIDM). Guidelines on the management of GIDM in hospitalized patients (in the non-critical care setting), recommend initiation of insulin therapy. The scientific basis and evidence for superiority of insulin therapy over other glucose lowering therapies is however poor and associated with episodes of both hypo- and hyperglycaemia. There is an unmet need for an easier, safe and convenient therapy for glucocorticoid-induced diabetes. METHODS: EANITIATE is a Danish, open, prospective, multicenter, randomized (1:1), parallel group study in patients with new-onset diabetes following treatment with glucocorticoids (> 20 mg equivalent prednisolone dose/day) with blinded endpoint evaluation (PROBE design). Included patients are randomized to either a Sodium-Glucose-Cotransporter 2 (SGLT2) inhibitor or neutral protamin Hagedorn (NPH) insulin and followed for 30 days. Blinded continuous glucose monitoring (CGM) will provide data for the primary endpoint (mean daily blood glucose) and on glucose fluctuations in the two treatment arms. Secondary endpoints are patient related outcomes, hypoglycaemia, means and measures of variation for all values and for time specific glucose values. This is a non-inferiority study with the intent to demonstrate that treatment with empagliflozin is not inferior to treatment with NPH insulin when it comes to glycemic control and side effects. DISCUSSION: This novel approach to management of glucocorticoid-induced hyperglycemia has not been tested before and if SGLT2 inhibition with empaglifozin compared to NPH-insulin is a safe, effective and resource sparing treatment for GIDM, it has the potential to improve the situation for affected patients and have health economic benefits. TRIAL REGISTRATION: www.clinicaltrialsregister.eu no.: 2018-002640-82. Prospectively registered November 20th. 2018. Date of first patient enrolled: June 4th. 2019. This protocol article is based on the EANITATE protocol version 1.3, dated 29. January 2018.

Successful Treatment with Bedtime Basal Insulin Added to Metformin without Weight Gain or Hypoglycaemia over Three Years.

The aim of this observational study was to follow-up patients with bedtime basal insulin (NPH insulin) added to metformin. In 285 patients with type 2 diabetes, a therapy with bedtime basal insulin added to metformin was started due to failure to achieve a glycaemic goal. Up until July 2019, 272 patients (95.4%) were followed-up (59.5 y, 92.6 kg, diabetes duration 6.6 y, HbA1c 8.4%/68.6 mmol/mol). HbA1c decreased by -1.2% and bodyweight by -1.7 kg after a duration of 31.7 ± 29.1 (range 2-133) months. Severe hypoglycaemia did not occur. In 144/272 patients (52.9%), the therapeutic goal for HbA1c was achieved over 32.7 months. In 69/272 patients (25.4%), the HbA1c target was achieved over 25.0 months (afterwards, therapy with basal insulin was discontinued because HbA1c was under target). In 36/272 patients (13.2%), the HbA1c goal was achieved until the submission of this manuscript (mean duration of treatment 57.4 ± 28.2 (range 13-121) months). Over 90% of patients with type 2 diabetes and failure of metformin reached their HbA1c goal with additional basal insulin at bedtime over several years in association with a reduction of bodyweight and without any event of severe hypoglycaemia.

Management of hyperglycaemia in persons with non-insulin-dependent type 2 diabetes mellitus who are started on systemic glucocorticoid therapy: a systematic review.

OBJECTIVES: What is the most effective pharmacological intervention for glycaemic control in known type 2 diabetes mellitus (DM) without prior insulin treatment and newly started on systemic glucocorticoid therapy? DESIGN: We conducted a systematic literature review. DATA SOURCES: We searched MEDLINE, Embase and Cochrane Library databases and Google for articles from 2002 to July 2018. ELIGIBILITY CRITERIA: We combined search terms relating to DM (patients, >16 years of age), systemic glucocorticoids, glycaemic control, randomised controlled trials (RCTs) and observational studies. DATA EXTRACTION AND SYNTHESIS: We screened and evaluated articles, extracted data and assessed risk of bias and quality of evidence according to Grading of Recommendations Assessment, Development and Evaluation guidelines. RESULTS: Eight of 2365 articles met full eligibility criteria. Basal-bolus insulin (BBI) strategy for patients under systemic glucocorticoid therapy was comparatively effective but provided insufficient glucose control, depending on time of day. BBI strategy with long-acting insulin and neutral protamin Hagedorn as basal insulin provided similar overall glycaemic control. Addition of various insulin strategies to standard BBI delivered mixed results. Intermediate-acting insulin (IMI) as additional insulin conferred no clear benefits, and glycaemic control with sliding scale insulin was inferior to BBI or IMI. No studies addressed whether anticipatory or compensatory insulin adjustments are better for glycaemic control. CONCLUSION: The lack of suitably designed RCTs and observational studies, heterogeneity of interventions, target glucose levels and glucose monitoring, poor control of DM subgroups and low to moderate quality of evidence render identification of optimal pharmacological interventions for glycaemic control and insulin management difficult. Even findings on the widely recommended BBI regimen as intensive insulin therapy for patients with DM on glucocorticoids are inconclusive. High-quality evidence from studies with well-defined DM phenotypes, settings and treatment approaches is needed to determine optimal pharmacological intervention for glycaemic control. PROSPERO REGISTRATION NUMBER: CRD42015024739.

A 26-week, randomized trial of insulin detemir versus NPH insulin in children and adolescents with type 2 diabetes (iDEAt2).

There are limited studies evaluating the safety and efficacy of treatments in young people with type 2 diabetes (T2D). This study compared the efficacy and safety of insulin detemir versus neutral protamine Hagedorn (NPH) insulin, both in combination with metformin and lifestyle intervention, in children and adolescents with T2D. This randomized, open-label, phase 3 trial recruited patients (n = 42) aged 10-17 years diagnosed with T2D already receiving metformin ± other oral antidiabetic drugs ± basal insulin. Patients were randomized (1:1) to receive either insulin detemir or NPH insulin, both with the maximum tolerated dose of metformin, and lifestyle intervention, over 26 weeks. Enrollment terminated prematurely after 17 months due to a very slow recruitment rate (12% of the target met). After 26 weeks, the observed mean HbA1c value had decreased by 0.61% points in the insulin detemir group vs. 0.84% points in the NPH insulin group. The rate of symptomatic blood glucose-confirmed hypoglycemic episodes was 0.4 episodes/patient-year of exposure (PYE) for insulin detemir vs. 1.1 episodes/PYE for NPH insulin. CONCLUSION: No safety issues were revealed with either basal insulin. Due to the low number of patients recruited, no efficacy conclusions could be drawn. ClinicalTrials.gov identifier: NCT02131272. What is known: • There is a growing worldwide epidemic of type 2 diabetes in children and adolescents. • There is a lack of research and limited treatment options currently available in this population. What is new: • No safety issues with insulin detemir or neutral protamine Hagedorn insulin in children and adolescents with type 2 diabetes were observed. • Improving clinical trial recruitment, along with providing early, efficacious, and safe treatment options, in this population is critical.

Insulin glargine affects the expression of Igf-1r, Insr, and Igf-1 genes in colon and liver of diabetic rats.

OBJECTIVES: The mitogenic effect of the analogous insulin glargine is currently under debate since several clinical studies have raised the possibility that insulin glargine treatment has a carcinogenic potential in different tissues. This study aimed to evaluate the Igf-1r, Insr, and Igf-1 gene expression in colon and liver of streptozotocin-induced diabetic rats in response to insulin glargine, neutral protamine Hagedorn (NPH) insulin, and metformin treatments. MATERIALS AND METHODS: Male Wistar rats were induced during one week with streptozotocin to develop Type 2 Diabetes (T2D) and then randomly distributed into four groups. T2D rats included in the first group received insulin glargine, the second group received NPH insulin, the third group received metformin; finally, untreated T2D rats were included as the control group. All groups were treated for seven days; after the treatment, tissue samples of liver and colon were obtained. Quantitative PCR (qPCR) was performed to analyze the Igf-1r, Insr and Igf-1 gene expression in each tissue sample. RESULTS: The liver tissue showed overexpression of the Insr and Igf-1r genes (P>0.001) in rats treated with insulin glargine in comparison with the control group. Similar results were observed for the Insr gene (P>0.011) in colonic tissue of rats treated with insulin glargine. CONCLUSION: These observations demonstrate that insulin glargine promote an excess of insulin and IGF-1 receptors in STZ-induced diabetic rats, which could overstimulate the mitogenic signaling pathways.

Different insulin concentrations in resuspended vs. unsuspended NPH insulin: Practical aspects of subcutaneous injection in patients with diabetes.

AIMS: This study measured the insulin concentration (Ins[C]) of NPH insulin in vials and cartridges from different companies after either resuspension (R+) or not (R-; in the clear/cloudy phases of unsuspended NPH). METHODS: Measurements included Ins[C] in NPH(R+) and in the clear/cloudy phases of NPH(R-), and the time needed to resuspend NPH and time for NPH(R+) to separate again into clear/cloudy parts. RESULTS: In vials of NPH(R+) (assumed to be 100%), Ins[C] in the clear phase of NPH(R-) was<1%, but 230±41% and 234±54% in the cloudy phases of Novo Nordisk and Eli Lilly NPH, respectively. Likewise, in pen cartridges, Ins[C] in the clear phase of NPH(R-) was<1%, but 182±33%, 204±22% and 229±62% in the cloudy phases of Novo, Lilly and Sanofi NPH. Time needed to resuspend NPH (spent in tipping) in vials was brief with both Novo (5±1s) and Lilly NPH (6±1s), but longer with all pen cartridges (50±8s, 40±6s and 30±4s from Novo, Lilly and Sanofi, respectively; P=0.022). Time required for 50% separation into cloudy and clear parts of NPH was longer with Novo (60±7min) vs. Lilly (18±3min) in vials (P=0.021), and affected by temperature, but not by the different diameter sizes of the vials. With pen cartridges, separation into clear and cloudy parts was significantly faster than in vials (P<0.01). CONCLUSION: Ins[C] in NPH preparations varies depending on their resuspension or not. Thus, subcutaneous injection of the same number of units of NPH in patients with diabetes may deliver different amounts of insulin depending on its prior NPH resuspension.

The clinical effectiveness of insulin glargine in patients with Type I diabetes in Brazil: findings and implications.

AIM: Published studies have challenged the cost-effectiveness of insulin glargine versus neutral protamine hagedorn (NPH) insulins in Brazil with limited evidence of increased effectiveness despite considerably higher acquisition costs. However, still a controversy. Consequently, there is a need to address this. MATERIALS & METHODS: Retrospective cohort study of Type I diabetes patients receiving insulin glargine in Brazil following NPH insulin who met the criteria. RESULTS: 580 patients were enrolled. HbA1c varied from 8.80 ± 1.98% in NPH insulin users to 8.54 ± 1.88% after insulin glargine for 6 months, which is not clinically significant. Frequency of glycemic control varied from 22.6% with NPH insulin to 26.2% with insulin glargine. No statistically significant difference was observed between controlled and still uncontrolled groups for all analyzed factors including type and frequency of insulin use and carbohydrate counting. CONCLUSION: Limited differences between NPH insulins and insulin analogs in routine clinical care do not justify an appreciable cost difference.

An RCT Investigating Patient-Driven Versus Physician-Driven Titration of BIAsp 30 in Patients with Type 2 Diabetes Uncontrolled Using NPH Insulin.

INTRODUCTION: The aim of this study was to confirm the efficacy of patient-driven titration of BIAsp 30 in terms of glycemic control, by comparing it to physician-driven titration of BIAsp 30, in patients with type 2 diabetes in North Africa, the Middle East, and Asia. METHODS: A 20-week, open-label, randomized, two-armed, parallel-group, multicenter study in Egypt, Indonesia, Morocco, Saudi Arabia, and Vietnam. Patients (n = 155) with type 2 diabetes inadequately controlled using neutral protamine Hagedorn (NPH) insulin were randomized to either patient-driven or physician-driven BIAsp 30 titration. RESULTS: The noninferiority of patient-driven compared to physician-driven titration with respect to the reduction in HbA1c was confirmed. The estimated mean change in HbA1c from baseline to week 20 was -1.27% in the patient-driven arm and -1.04% in the physician-driven arm, with an estimated treatment difference of -0.23% (95% confidence interval: -0.54; 0.08). After 20 weeks of treatment, the proportions of patients achieving the target of HbA1c <7.5% were similar between titration arms; the proportions of patients achieving the target of ≤6.5% were also similar. Both titration algorithms were well tolerated, and hypoglycemic episode rates were similar in both arms. CONCLUSION: Patient-driven titration of BIAsp 30 can be as effective and safe as physician-driven titration in non-Western populations. Overall, the switch from NPH insulin to BIAsp 30 was well tolerated in both titration arms and led to improved glycemic control. A limitation of the study was the relatively small number of patients recruited in each country. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT01589653. FUNDING: Novo Nordisk A/S, Denmark.

Insulins NPH, glargine, and detemir, and risk of severe hypoglycemia among working-age adults.

INTRODUCTION: The longer acting basal insulin analogs glargine and detemir have shown a lower incidence of hypoglycemia compared to insulin NPH in clinical studies. We evaluated the real-life risk of severe hypoglycemia among new users of insulins in the working-age population in Finland. METHODS: All persons aged 18-65 years with diabetes mellitus who were newly prescribed with insulins NPH, glargine, or detemir during 2006-2009, were identified from national registers. Risk of severe hypoglycemia requiring hospital care was compared between insulin types. RESULTS: A total of 16,985 persons initiated basal insulin treatment (5586, 7499, and 3900 patients started NPH, glargine, and detemir, respectively) during follow-up. Five hundred and thirty-six persons were hospitalized because of severe hypoglycemia. Absolute rate (per 1000 patient-years) was 20.6 (95% CI 17.9, 23.8), 17.8 (15.6, 20.3), and 12.4 (9.9, 15.5) for NPH, glargine, and detemir initiators, respectively. With NPH as reference, the adjusted hazard ratio (HR) was 0.92 (95% CI 0.74, 1.15, p = 0.47) for glargine, and 0.70 (0.51, 0.94, p= 0.018) for detemir. The HR for detemir compared to glargine was 0.76 (0.58, 0.99, p = 0.040). CONCLUSIONS: Initiating insulin treatment with detemir, but not with glargine, was associated with a significantly lower risk of severe hypoglycemia compared to NPH, among working-age adults. KEY MESSAGES The comparative safety of modern basal insulins regarding hypoglycemia among the working-age population is unclear. Large reductions in the incidence of severe hypoglycemia were seen among real-life patients who started insulin detemir, as compared to patients who initiated glargine or especially NPH insulin. Given the large amount of patients using insulin, these findings may have considerable clinical consequences at the population level.

Improved treatment satisfaction in patients with type 1 diabetes treated with insulin glargine 100U/mL versus neutral protamine Hagedorn insulin: An exploration of key predictors from two randomized controlled trials.

AIM: Investigate contributors to treatment satisfaction in type 1 diabetes (T1D). METHODS: Post-hoc analysis using the Diabetes Treatment Satisfaction Questionnaire status version (DTSQs) in 771 T1D patients from two 28-week trials comparing once-daily insulin glargine 100U/mL (Gla-100) with once- or twice-daily NPH neutral protamine Hagedorn (NPH) insulin. RESULTS: Gla-100 was associated with a significant improvement in treatment satisfaction versus NPH (overall population adjusted mean [standard error] DTSQs change from baseline: +1.13 [0.30] versus -0.04 [0.31]; p=0.006). In the overall population, treatment satisfaction improvement with all insulin regimens was related to less frequent severe hypoglycemia (coefficient-0.077; p=0.040) and HbA1c reduction (-0.066; p=0.082). By treatment regimen, relationships between treatment satisfaction and these outcomes approached or attained statistical significance for NPH insulin, but not Gla-100. In the overall population, predictors of treatment satisfaction improvement included: Gla-100 treatment (estimate 1.17, p=0.006), lower baseline DTSQs (-0.57, p<0.001), study (-1.01, p=0.019), lower severe hypoglycemia rate (0.17, p=0.012), and higher baseline HbA1c (0.44, p=0.014). By treatment regimen, these predictors remained significant for NPH insulin. CONCLUSIONS: Gla-100 resulted in a significant improvement in treatment satisfaction versus NPH insulin, independent of baseline disease characteristics and clinical outcomes.

Short and Long Term Effects of a DPP-4 Inhibitor Versus Bedtime NPH Insulin as ADD-ON Therapy in Patients with Type 2 Diabetes.

BACKGROUND: We conducted a comparison between the dipeptidyl-peptidase-4(DPP-4) inhibitor sitagliptin versus NPH insulin as an add-on therapies in patients with type 2 diabetes mellitus (T2D) failing oral medications. The objective was to ascertain the better indication in long-duration diabetes. METHODS: thirty-five T2D patients inadequately controlled with metformin plus glyburide were randomized to receive sitagliptin (n=18) or bedtime NPH insulin (n=17) for 12 months. HbA1c levels and a metabolic and hormonal profile at fasting and post-meal (every 30 minutes for 4 hours) were evaluated before and after 6 months (short-term) and 12 months (long-term) after adding sitagliptin or bedtime NPH insulin to their drug regime. RESULTS: Sitagliptin and NPH insulin decreased HbA1c levels equally after 6 months (p<0.001) with no further improvement after 12 months: sitagliptin (8.1±0.7% vs. 7.3±0.8% vs. 7.4±1.9%) and insulin (8.1±0.6% vs. 7.3±0.7% vs. 7.2±1.0%). Fasting glucose, fasting and postprandial triglyceride and C-peptide levels were also reduced by NPH insulin whereas postprandial insulin was decreased by sitagliptin. Body weight and postchallenge free fatty acid levels increased with insulin treatment. The transitory suppression (at 6 months) of postprandial proinsulin levels with both therapies, and of glucagon with sitagliptin, was followed by values similar or worse to those at pre-treatment. CONCLUSION: The use of either NPH insulin or a DPP-4 inhibitor as add-on treatments improves glucose control in patients with T2D failing on metformin plus glyburide therapy. The results were not attributed to a permanent improvement in alpha or beta cell function in patients with long-duration diabetes.

A randomised, open-labelstudy of insulin glargine or neutral protamine Hagedorn insulin in Chinese paediatric patients with type 1 diabetes mellitus.

BACKGROUND: We aimed to describe the safety and efficacy of insulin glargine in Chinese paediatric patients with type 1 diabetes mellitus (T1DM). Neutral protamine Hagedorn (NPH) insulin was the reference therapy. METHODS: This open-label, randomised, Phase III study was conducted at 10 sites in China. Children aged ≥6 to <18 years with T1DM were randomised (2:1) to insulin glargine or NPH insulin asbasal insulinfor a 24-week treatment period. For all patients, insulin aspart was given as bolus insulin. The primary endpoint was absolute change in glycated haemoglobin(HbA1c) from baseline to Week 24. Secondary endpoints included the percentage of patients reaching HbA1c <7.5% (<58.5 mmol/mol), and safety. The study was registered at clinicaltrials.gov (NCT01223131). RESULTS: In total,196 patients were screened, and 162 were randomised (107 and 55 patients were randomised to insulin glargine and NPH insulin, respectively). The mean ± SD of absolute change in HbA1c was-0.25 ± 1.68% (-2.69 ± 18.32 mmol/mol) in the insulin glargine group and -0.54 ± 1.67% (-5.55 ± 20.32 mmol/mol) in the NPH insulin group. At Week 24, 18.7 and 21.6% of patients in the insulin glargine and NPH insulin groups achieved HbA1c <7.5% (<58.5 mmol/mol). Both treatments were generally well tolerated. A numerically lower rate of symptomatic hypoglycaemia per patient year was observed for insulin glargine versus NPH insulin (24.3 ± 45.8 versus32.3 ± 43.2); severe hypoglycaemia was rare (<2%). CONCLUSIONS: Initiation of insulin glargine can aid Chinese paediatric patients with T1DM to safely reduce their HbA1c levels.

Comparative study between two recombinant human NPH insulin formulations for the treatment of type 2 diabetes mellitus

ABSTRACT Objective To compare the effects of the neutral protamine Hagedorn (NPH) recombinant human insulin formulations Gansulin and Humulin N® on the glycemic control of patients with type 2 diabetes mellitus (T2DM). Subjects and methods Prospective, double-blind, randomized, parallel, single-center study of 37 individuals with T2DM treated with NPH insulin formulations. The Tukey-Kramer test for multiple comparisons, the Wilcoxon paired comparison test and the Chi-Square test were used for the statistical analyses. The significance level was set at 5% (p < 0.05). Results The NPH insulin formulations Humulin and Gansulin similarly reduced the HbA1c levels observed at the end of the study compared with the values obtained at the beginning of the study. In the Humulin group, the initial HbA1c value of 7.91% was reduced to 6.56% (p < 0.001), whereas in the Gansulin group, the reduction was from 8.18% to 6.65% (p < 0.001). At the end of the study, there was no significant difference between the levels of glycated hemoglobin (p = 0.2410), fasting plasma glucose (FG; p = 0.9257) and bedtime plasma glucose (BG; p = 0.3906) between the two insulin formulations. There was no nt difference in the number of hypoglycemic events between the two insulin formulations, and no severe hyp episodes were recorded. Conclusion This study demonstrated similar glycemic control by NPH insulin Gansulin compared with human insulin Humulin N® in patients with T2DM.

Recombinant Human Insulins - Clinical Efficacy and Safety in Diabetes Therapy.

Insulin replacement therapy is the standard of care for patients with type 1 and advanced type 2 diabetes mellitus. Porcine and bovine pancreatic tissue was the source of the hormone for many years, followed by semisynthetic human insulin obtained by modification of animal insulin. With the development of recombinant DNA technology, recombinant (biosynthetic) human insulin became available in large amounts by biosynthesis in microorganisms (Escherichia coli, yeast) providing reliable supplies of the hormone worldwide at affordable costs. The purity and pharmaceutical quality of recombinant human insulin was demonstrated to be superior to animal and semisynthetic insulin and patients with diabetes could be safely and effectively transferred from animal or semisynthetic human insulin to recombinant human insulin with no change expected in insulin dose. The decision for change remains a clinical objective, follow-up after any change of insulin product is recommended to confirm clinical efficacy. This review provides a summary and retrospective assessment of early clinical studies with recombinant insulins (Insuman®, Humulin®, Novolin®).