Use Of Long-acting Insulin Analogues Research Articles

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.

Metabolic Impact of Frailty Changes Diabetes Trajectory

Diabetes mellitus prevalence increases with increasing age. In older people with diabetes, frailty is a newly emerging and significant complication. Frailty induces body composition changes that influence the metabolic state and affect diabetes trajectory. Frailty appears to have a wide metabolic spectrum, which can present with an anorexic malnourished phenotype and a sarcopenic obese phenotype. The sarcopenic obese phenotype individuals have significant loss of muscle mass and increased visceral fat. This phenotype is characterised by increased insulin resistance and a synergistic increase in the cardiovascular risk more than that induced by obesity or sarcopenia alone. Therefore, in this phenotype, the trajectory of diabetes is accelerated, which needs further intensification of hypoglycaemic therapy and a focus on cardiovascular risk reduction. Anorexic malnourished individuals have significant weight loss and reduced insulin resistance. In this phenotype, the trajectory of diabetes is decelerated, which needs deintensification of hypoglycaemic therapy and a focus on symptom control and quality of life. In the sarcopenic obese phenotype, the early use of sodium-glucose transporter-2 inhibitors and glucagon-like peptide-1 receptor agonists is reasonable due to their weight loss and cardio-renal protection properties. In the malnourished anorexic phenotype, the early use of long-acting insulin analogues is reasonable due to their weight gain and anabolic properties, regimen simplicity and the convenience of once-daily administration.

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.

Abstract 6919: Comparative Effectiveness of Long-Acting Insulin Analogs and Neutral Protamine Hagedorn (nph) Insulin for the Reduction of Major Adverse Cardiovascular Events Among Patients With Type 2 Diabetes

Introduction: Although long-acting insulin analogs (glargine, detemir, and degludec) and neutral protamine Hagedorn (NPH) insulin show similar efficacy for glycemic control among patients with type 2 diabetes, their comparative effectiveness in reducing cardiovascular events is unclear. Objective: To compare the risk of major adverse cardiovascular events (MACE) with the use of long-acting insulin analogs versus NPH among patients with type 2 diabetes. Methods: We conducted a retrospective cohort study using the Clinical Practice Research Datalink, a primary care database from the United Kingdom, linked with hospitalization and vital statistics data. The cohort included adults with type 2 diabetes initiating basal insulin therapy between 2002 and 2018. Exposure was defined as time-varying where each person-month of follow-up was classified as either current use of long-acting insulin analogs or NPH; patients who discontinued insulin treatment or were exposed to both insulin analogs and NPH in the same month were censored. The primary endpoint was MACE, a composite endpoint of myocardial infarction, ischemic stroke, and cardiovascular death. We used inverse probability of treatment and censoring weighting to estimate the adjusted hazard ratio (HR) and 95% confidence interval (CI) for MACE associated with current use of long-acting insulin analogs versus NPH. We also conducted secondary analyses stratified by age, sex, history of cardiovascular disease . Results: A total of 57,334 patients entered our cohort (31,136 using a long-acting analog and 26,198 using NPH. Mean age was 63.8 years, and 44.3% of patients were female. A total of 3,494 MACE events occurred over a mean follow-up of 1.62 years. Long-acting insulin analogs were not associated with a decreased risk of MACE compared to NPH (Table). Conclusions: Current use of long-acting insulin analogs is not associated with a reduced risk of MACE compared to use of NPH insulin among patients with type 2 diabetes.

Utilisation Trend of Long-Acting Insulin Analogues including Biosimilars across Europe: Findings and Implications.

Background Diabetes mellitus rates and associated costs continue to rise across Europe enhancing health authority focus on its management. The risk of complications is enhanced by poor glycaemic control, with long-acting insulin analogues developed to reduce hypoglycaemia and improve patient convenience. There are concerns though with their considerably higher costs, but moderated by reductions in complications and associated costs. Biosimilars can help further reduce costs. However, to date, price reductions for biosimilar insulin glargine appear limited. In addition, the originator company has switched promotional efforts to more concentrated patented formulations to reduce the impact of biosimilars. There are also concerns with different devices between the manufacturers. As a result, there is a need to assess current utilisation rates for insulins, especially long-acting insulin analogues and biosimilars, and the rationale for patterns seen, among multiple European countries to provide future direction. Methodology. Health authority databases are examined to assess utilisation and expenditure patterns for insulins, including biosimilar insulin glargine. Explanations for patterns seen were provided by senior-level personnel. Results Typically increasing use of long-acting insulin analogues across Europe including both Western and Central and Eastern European countries reflects perceived patient benefits despite higher prices. However, activities by the originator company to switch patients to more concentrated insulin glargine coupled with lowering prices towards biosimilars have limited biosimilar uptake, with biosimilars not currently launched in a minority of European countries. A number of activities were identified to address this. Enhancing the attractiveness of the biosimilar insulin market is essential to encourage other biosimilar manufacturers to enter the market as more long-acting insulin analogues lose their patents to benefit all key stakeholder groups. Conclusions There are concerns with the availability and use of insulin glargine biosimilars among European countries despite lower costs. This can be addressed.

Availability and Use of Long-Acting Insulin Analogues Including Their Biosimilars across Africa: Findings and Implications

Background: Prevalence rates of diabetes mellitus are growing across Africa with an appreciable number likely to be on insulin to manage their condition. This has significant implications on future morbidity and mortality exacerbated by high complication rates. Complication rates in patients requiring insulins are enhanced by hypoglycaemia. Long acting insulin analogues were developed to reduce hypoglycaemia and improve patient compliance. However, they are typically appreciably more expensive than human and other insulins in Africa, and continuing controversies surrounding their benefits limits their listing on national Essential Medicine Lists (EMLs). Biosimilars can reduce the prices long-acting insulin analogues. This needs assessing. Methods: Mixed methods approach including documentation of insulin utilisation patterns and prices among a range of African countries. In addition, input from senior level government, academic, and healthcare professionals from across Africa on the current situation with long-acting insulin analogues as well as potential changes needed to enhance future funding of long-acting analogue biosimilars. Results: There is variable listing of long-acting insulin analogues on national EMLs across Africa due to their high prices and issues of affordability. Even when listed, utilisation of long-acting insulin analogues is limited by similar issues including affordability. Appreciably lowering the prices of long-acting insulin analogues via biosimilars should enhance future listing on EMLs and use accompanied by educational and other initiatives. However, this will require increased competition to lower prices. Conclusion: There are concerns with value and funding of long-acting insulin analogues across Africa including biosimilars. A number of activities have been identified to improve future funding and listing on EMLs.

Current utilization patterns for long-acting insulin analogues including biosimilars among selected Asian countries and the implications for the future

Introduction Prevalence rates for diabetes mellitus continue to rise, which, coupled with increasing costs of complications, has appreciably increased expenditure in recent years. Poor glycaemic control including hypoglycaemia enhances complication rates and associated morbidity, mortality and costs. Consequently, this needs to be addressed. Whilst the majority of patients with diabetes have type-2 diabetes, a considerable number of patients with diabetes require insulin to help control their diabetes. Long-acting insulin analogues were developed to reduce hypoglycaemia associated with insulin and help improve adherence, which can be a concern. However, their considerably higher costs have impacted on their funding and use, especially in countries with affordability issues. Biosimilars can help reduce the costs of long-acting insulin analogues thereby increasing available choices. However, the availability and use of long-acting insulin analogues can be affected by limited price reductions versus originators and limited demand-side initiatives to encourage their use. Consequently, we wanted to assess current utilisation rates for long-acting insulin analogues, especially biosimilars, and the rationale for patterns seen, across multiple Asian countries ranging from Japan (high-income) to Pakistan (lower-income) to inform future strategies. Methodology Multiple approaches including assessing utilization and prices of insulins including biosimilars among six Asian countries and comparing the findings especially with other middle-income countries. Results Typically, there was increasing use of long-acting insulin analogues among the selected Asian countries. This was especially the case enhanced by biosimilars in Bangladesh, India, and Malaysia reflecting their perceived benefits. However, there was limited use in Pakistan due to issues of affordability similar to a number of African countries. The high use of biosimilars in Bangladesh, India and Malaysia was helped by issues of affordability and local production. The limited use of biosimilars in Japan and Korea reflects limited price reductions and demand-side initiatives similar to a number of European countries. Conclusions Increasing use of long-acting insulin analogues across countries is welcomed, adding to the range of insulins available, which increasingly includes biosimilars. A number of activities are needed to enhance the use of long-acting insulin analogue biosimilars in Japan, Korea and Pakistan.

The Current Situation Regarding Long-Acting Insulin Analogues Including Biosimilars Among African, Asian, European, and South American Countries; Findings and Implications for the Future.

Background: Diabetes mellitus rates continue to rise, which coupled with increasing costs of associated complications has appreciably increased global expenditure in recent years. The risk of complications are enhanced by poor glycaemic control including hypoglycaemia. Long-acting insulin analogues were developed to reduce hypoglycaemia and improve adherence. Their considerably higher costs though have impacted their funding and use. Biosimilars can help reduce medicine costs. However, their introduction has been affected by a number of factors. These include the originator company dropping its price as well as promoting patented higher strength 300 IU/ml insulin glargine. There can also be concerns with different devices between the manufacturers.Objective: To assess current utilisation rates for insulins, especially long-acting insulin analogues, and the rationale for patterns seen, across multiple countries to inform strategies to enhance future utilisation of long-acting insulin analogue biosimilars to benefit all key stakeholders.Our approach: Multiple approaches including assessing the utilisation, expenditure and prices of insulins, including biosimilar insulin glargine, across multiple continents and countries.Results: There was considerable variation in the use of long-acting insulin analogues as a percentage of all insulins prescribed and dispensed across countries and continents. This ranged from limited use of long-acting insulin analogues among African countries compared to routine funding and use across Europe in view of their perceived benefits. Increasing use was also seen among Asian countries including Bangladesh and India for similar reasons. However, concerns with costs and value limited their use across Africa, Brazil and Pakistan. There was though limited use of biosimilar insulin glargine 100 IU/ml compared with other recent biosimilars especially among European countries and Korea. This was principally driven by small price differences in reality between the originator and biosimilars coupled with increasing use of the patented 300 IU/ml formulation. A number of activities were identified to enhance future biosimilar use. These included only reimbursing biosimilar long-acting insulin analogues, introducing prescribing targets and increasing competition among manufacturers including stimulating local production.Conclusions: There are concerns with the availability and use of insulin glargine biosimilars despite lower costs. This can be addressed by multiple activities.

Utilization and expenditure on long-acting insulin analogs among selected middle-income countries with high patient co-payment levels: Findings and implications for the future

The number of patients with diabetes and associated complications is rising across countries including patients requiring insulin to control their diabetes. Hypoglycaemia combined generally with poor control adds to the burden of diabetes. Long-acting insulin analogues were developed to reduce hypoglycaemia, including nocturnal hypoglycaemia, and enhance adherence, which can be a problem. These benefits have resulted in increased use among high and high-middle income countries, which is continuing. However, concerns in middle and lower-income countries as insulin analogues are considerably more expensive than standard insulins. Biosimilars can reduce their costs. Consequently, important to ascertain current usage and prices of analogues across middle-income countries with high patient co-payment levels to provide future direction. Overall, limited use of insulin glargine in Kenya up to 3.6% of total insulins in one leasing hospital with prices up to 3.4 fold higher than standard insulins. Overall, limited use of insulin glargine among hospitals in Northern Nigeria and in pharmacies again due to high prices. Appreciably higher use of long-acting insulin analogues in Bangladesh enhanced by low cost biosimilars with increasing competition. Increased competition enhanced by local production can lower biosimilar costs enhancing future use of insulin glargine to the benefit of all diabetes patients requiring insulin.

The Use of Long-Acting Insulin Analogs and the Risk of Colorectal Cancer Among Patients with Type 2 Diabetes: A Population-Based Cohort Study.

The association between long-acting insulin analogs and colorectal cancer is uncertain, with previous studies reporting discrepant findings. To determine whether the use of long-acting insulin analogs is associated with an increased risk of colorectal cancer, when compared with use of intermediate-acting human insulins among patients with type 2 diabetes. We conducted a population-based study using the United Kingdom Clinical Practice Research Datalink (CPRD). We identified patients newly treated with either a long-acting insulin analog or an intermediate-acting human insulin between September 1, 2002 and January 31, 2018, with follow-up until January 31, 2019. Each long-acting insulin analog user was propensity score-matched to one intermediate-acting human insulin user, and a lag of 1year was imposed. Cox proportional hazards models were used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs) of colorectal cancer, comparing long-acting insulin analogs with intermediate-acting human insulin. Secondary analysis was conducted to assess whether there was a duration-response relationship. A total of 10,734 new long-acting insulin analog users were matched to 10,734 new intermediate-acting human insulin users. After a median follow-up of 2.8years, the use of long-acting insulin analogs was not associated with an increased risk of colorectal cancer, compared with intermediate-acting human insulin (1.80 vs. 1.87 per 1000 person-years, respectively; HR 0.96, 95% CI 0.70-1.34). There was no evidence of a duration-response relationship. The results of this population-based study indicate that use of long-acting insulin analogs is not associated with an overall increased risk of colorectal cancer.

VP53 Long-Acting Insulin Analogues In Brazil: Clinical And Economic Impact

IntroductionThe aim was to evaluate the effectiveness, safety and economic impact of long-acting insulin analogues (LAIA) compared to NPH for type 1 diabetes mellitus (DM1).MethodsA search was performed in five electronic databases to find systematic reviews (SR) comparing at least a LAIA to NPH insulin for DM1. Budget impact analysis was performed from the perspective of Brazilian public health system (SUS), with NPH insulin as the base scenario. The costs were extracted from the Integrated System of Administration of General Services (SIASG). The market share was calculated per month, using a logarithmic function with maximum diffusion of 50% at the end of the time horizon - five years.ResultsA total of 160 studies were identified and seven SR of low to uncertain risk of bias were selected. LAIA have shown modest clinical benefit and its effect is more prominent for the control of severe and nocturnal hypoglycaemia. Insulins glargine and detemir compared to NPH were associated with reduction in HbA1c levels between 0.16% and 0.40% and associated with lower risk of episodes of severe hypoglycemia. Insulin degludec compared to NPH showed no statistically significant difference in the reduction of HbA1c levels and in the episodes of severe hypoglycemia. The budget impact ranges from USD 210 million (detemir) to USD 670 million (degludec) over five years.ConclusionsThe use of LAIA as a basal insulin regimen for DM1 may benefit more patients with recurrent episodes of hypoglycemia. However, the fragility of the outcomes considered to evaluate the clinical impact of LAIA and the high budget impact with its use should be considered, and may compromise SUS sustainability. In view of these aspects, CONITEC recommended the incorporation of one of the LAIA, if the treatment is equal to or less than that of NPH insulin and according to the criteria established by a guideline.

Area Deprivation and Regional Disparities in Treatment and Outcome Quality of 29,284 Pediatric Patients With Type 1 Diabetes in Germany: A Cross-sectional Multicenter DPV Analysis.

This study analyzed whether area deprivation is associated with disparities in health care of pediatric type 1 diabetes in Germany. We selected patients <20 years of age with type 1 diabetes and German residence documented in the "diabetes patient follow-up" (Diabetes-Patienten-Verlaufsdokumentation [DPV]) registry for 2015/2016. Area deprivation was assessed by quintiles of the German Index of Multiple Deprivation (GIMD 2010) at the district level and was assigned to patients. To investigate associations between GIMD 2010 and indicators of diabetes care, we used multivariable regression models (linear, logistic, and Poisson) adjusting for sex, age, migration background, diabetes duration, and German federal state. We analyzed data from 29,284 patients. From the least to the most deprived quintile, use of continuous glucose monitoring systems (CGMS) decreased from 6.3 to 3.4% and use of long-acting insulin analogs from 80.8 to 64.3%, whereas use of rapid-acting insulin analogs increased from 74.7 to 79.0%; average HbA1c increased from 7.84 to 8.07% (62 to 65 mmol/mol), and the prevalence of overweight from 11.8 to 15.5%, but the rate of severe hypoglycemia decreased from 12.1 to 6.9 events/100 patient-years. Associations with other parameters showed a more complex pattern (use of continuous subcutaneous insulin infusion [CSII]) or were not significant. Area deprivation was associated not only with key outcomes in pediatric type 1 diabetes but also with treatment modalities. Our results show, in particular, that the access to CGMS and CSII could be improved in the most deprived regions in Germany.

PP44 Effectiveness Of Insulin Glargine Versus Detemir In Type 1 Diabetes

Introduction:The use of long-acting insulin analogues have been reported in patients with type 1 diabetes mellitus who exhibit important oscillations of their daily blood glucose, although the therapeutic benefits are lacking. The aim of this study was to evaluate the effectiveness and safety of the insulin analogue glargine compared detemir to support health decision-making.Methods:We performed a systematic review with meta-analysis of observational studies (cohort and registry), available in the MEDLINE (Pubmed), Latin American and Caribbean Health Sciences (LILACS), EMBASE and Cochrane Library databases (accessed August 2017), including research in the electronic journal Diabetes Care and gray literature. Several combinations of terms were used, including disease terms, interventions and type of study. The results evaluated were: glycated hemoglobin; weight gain; occurrence of severe hypoglycemia; total insulin dose; and, fasting capillary glycemia. Methodological quality was assessed using the Newcastle scale. The meta-analyses were performed in Review Manager® 5.2 software using a random effects model. Protocol number CRD42017054925 (International Prospective Register of Ongoing Systematic Reviews).Results:A total of 705 publications, eight cohort studies were included. The quality of included studies was classified as high. In the meta-analysis, the results for episodes of severe hypoglycemia (p = 0.002), measurements of fasting capillary glycemia (p = 0.01), and weight gain (p = 0.001) were favorable for detemir. The glycated hemoglobin endpoint (p = 0.49, heterogeneity = 89 percent) revealed high heterogeneity and no statistically significant difference between groups, showing no difference between the interventions for glycemic control.Conclusions:Although some results are favorable to detemir, it was not possible to identify significant differences in effectiveness and safety between the two analogues evaluated, requiring new long term studies and better quality of methodological studies.

Long-Term Use of Long-Acting Insulin Analogs and Breast Cancer Incidence in Women With Type 2 Diabetes.

Purpose The association between long-acting insulin analogs and increased breast cancer risk is uncertain, particularly with the short follow-up in previous studies. We assessed this risk long term in women with type 2 diabetes. Methods A population-based cohort of women 40 years or older, all of whom were treated with long-acting (glargine, detemir) or neutral protamine Hagedorn (NPH) insulin between 2002 and 2012, was formed using the United Kingdom's Clinical Practice Research Datalink. Women were followed until February 2015 or breast cancer diagnosis. Cox proportional hazards models were used to estimate adjusted hazard ratios (HRs) and 95% CIs of incident breast cancer, comparing long-acting insulin analogs with NPH overall, as well as by duration and cumulative dose. Results The cohort included 22,395 women who received insulin treatment, with 321 incident breast cancer events occurring during up to 12 years of follow-up (incidence rate 3.3 per 1,000 person-years). Compared with NPH insulin, insulin glargine was associated with an increased risk of breast cancer (HR, 1.44; 95% CI, 1.11 to 1.85), mainly increasing 5 years after glargine initiation (HR, 2.23; 95% CI, 1.32 to 3.77) and after > 30 prescriptions (HR, 2.29; 95% CI, 1.26 to 4.16). The risk was particularly elevated among prior insulin users (HR, 1.53; 95% CI, 1.10 to 2.12) but not for new users, which included fewer patients and for which one cannot rule out an HR of 1.81. The risk associated with insulin detemir was not significantly elevated (HR, 1.17; 95% CI, 0.77 to 1.77). Conclusion Long-term use of insulin glargine is associated with an increased risk of breast cancer in women with type 2 diabetes. The risk associated with insulin detemir remains uncertain because there are fewer users of this insulin.

Glycemic Control Rate in Patients With Type 1 Diabetes Treated at a Public Tertiary Referral Hospital in Rio de Janeiro, Brazil

Background: The incidence of type 1 diabetes (T1D) has been increasing worldwide, leading to a serious public health problem resulting in reduced life expectancy and increased morbidity. The aim of this study was to determine the glycemic control rate and its demographic and clinical factors, in T1D followed up at a tertiary referral hospital in Brazil. Methods: An observational and retrospective study was conducted between October 2014 and October 2015. Data were obtained from 140 medical records. Results: Satisfactory glycemic control rate was found in 22.14% of patients. There was no difference between the pediatric group and adult group regarding control rate. However, a worse HbA1C level was found in the pediatric group (P = 0.001). The use of long-acting insulin analogue (P = 0.03) was associated with satisfactory glycemic control, and a tendency was observed for both the combination of long-acting and ultra-rapid acting analogues (P = 0.08), and the absence of ketoacidosis during the course of diabetes (P = 0.08). In the group with satisfactory glycemic control, the median number of consultations (1 (1 - 4)) was significantly lower than in the uncontrolled group (2 (1 - 4)) (P = 0.003). Regarding the two major microvascular complications, 23.53% had retinopathy and 12.09% had nephropathy. Conclusions: The majority of patients did not obtain a satisfactory HbA1C level. Good glycemic control factors were directly associated with the use of long-acting insulin analogues, and the combination of long-acting and ultra-rapid analogues as well as the absence of ketoacidosis during T1D’s evolution tended also to be associated with better metabolic control. J Endocrinol Metab. 2016;6(5):135-142 doi: http://dx.doi.org/10.14740/jem369w

Insulin Analogues in the Treatment of Gestational Diabetes Mellitus

Rapid-acting insulin analogues are the preferred choice for short-acting insulin due to their superior pharmacologic profiles, leading to greater flexibility and convenience of dosing. This has lead to greater patient satisfaction and improved quality of life. Clinical experience with rapid-acting insulin analogues in pregnancy is increasing. Currently, there is limited data available on the use of long-acting insulin analogues in pregnancy. The focus of this review is to discuss the role of insulin analogue therapy in the treatment of the woman with gestational diabetes.

Management of diabetes mellitus: is the pump mightier than the pen?

Continuous subcutaneous insulin infusion (CSII, or insulin pump therapy) reduces HbA1c levels and hypoglycaemia in patients with type 1 diabetes mellitus (T1DM) compared with multiple daily insulin injections (MDI). The greatest reduction in HbA(1c) levels with CSII occurs in patients with the worst glycaemic control; therefore, the most appropriate and cost-effective use of CSII in adults with T1DM is in those who have continued, elevated HbA(1c) levels or disabling hypoglycaemic episodes with MDI (including the use of long-acting insulin analogues and structured patient education). The disadvantages of CSII include higher costs than MDI and the risk of ketosis in the event of pump failure. In children with T1DM, CSII may be used when MDI is considered impractical or inappropriate. Pumps are not generally recommended for patients with type 2 diabetes mellitus but may improve control in some subgroups. A new generation of smaller insulin infusion pumps with an integrated cannula, called patch pumps, could improve uptake of CSII in general. The important clinical question is not whether CSII is more efficacious than MDI in general adult T1DM, but whether CSII further improves glycaemic control when this control continues to be poor with MDI, and evidence exists that in most cases it does.

Incidence of malignancies in patients with diabetes mellitus and correlation with treatment modalities in a large Israeli health maintenance organization: a historical cohort study

It has been hypothesized that incidence of and mortality from several malignancies are increased among diabetic patients. Whether certain treatment modalities, including use of metformin, sulfonylureas, or insulins, affect cancer incidence or mortality and whether use of long-acting insulin analogues glargine and detemir may increase cancer incidence more than traditional human insulins are debated. The objective was to investigate the association between specific glucose-lowering agents and cancer incidence in diabetic members of an Israeli health maintenance organization. We studied a cohort of 36,342 diabetic patients aged at least 18 years with no history of cancer or treatment with insulin as of January 1, 2003. For the period from January 2003 to December 2007, we searched pharmacy records for purchases of glucose-lowering agents, including metformin, sulfonylureas, human insulin, and analogue insulins. Incident cancer diagnoses were identified from the health maintenance organization cancer registry. We studied the association of cancer incidence with the use of specific glucose-lowering agents, controlling for age, sex, and baseline glycohemoglobin measurement. Cancer was diagnosed in 6% of the study cohort during 164,652 person-years of follow-up time. Cancer incidence increased with age and varied with medication purchasing patterns. On multivariate analysis, age (hazard ratio [HR], 1.049; confidence interval [CI], 1.045-1.052), male sex (HR, 1.16; CI, 1.065-1.264), and number of insulin purchases (HR, 1.007; CI, 1.001-1.012) were significantly associated with increased cancer risk, whereas number of metformin purchases was associated with reduced cancer risk (HR, 0.996; CI, 0.994-0.998). Male sex, age, and human insulin purchases were associated with increased cancer incidence, whereas metformin purchases were associated with decreased cancer risk. There was a trend for increased cancer incidence associated with use of long-acting insulin analogues, but the number of long-acting insulin analogue users was too small for risk estimates to be conclusive.

PDB11 DRUG-USE PATTERNS OF INITIALLY PRESCRIBED INSULIN DETEMIR AND INSULIN GLARGINE IN THE NETHERLANDS;A COMPARATIVE ANALYSIS USING PHARMACY DATA FROM IADB. NL

OBJECTIVES: Newer long-acting insulin analogs have shown to result in several treatment improvements if compared with NPH insulins. Promising results from clinical trials require confirmation from observational settings reflecting potential “real-life” benefits. Therefore, the current study aimed to evaluate trends in prescribing (uptake), treatment adherence, and costs of (newer) insulin analogs (e.g., insulin detemir and insulin glargine). METHODS: A drug-utilization analysis was conducted based on using daily- practice prescription data from IADB.nl (one of the databases available in the Mondri- aan infrastructure), a dispensing database of 50 pharmacies, covering a Dutch population of 500,000. Drug-utilization data were collected for a 7-year period (2000-2007). All patients that received at least one prescription of an insulin analog-defined following the “Anatomical Therapeutical Classification” (ATC) as “A10A”-were included for this study. The prevalence and incidence of insulin use were both presented per 1000 population. Survival analysis was conducted to calculate the persistence on different insulin analogs. RESULTS: Preliminary results show a fast increase in the proportion of patients using the newer long-acting insulin analogs with 7% in 2003 to over 30% in 2006. Among patients initiating these newer insulin analogs, use of insulin glargine is more than two times higher compared to use of insulin detemir (507 vs. 190 starters in 2006). Patients that initiated treatment with long-acting insulin analogs were significantly more adherent to insulin glargine compared to insulin detemir (exact figures will be presented during the presentation). CONCLUSIONS: Current preliminary results show an increase in use of long-acting insulin analogs. Of these analogs, insulin glargine is most often initiated and seems to be well-received by patients. Further results will be presented based on a longer follow-up period including differences in HbAlc level dependent dosing and trends in cost development for insulin analogs over time. Also, the potential feature of “channelling” will be investigated.