Use Of Glargine Research Articles

Insulin Glargine and Cancer Risk: An Opinion Statement of the Endocrine and Metabolism Practice and Research Network of the American College of Clinical Pharmacy

Diabetes mellitus has reached epidemic proportions worldwide, eliciting extensive research on both the disease process and its treatment. Regardless of diabetes type, the progressive nature of the disease makes insulin the long-term mainstay of diabetes management. Recently, the insulin analog glargine was reported in several epidemiologic studies to be associated with an increased risk of cancer. Inconsistent study results and media attention have caused much angst and concern to health care professionals and the general population. A clear understanding of the current evidence is needed to adequately develop a patient-oriented risk:benefit assessment. Members of the Endocrine and Metabolism Practice and Research Network of the American College of Clinical Pharmacy evaluated available evidence to provide guidance and discussion on the risk of cancer with insulin glargine use. We believe the current link between insulin glargine and cancer is tenuous but merits further evaluation. An independent analysis of all available glargine clinical trial data should be performed, and a vigorous postmarketing safety study of glargine should be conducted. Until more substantial data are available, however, neither the choice of initial insulin therapy nor insulin maintenance regimens should be influenced by the current information linking insulin glargine to cancer.

Insulin glargine and NPH insulin increase to a similar degree epithelial cell proliferation and aberrant crypt foci formation in colons of diabetic mice.

The insulin analog glargine has a higher binding affinity than regular insulin for the insulin-like growth factor 1 receptor in vitro, raising questions about increased mitogenicity in vivo. Observational studies in humans have recently reported a potential differential association between insulin glargine and malignancies, but available evidence remains inconclusive. We directly compared glargine vs. neutral protamine Hagedorn (NPH) insulin's effects on cell proliferation in colonic mucosa and on formation of aberrant crypt foci in diabetic mice, i.e., early stages of colorectal cancer development. Mice (BKS.Cg-+Lepr(db)/+Lepr(db)/OlaHsd) were treated with insulin glargine (G), NPH insulin (NPH), or saline (NaCl). We assessed epithelial proliferation after long-term insulin treatment (18 weeks) by 5-bromo-2'-deoxyuridine and Ki67 staining and analyzed the formation of aberrant crypt foci (ACF) in mice treated with insulin glargine or NPH insulin or 10 weeks after initiation with 1,2-dimethylhydrazine. Insulin glargine treatment did not result in significantly different epithelial colonic proliferation compared to NPH insulin (G, 137 ± 22; NPH, 136 ± 15; NaCl, 100 ± 20 (relative proliferation index)), but both insulin-treated groups of mice had a higher proliferation index compared to the NaCl control group (p<0.001). Similarly, we observed no difference in ACF formation between glargine- and NPH-insulin-treated mice (G, 132 ± 12; NPH, 138 ± 9; NaCl, 100 ± 7 (relative number of ACF)), but ACF formation was significantly higher in insulin-treated mice than in NaCl-treated control mice (p=0.001). Chronic insulin treatment results in higher colonic epithelial proliferation and ACF formation, but the use of insulin glargine vs. NPH insulin is not associated with increased risk.

Glargine vs. NPH insulin therapy in pregnancies complicated by diabetes: An observational cohort study

Aims The effects of glargine insulin therapy in pregnancies are not well established. We compared maternal and neonatal outcomes of women with pregestational and gestational diabetes treated with glargine or NPH insulin. Methods A prospective cohort study was conducted analyzing outcomes from 56 women with pregestational and 82 with gestational diabetes treated with either insulin regimen. Results Comparisons were performed among 138 women: 56 with pregestational and 82 with gestational diabetes. In relation to maternal complications, worsening of retinopathy and nephropathy, preeclampsia, micro and macroalbuminuria, and all kinds of hypoglycemia were found higher in women with pregestational diabetes NPH-treated vs. glargine-treated. In women with gestational diabetes NPH-treated, it was observed increased incidence of prepregnancy and new-onset pregnancy hypertension, micro and macroalbuminuria, as well as mild and frequent hypoglycemia, compared to glargine-treated. Among the neonatal outcomes, 1-min Apgar score <7, necessity of intensive care unit and fetal death in pregestational, while jaundice and congenital malformations in gestational diabetes, respectively, were more frequently observed in infants born to NPH-treated, compared to glargine-treated. Conclusions Glargine use during pregnancy from preconception through delivery, showed to be safe since it is associated with decreased maternal and neonatal adverse outcomes compared with NPH insulin-treated patients.

Insulin glargine does not increase the risk of malignancy.Synopsis of the article ?Combined randomised controlled trial experience of malignancies in studies using insulin glargine?byHome P.D. &amp;amp; Lagarenne P. (Diabetologia 2009, vol. 52 (12): 2499-2506)

Results of 31 controlled randomized studies of insulin glargine given to patients with diabetes mellitus are reviewed to evaluate the frequency of malignantneoplasms. 52 tumours were diagnosed in 45 (0.8%) patients on insulin glargine therapy and 48 tumors in 46 (0.9%) patients using other insulins(mostly NPX insulin). The incidence of breast cancer was equal (0.1%) in both groups (4 and 6 cases respectively). These data indicate thatthe use of insuline glargine does not increase the risk of malignancy, e.g. breast cancer.

Use of insulin glargine throughout pregnancy in 102 women with type 1 diabetes

Aim The aim of this study was to examine the safety of insulin glargine during pregnancy in women with type 1 diabetes mellitus (T1DM). Methods This retrospective multicentre study involved women with T1DM treated with insulin glargine before conception and throughout pregnancy. The main investigated parameters were HbA 1c during the first and third trimesters, major congenital malformations, and perinatal mortality and complications. Results For the 102 women with T1DM in the study, HbA 1c during the first and third trimesters was 6.7 ± 1.2% (95% CI 6.4–6.9%) and 6.2 ± 0.9% (95% CI 6.0–6.4%), respectively. Two congenital malformations (2%) were reported, and one stillbirth (1%) occurred at week 35 of gestation. The rate of preterm delivery was 23%. The mean birth weight was 3381 ± 595 g (95% CI 3255–3506 g), and the proportion of large-for-gestational-age infants was 30%. Conclusion Insulin glargine use throughout pregnancy does not appear to be associated with an increased rate of severe congenital malformations.

Long-Acting Insulin Analogs and the Risk of Diabetic Ketoacidosis in Children and Adolescents With Type 1 Diabetes

OBJECTIVETo investigate if long-acting insulin analogs decrease the risk of diabetic ketoacidosis (DKA) in young individuals with type 1 diabetes.RESEARCH DESIGN AND METHODSOf 48,110 type 1 diabetic patients prospectively studied between 2001 and 2008, the incidence of DKA requiring hospitalization was analyzed in 10,682 individuals aged ≤20 years with a diabetes duration of ≥2 years.RESULTSThe overall rate of DKA was 5.1 (SE ± 0.2)/100 patient-years. Patients using insulin glargine or detemir (n = 5,317) had a higher DKA incidence than individuals using NPH insulin (n = 5,365, 6.6 ± 0.4 vs. 3.6 ± 0.3, P < 0.001). The risk for DKA remained significantly different after adjustment for age at diabetes onset, diabetes duration, A1C, insulin dose, sex, and migration background (P = 0.015, odds ratio 1.357 [1.062–1.734]).CONCLUSIONSDespite their long-acting pharmacokinetics, the use of insulin glargine or detemir is not associated with a lower incidence of DKA compared with NPH insulin.

Insufficient evaluation of adverse events is not a proof of safety. Reply to LG Hemkens, U Grouven, R Bender, et al. [letter

Insufficient evaluation of adverse events is not a proof of safety. Reply to LG Hemkens, U Grouven, R Bender, et al. [letter

Lipoatrophy associated with the use of insulin analogues: a new case associated with the use of insulin glargine and review of the literature

Importance of the field: Any insulin formulation can in principle cause lipoatrophy; even cases associated with recombinant human insulin have been reported. An increasing number of case reports have been published indicating that lipoatrophy also develops after treatment with various insulin analogues.Areas covered in this review: In this review, we summarise the literature on lipoatrophy associated with the use of insulin analogues published to date. A new case of lipoatrophy associated with the use of glargine is presented.What the reader will gain: Readers will gain insight into: i) pathogenesis of lipoatrophy associated with the use of insulin analogues and ii) clinical features of lipoatrophy.Take home message: Twelve cases with lipoatrophy under treatment with insulin analogues have been reported so far. The exclusive occurrence in lean type 1 diabetic patients, its overlap with further autoimmune diseases and the overrepresentation of female individuals point to an immune pathogenesis. The respective exposition to the analogues lispro, aspart, glargine and detemir prior to lipoatrophy development varied considerably between 4 weeks and 2 years. No spontaneous substantial recovery of lipoatrophic areas has been reported. Frequent use of the same pen needle and lack of rotating of insulin injection sites seem to favour the development of lipoatrophy.

A comparison of costs among patients with type 2 diabetes mellitus who initiated therapy with exenatide or insulin glargine

Exenatide (Byetta) and insulin glargine (Lantus) are antidiabetic agents that are typically used after lack of response to an oral antidiabetic agent(s). Although previous research has examined the impact of these medications on glycaemic control, there is little information about the relative costs associated with the medications. To compare costs among patients with type 2 diabetes mellitus treated with exenatide or insulin glargine from a US third-party payer perspective. Data from a large, national administrative claims database were used in this study. The intent-to-treat (ITT) cohort included adults who were diagnosed with type 2 diabetes and initiated therapy with either exenatide (n = 4090) or insulin glargine (n = 1660). In addition, included patients were required to have no diagnoses of type 1 diabetes, to have received at least two prescriptions for an oral antidiabetic agent in the 6 months prior to first use of either exenatide or insulin glargine and to have continuous insurance coverage from 6 months before, to 12 months after, initiation on ITT medication. Annual total medical costs and total diabetes-related medical costs, in $US, year 2007 values, were estimated using stepwise multivariate regressions. Major cost components were also examined using either stepwise multivariate regressions or a two-part model that controlled for the probability of using the service. Smearing estimates were used to transform estimated log costs into costs. The analysis controlled for the potential impact of patient demographics, general health, prior resource use, co-morbidities and complications, and timing of treatment initiation. Compared with insulin glargine, initiation of exenatide was associated with significantly lower total direct medical costs ($US19,293 vs $US23,782; p < 0.0001), inpatient costs ($US4121 vs $US7532; p < 0.0001), outpatient costs ($US9501 vs $US12,885; p < 0.0001), emergency department (ED) costs ($US82 vs $US131; p < 0.0001), total diabetes-related medical costs ($US7833 vs $US8536; p < 0.0001), diabetes-related inpatient costs ($US2172 vs $US3538; p < 0.0001) and diabetes-related outpatient costs ($US2739 vs $US3249; p < 0.0001). Initiation of exenatide was associated with significantly higher total overall drug costs ($US6885 vs $US5936; p < 0.0001) and diabetes-related drug costs ($US3160 vs $US2422; p < 0.0001). Compared with the use of insulin glargine, use of exenatide was associated with significantly lower annual total direct medical costs and significantly lower total diabetes-related medical costs, despite higher total drug costs and higher diabetes-related drug costs. In addition, exenatide was associated with significantly lower total inpatient, outpatient, ED, and diabetes-related inpatient and outpatient costs.

Putting Insulin Glargine and Malignancies into Perspective

This paper examines publications on the risk for cancer of patients with type 2 diabetes and the use of insulin glargine.

ABCD response to possible link between risk of cancer and use of insulin glargine

Practical Diabetes InternationalVolume 26, Issue 7 p. 260-260 Position StatementFree Access ABCD response to possible link between risk of cancer and use of insulin glargine First published: 02 September 2009 https://doi.org/10.1002/pdi.1390AboutSectionsPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat In July this year, four studies were published on the website of the journal Diabetologia, a highly respected peer reviewed scientific journal, which raise possible concern about an increased risk of diagnosis of cancer in people with diabetes using the long-acting insulin glargine (Lantus).1 Glargine is the most widely used long-acting insulin in the UK and has been available for almost 10 years. It has been of benefit to many patients, particularly those at risk of overnight hypoglycaemia. In the largest study from a German health insurance registry, although there was no increased risk of cancer associated with Lantus compared to other insulins, when the data were adjusted for dose there was a modest association with overall risk of a diagnosis of cancer, when Lantus was the only insulin prescribed. A study performed in Sweden demonstrated no increase in overall risk of diagnosis of cancer, but there was an increased risk of diagnosis for breast cancer associated with Lantus insulin used alone. Two further studies performed in the UK did not confirm these results. Interpretation of these studies is complicated by confounding factors such as the type of older patient with type 2 diabetes who would be treated with glargine alone. The studies were based on reviews of case records recording diabetes treatment and development of cancer. All of the reports are observational epidemiological studies, which can only examine relationships and are unable to show cause and effect. They must be seen in this respect and considered inconclusive, not least given differing results. An extensive and thoughtful editorial reflected on the importance of the issue as the suggested link between glargine and progression of cancer was plausible. A firm statement was made that there was no evidence from this research of any harm from glargine in type 1 diabetes, in men generally, or showing any association with premenopausal breast cancer. The Association of British Clinical Diabetologists (ABCD) notes the comments of the European Medicines Agency (EMEA),2 and supports their investigation into this issue. ABCD also urges the international diabetes research community urgently to work with the regulatory authorities to determine what further studies are needed to clarify this issue because of the concern that will be felt by people with diabetes and by the specialists caring for them. The EMEA states that: 'On the basis of the currently available data, a relationship between insulin glargine and cancer cannot be confirmed nor excluded. However, the concerns raised by the four studies require further in-depth evaluation… ‘Patients being treated with insulin glargine are advised to continue their treatment as normal. At this time there is no recommendation that patients should change their current treatment. In case of any concerns, patients should consult their doctor.’ At the present time, ABCD does not recommend that people using glargine (Lantus) change to another long-acting insulin, but where people are concerned about the risk—and may wish to change their insulin—that they have the opportunity to discuss the situation with a diabetes specialist. Warn patients not to stop their insulin. References 1http://webcast.easd.org:80/press/glargine/glargine.htm. Google Scholar 2www.emea.europa.eu/humandocs/PDFs/EPAR/Lantus/40847409en.pdf. Google Scholar Volume26, Issue7September 2009Pages 260-260 ReferencesRelatedInformation

Insulin treatment in children and adolescents with diabetes

Department of Pediatrics, Uddevalla Hospital, Uddevalla,SwedenCorresponding author:Hans-Jacob Bangstad, MDDepartment of PaediatricsOslo University HospitalUlleval˚Kirkeveien 166Oslo N-0407Norway.Tel: 0047-22118765;fax: 0047-22118663;e-mail: haba@uus.noConflicts of interest: RH has received lecture honoraria fromNovo Nordisk, Lilly, Sanofi-Aventis, Medtronic and Roche. PJ-Chas received lecture fees from Eli Lilly, Novo-Nordisk, Sanofi-Aventis, Abbott, Bayer, Medtronic and Roche.The remainingauthors have declared no potential conflicts.Editors of the ISPAD Clinical Practice Consensus Guide-lines 2009 Compendium: Ragnar Hanas, Kim Donaghue,Georgeanna Klingensmith, and Peter Swift.This article is a chapter in the

Similar progression of diabetic retinopathy with insulin glargine and neutral protamine Hagedorn (NPH) insulin in patients with type 2 diabetes: a long-term, randomised, open-label study. Reply to Chantelau E [letter] and Currie CJ [letter

Similar progression of diabetic retinopathy with insulin glargine and neutral protamine Hagedorn (NPH) insulin in patients with type 2 diabetes: a long-term, randomised, open-label study. Reply to Chantelau E [letter] and Currie CJ [letter

Utilização da insulina glargina em crianças menores de oito anos de idade

To evaluate prospectively the efficacy and safety of insulin glargine use for the metabolic control of type 1 diabetes mellitus (T1DM) children younger than eight years old. Nineteen boys and 11 girls with T1DM were included. Before initiating insulin glargine, all children received intensive NPH and aspart insulins for three months. Afterwards, they were assisted for 12 more months for glargine treatment. All patients performed self blood glucose monitoring before and two hours after meals and in early morning (3:00 AM). Primary endpoints: metabolic control using A1C levels; frequency of mild hypoglycemia (capillary glycemia < 60 mg/dL); and frequency of severe hypoglycemia (loss or alteration of consciousness, seizures or need for medical intervention). Mean A1C at the study entry was 8.68% and after 12 months of glargine, was 8.64% (p = 0.82). Frequency of mild hypoglycemia at 3.00 AM was 1.43/3 months during the NPH period and 0.28/3 months during the glargine period (p < 0.007). Frequency of severe hypoglycemia was 0.56/3 months during the NPH period and 0.008/3 months during the glargine period (p < 0.002). The treatment of T1DM children with insulin glargine was considered as efficacious as with NPH. However, a better safety profile, disclosed by the lower incidence of nocturnal and severe hypoglycemia episodes, was observed for insulin glargine.

Insulin glargine and malignancy: an unwarranted alarm

Insulin glargine is a recombinant insulin analogue that has become widely used, largely because of a lower risk of hypoglycaemia and prolonged stable action. Synthetic insulins differ from human insulins in both metabolic and cell-growth activities, which raises legitimate concerns about risk of malignancy. 1 Smith U Gale EAM Does diabetes therapy influence the risk of cancer?. Diabetologia. 2009; (published online.)https://doi.org/10.1007/s00125-009-1441-5 Crossref Scopus (284) Google Scholar A recent observational study claimed an increased cancer incidence in people using glargine insulin compared with other human insulins, but this effect was only apparent after adjusting for dose. 2 Hemkens LG Grouven U Bender R et al. Risk of malignancies in patients with diabetes treated with human insulin or insulin analogues: a cohort study. Diabetologia. 2009; (published online June 30.)https://doi.org/10.1007/s00125-009-1418-4 Crossref Scopus (528) Google Scholar Subsequently, three further observational studies 3 Currie CJ Poole CD Gale EA The influence of glucose-lowering therapies on cancer risk in type 2 diabetes. Diabetologia. 2009; (published online July 2.)https://doi.org/10.1007/s00125-009-1440-6 Crossref Scopus (956) Google Scholar , 4 Jonasson JM Ljung R Talbäck M Haglund B Gudbjörnsdòttir S Steineck G Insulin glargine use and short-term incidence of malignancies—a population-based follow-up study in Sweden. Diabetologia. 2009; (published online.)https://doi.org/10.1007/s00125-009-1444-2 Crossref PubMed Scopus (371) Google Scholar , 5 SDRN Epidemiology GroupUse of insulin glargine and cancer incidence in Scotland: a study from the Scottish Diabetes Research Network Epidemiology Group. http://webcast.easd.org/press/glargine/download/090818Colhounacceptedpaperadjusted.pdf Google Scholar and one randomised trial 6 Rosenstock J Fonseca V McGill JB et al. Similar risk of malignancy with insulin glargine and neutral protamine Hagedorn (NPH) insulin in patients with type 2 diabetes: findings from a 5 year randomised, open-label study. Diabetologia. 2009; (published online.)https://doi.org/10.1007/s00125-009-1452-2 Crossref Scopus (129) Google Scholar have investigated whether insulin glargine is associated with cancer incidence. Insulin glargine and cancer: another side to the story?In their Comment (Aug 15, p 511),1 Stuart Pocock and Liam Smeeth review four papers2–5 and an editorial6 in Diabetologia, which raise concern about the possibility that insulin glargine might increase the risk of cancer, and declare that there is no conclusive evidence of this. They go on to remark that “claims of harm not backed by adequate evidence can provoke unnecessary alarms and anxieties”. Coming as it does from one of the iconic figures in medical statistics, this statement implies that the journal I edit has acted in an irresponsible and alarmist manner. Full-Text PDF

Use of insulin glargine and cancer incidence in Scotland: a study from the Scottish Diabetes Research Network Epidemiology Group

Aims/hypothesisThe aim of the present study was to examine whether patients with diabetes in Scotland using insulin glargine have a greater cancer risk than patients using other types of insulin.MethodsWe used a nationwide diabetes clinical database that covers the majority of the Scottish population with diagnosed diabetes, and examined patients with diabetes who were exposed to any insulin therapy between 1 January 2002 and 31 December 2005. Among these we defined a fixed cohort based on exposure during a 4 month period in 2003 (n = 36,254, in whom 715 cases of cancer occurred) and a cohort of new insulin users across the period (n = 12,852 in whom 381 cancers occurred). Records from these cohorts were linked to cancer registry data up to the end of 2005. We used Cox proportional hazards models for survival analyses.ResultsThose receiving any insulin glargine (n = 3,959) had the same incidence rate for all cancers as those not receiving insulin glargine (HR 1.02, 95% CI 0.77–1.36, p = 0.9 in the fixed cohort) The subset of patients using insulin glargine alone (n = 447) had a significantly higher incidence of all cancers than those using other insulins only (n = 32,295) (HR 1.55, 95% CI 1.01–2.37, p = 0.045), and those using insulin glargine with other insulins (n = 3,512) had a slightly lower incidence (HR 0.81, 95% CI 0.55–1.18, p = 0.26). There were important differences in baseline characteristics between these three groups, although the risk ratios were broadly unaltered on adjustment for these. Overall, there was no increase in breast cancer rates associated with insulin glargine use (HR 1.49, 95% CI 0.79–2.83, though insulin glargine only users had a higher rate than those using non-glargine insulin only (HR 3.39, 95% CI 1.46–7.85, p = 0.004). Among type 2 diabetic incident insulin users, no significant difference between the three groups was observed with respect to all cancer or breast cancer. All the above HRs are adjusted for age, calendar time prior cancer and type of diabetes, as appropriate, and are stratified according to sex.Conclusions/interpretationOverall, insulin glargine use was not associated with an increased risk of all cancers or site-specific cancers in Scotland over a 4 year time frame. Given the overall data, we consider the excess of cases of all cancers and breast cancer in the subgroup of insulin glargine only users to more likely reflect allocation bias rather than an effect of insulin glargine itself.Electronic supplementary materialThe online version of this article (doi:10.1007/s00125-009-1453-1) contains supplementary material, which is available to authorised users.

Insulin glargine use and short-term incidence of malignancies—a population-based follow-up study in Sweden

In the light of a report suggesting that insulin glargine may increase cancer occurrence, the EASD asked us to perform this study. We followed 114,841 individuals who had a prescription dispensed for insulin between 1 July and 31 December 2005. From 1 January 2006 to 31 December 2007, we noted the occurrence of malignancies. Seven different nationwide registers were used to obtain information on insulin exposure, outcome and possible confounders; these were linked using the unique personal identity number assigned to every Swedish resident. After adjustment for age and, when appropriate, sex, users of insulin glargine alone (no other types of insulin), compared with users of types of insulin other than insulin glargine, had an RR of 1.99 (95% CI 1.31-3.03) for breast cancer, 0.93 (95% CI 0.61-1.40) for gastrointestinal cancer, 1.27 (95% CI 0.89-1.82) for prostate cancer and 1.07 (95% CI 0.91-1.27) for any type of malignancy. Adjustment for age, smoking, BMI, age at onset of diabetes, age at birth of first child, cardiovascular disease and oestrogen use gave an RR for breast cancer of 1.97 (95% CI 1.29-3.00). The 95% CIs crossed 1.0 for the RR calculated in all analyses of users of insulin glargine in combination with other types of insulin. In Sweden, during 2006 and 2007, women using insulin glargine alone (no other types of insulin) had an increased incidence rate of breast cancer as compared with women using types of insulin other than insulin glargine. This result may be due to a random fluctuation; the possibilities for examining validity are limited, and no statistically significant results were obtained for any other individual cancer site or for the outcome 'all malignancies'. No definitive conclusions regarding a possible causal relationship between insulin glargine use and the occurrence of malignancies can be drawn from the results of this study.

Perinatal Outcomes in Pregnancies Managed with Antenatal Insulin Glargine

We compared perinatal outcomes in pregnancies in which insulin glargine was used in the management of patients with pregnancies in which standard insulin therapy was used at a single institution. A retrospective analysis of 114 pregnant patients with diabetes (pregestational or gestational) managed at a single center between January 2004 and August 2006 was undertaken. Sixty-five patients managed with insulin glargine were compared with 49 patients managed with neutral protamine Hagedorn (NPH) insulin. Both groups were also treated with short-acting insulin (either regular, lispro, or aspart insulin). Maternal age, parity, prepregnancy weight, body mass index, duration of diabetes, hemoglobin A (1C) (at entry and final recorded) and gestational age at entry were similar for each group (glargine and NPH). Thirty patients had gestational diabetes (18 glargine and 12 NPH); there were no differences in numbers of patients in higher-order White's classification between the two groups. Cesarean section for obstetric reasons included labor abnormalities, malpresentation, fetal distress, and suspected macrosomia. There were no differences in gestational age at delivery, birth weight, preeclampsia, or frequency of cesarean section (total or for obstetric reasons). The frequency of shoulder dystocia was higher in the NPH group. Regarding neonatal outcomes, gestational age at delivery, birth weight, Apgar scores, admission to the neonatal intensive care unit, respiratory distress syndrome, hypoglycemia, and congenital anomalies were similar between the two groups. From this retrospective analysis, no adverse maternal or neonatal effects were seen from maternal administration of insulin glargine. A larger multicenter study is needed to confirm these findings. This preliminary report suggests that use of insulin glargine during pregnancy can be considered if maternal metabolic control is suboptimal using the standard split-mix regimen.

Incidence rates of heart failure, stroke, and acute myocardial infarction among Type 2 diabetic patients using insulin glargine and other insulin

The aim of this study was to compare incidence rates of heart failure, stroke, and acute myocardial infarction (AMI) in Type 2 diabetic patients using different types of insulin. Included were patients with a diagnosis of Type 2 diabetes and at least one insulin prescription from May 2001 to July 2007. Incidence rate ratios (RRs) of heart failure, stroke, and AMI were estimated using Poisson regression with adjustment for age, gender, history of hypertension, dyslipidemia history, days supply, and duration of diabetes. Incidence rates of heart failure, stroke, and AMI in the insulin glargine group were 306.9 (95%CI: [278.9, 334.8]), 174.8 (95%CI: [153.7, 195.8]), and 105.2 (95%CI: [88.9, 121.5]) cases per 10,000 person-years, respectively. After adjustment for covariates, the incidence rates of CVD events in the insulin glargine were comparable to those in the other long/intermediate acting insulin group (reference), except for AMI, which tended to be lower in the insulin glargine group (RR = 0.81, 95%CI: [0.65, 1.02]). Using the same reference, the incidence rate of stroke was higher in patients taking rapid/short acting insulin, premixed insulin, or mixed use of insulin except insulin glargine (RR = 1.20, 95%CI: [1.04, 1.40]). This study suggested that insulin glargine use might be associated with a lower risk of AMI, compared to the other long/intermediate acting insulin use, and that insulin regimen of rapid/short acting insulin, premixed insulin, or mixed use of insulin except insulin glargine was associated with a higher risk of stroke using the same reference.

Insulin Glargine: a review 8 years after its introduction

Insulin Glargine was the first long-acting insulin analog produced by recombinant DNA technology, approved for use by the US FDA in April 2000 and by the European Agency for the Evaluation of Medicinal Products in June, 2000. It has become the most widely used insulin in the USA owing to its long duration of action without a pronounced peak. The principal advantage of insulin Glargine over neutral protamine Hagedorn (NPH) insulin is in a lower frequency of hypoglycemic reactions, thus affording improved safety. It is used in both type 1 and type 2 diabetes, usually as a single daily dose. In type 2 patients, it is often the first insulin introduced as a single daily dose. Although insulin Glargine is typically administered as a single nighttime dose, it can be given in the morning or at any other time convenient for the patient. In labile type 1 diabetes, it is often most effective given as two daily injections. In obese, insulin-resistant patients, it may be best to administer insulin Glargine in two separate doses, owing to the high volumes of injected insulin required. Insulin Glargine does not treat postprandial hyperglycemia. It is necessary to supplement with short-acting insulin at mealtimes to control glucose surges after meals. Insulin Glargine is effective in hospitalized and postsurgical patients on account of its lack of pronounced insulin peaks and long duration of action. Although there is considerable use of Glargine in pregnant diabetic women, there is no definitive study to confirm its benefits. Insulin Glargine is thought to coprecipitate supplementary short-acting insulins when co-administered in the same syringe. Therefore, more injections are typically needed in the usual treatment regimen for insulin requiring diabetes. In many cases, constant basal insulin levels may be achieved with multiple overlapping doses of NPH insulin given together with short-acting insulin at mealtimes. Such a therapy may be less costly, but the major advantage of insulin Glargine remains the greater safety of a lower frequency of hypoglycemic reactions.