Safety of Insulin Glargine Use in Pregnancy

8/12/2019 Safety of Insulin Glargine Use in Pregnancy

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Safety of Insulin Glargine Use in Pregnancy A Systematic Review and Meta-analysis

Erika Pollex, PhD PhD Graduate, Myla E Moretti, MSc, Gideon Koren, MD FRCPC,Denice S Feig, MD FRCPC

The Annals of Pharmacotherapy. 2011;45(1):1-8.

Abstract and IntroductionAbstract

Background: The prevalence of diabetes in women of childbearing age isincreasing. As such, the number of pregnancies complicated by diabetes willinevitably increase. New insulin analogues such as the long-acting analogue insulinglargine may represent beneficial treatment options in pregnancy by ensuring that

patients achieve excellent glycemic control without risk of maternal hypoglycemia.

Objective: To determine the fetal safety of insulin glargine use in the treatment ofdiabetes in pregnancy compared with NPH insulin therapy.

Methods: A systematic review and meta-analysis was performed of all originalhuman studies that reported neonatal outcomes among women with pregestationalor gestational diabetes who were managed with either insulin glargine or NPHinsulin during pregnancy. A systematic literature search was conducted usingMEDLINE, EMBASE, CINAHL, the Cochrane Central Register for Controlled Trials

database, and Web of Science from 1980 to June 1, 2010. Outcomes included largesize for gestational age, macrosomia, neonatal hypoglycemia, neonatal intensivecare unit admissions, birth trauma, congenital anomalies, preterm delivery, perinatalmortality, respiratory distress, and hyperbilirubinemia. Relative risk ratios andweighted mean differences were computed with 95% confidence intervals.

Results: Eight studies reporting on a total of 702 women with pregestational orgestational diabetes in pregnancy treated with either insulin glargine (n = 331) orNPH insulin (n = 371) met the inclusion criteria. There were no statistically significantdifferences in the occurrence of fetal outcomes studied with the use of insulinglargine compared to NPH insulin.

Conclusions: No evidence has been documented for increased adverse fetaloutcomes with the use of insulin glargine in pregnancy compared to the use of NPHinsulin. These results increase the choices for women requiring basal insulin therapyin pregnancy.

Introduction

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Uncontrolled diabetes in pregnancy is associated with an increased risk of bothmaternal and fetal adverse outcomes. Neonatal complications associated withexposure to hyperglycemia include congenital anomalies, macrosomia, respiratorydistress, and hypoglycemia.[1] However, there is clear evidence that the risks ofmaternal and fetal complications can be reduced by optimizing glucose control

throughout pregnancy.[2,3]

Unfortunately, severe hypoglycemia has been aconsequence of attempting to achieve tight glycemic control in pregnancy. [4] Thepotential for severe hypoglycemia has motivated the development of long-actinginsulin analogues, such as insulin glargine and insulin detemir. Insulin glarginediffers from regular human insulin by the addition of 2 molecules of arginine to the C-terminal of the beta chain and the replacement of aspartic acid with glycine inposition A21, leading to increased stability and duration of action. [5] These molecularmodifications make insulin glargine particularly advantageous in nonpregnantpatients, as the very long elimination half-life (24 hours) results in a lack of a peak ininsulin concentrations.[6] Studies have shown that the use of long-acting insulinanalogues in nonpregnant patients with type 1 diabetes leads to a decreased

incidence of symptomatic, overall, and nocturnal hypoglycemia. In patients with type2 diabetes, improved glycemic control and reduced hypoglycemia have beendemonstrated with long-acting insulin analogues.[7,8]

The prevalence of diabetes in women of childbearing age is increasing, and this willinevitably lead to an increase in the number of pregnancies complicated bydiabetes.[9] These newer long-acting insulin analogues may represent beneficialtreatment options in pregnancy by ensuring that pregnant women achieve glycemiccontrol with a reduced risk of maternal hypoglycemia. However, there are concernsthat the increased affinity for insulin-like growth factor, noted with insulin glargine,may lead to increased fetal growth and other mitogenic effects. [10] Consequently,there is a need to address the issue of fetal safety with the use of insulin glargine inpregnancy. In recent years, a few small case-control/cohort studies and case serieshave reported on the use of insulin glargine in pregnancy. However, small samplesizes limit the ability to draw firm conclusions from the results of these studies. Theobjective of this study was to investigate the fetal safety of insulin glargine comparedwith NPH insulin therapy for the treatment of diabetes in pregnancy through asystematic review and meta-analysis of the literature.

Methods

A systematic literature search was performed using MEDLINE for articles publishedbetween 1980 and June 1, 2010. A similar search was performed in EMBASE,CINAHL, and the Cochrane Central Register for Controlled Trials database from1980 to June 1, 2010. The MeSH and text terms used in the search include thefollowing: glargine, "Hoe 901," Hoe 901, "Hoe-901," Hoe-901, Lantus, optisulin, orinsulin glargine, combined with teratogens, pregnancy complications, prenatalexposure delayed effects, pregnancy, embryo and fetal development, pregnancydisorder, or pregnancy trimesters. In addition, a search of the Web of Science



database was performed from 1980 to June 1, 2010, to retrieve abstracts fromstudies presented at meetings. The authors of identified abstracts were contacted toobtain the full report. Additional studies were identified by hand-searching referencelists from review articles.

SelectionInclusion criteria for the selection of papers consisted of studies that were eithercase –control, cohort, or randomized controlled trials. Studies were included ifwomen in the study were pregnant and had either gestational or pregestationaldiabetes. Studies were excluded if they did not contain human data, did not have acomparison group treated with another form of insulin, did not report fetal outcomesin both groups, did not clearly specify initiation or duration of treatment, or were notwritten in English.

Validity Assessment

The same 2 reviewers (EP and DSF) individually performed an assessment of thequality of the observational studies using the Strengthening of the Reporting ofObservational Studies in Epidemiology Criteria assessment tool. [11] Standardizedforms were used to subsequently extract information from each article that met theinclusion criteria. Outcomes included large size for gestational age, macrosomia,neonatal hypoglycemia, neonatal intensive care unit (NICU) admissions, birthtrauma, congenital anomalies, preterm delivery, perinatal mortality, respiratorydistress syndrome, and hyperbilirubinemia.

Data Abstraction

The same reviewers (EP and DSF) independently reviewed all citations identified bythe systematic search. Disagreements were resolved by consensus.

Quantitative Data Synthesis

Data were combined using a random effects model. Relative risk values fordichotomous data, weighted mean differences (WMDs) for continuous data, and95% confidence intervals were calculated using Review Manager (version 5.0,Copenhagen: Cochrane Collaboration) for each of the aforementioned fetaloutcomes of interest. Heterogeneity was assessed by the χ2 and I2 tests. I2 refers tothe percentage of variability that is due to heterogeneity. While the Q test (χ2)determines the presence or absence of heterogeneity, the I2 test allows for

determination of the extent of heterogeneity. For the purposes of interpretation,I2 values of 25%, 50%, and 75% were considered to indicate low, medium, and highheterogeneity, respectively.[12]

ResultsTrial Flow



Our search resulted in the retrieval and screening of 183 studies (Figure 1). Ofthese, 15 met initial suitability criteria. The majority of studies eliminated were casereports or those that did not report human data. Three of the 15 studies wereabstracts from conference proceedings; their full articles could not be obtained. Fouradditional studies were excluded due to inappropriate study design. Eight studies

met the inclusion criteria and were included in the meta-analysis ().[13 –20]

Table 1. Patient Characteristics for Studies Included in the Meta-Analysis

Reference Study Design

Maternal

Age, y

(mean ±

SD)

Maternal

BMI,

kg/m2(mean

± SD)

PGD

Duration,

y (mean ±

SD)

HbA1c (%)

Total

Mean (±

SD)

Insulin

Dose (3rd

Trimester)

Poyhonen-

Alho(2007)13

Retrospective

cohortanalysis of100 T1Dpregnanciestreated withglargine (n =42) or NPHinsulin (n =49)

N/A N/A Glargine:

14.7 ±1.4;NPH:12.8 ±1.2

1st

trimester:glargine7.6, NPH7.2

Glargine:

82.6 ± 8.4IU; NPH:80.5 ± 4.8IU

3rdtrimester:glargine6.9, NPH6.9

Price(2007)14

Retrospectivecohortanalysis of 32pregnanciestreated withinsulinglargine vs 32NPH-treatedpregnantcontrol pts.;pts. had either

T1D (n = 20)or GD (n = 44)

Glargine:PGD28.4 ±5.8, GD32.0 ±5.5;NPH:PGD34.4 ±4.3, GD34.6 ±

4.8

Glargine:PGD 26.2± 3.7, GD34.0 ± 6.6;NPH: PGD27.0 ± 3.0,GD 33.5 ±7.3

Glargine:T1D 15.1± 6.9;NPH:T1D 13.6± 5.9

3rdtrimester:T1D:glargine6.9, NPH6.7 GD:glargine6.2, NPH6.1

N/A

Di Cianni(2008)15

Retrospectivecohortanalysis of107 T1Dpregnancies

Glargine30.6 ±3.5; NPH30.4 ±4.1

Glargine23.2 ± 4.9;NPH 24.2± 3.4

Glargine16.8 ±8.7; NPH15.9 ±6.5

1sttrimester:glargine7.7, NPH7.6

N/A



treated withglargine (n =43)throughoutpregnancy or

switched toNPH insulin (n= 58)

3rdtrimester:glargine

6.5, NPH6.5

Imbergamo(2008)16

Retrospectivecohortanalysis of 30T1Dpregnanciestreated withglargine (n =

15) or NPHinsulin (n =15)

Glargine27.4 ±5.2; NPH30.1 ±2.4

N/A Glargine14.46 ±6.86;NPH16.13 ±4.35

1sttrimester:glargine6.86,NPH 7.79

Glargine0.89 ±0.21 U/kg;NPH 0.99± 0.19U/kg

3rdtrimester:glargine6.23,NPH 6.47

Egerman(2009)17

Retrospectivecohortanalysis of114 PGD orGDpregnanciestreated with

glargine (n =65) or NPHinsulin (n =49)

Glargine29.7 ±6.5; NPH28.2 ±5.6

Glargine35.9 ± 9.4;NPH 35.0± 8.2

Glargine5 ± 5.5;NPH 4.6± 4.2

1sttrimester:glargine8.0, NPH8.3

Glargine43.1 ±28.8IU/day;NPH 66.4± 34.8IU/day3rd

trimester:glargine7.04,NPH 7.48

Fang

(2009)18

Retrospectivecohortanalysis of112 PGD orGD

pregnanciestreated withglargine (n =52) or NPHinsulin (n =60)

Glargine:PGD30.5 ±5.6, GD31.0 ±5.5;

NPH:PGD30.8 ±4.9, GD30.1 ±5.5

N/A N/A

3rdtrimester:PGD:

glargine6.55,NPH6.70a

N/A

Smith Retrospective Glargine: N/A Glargine: N/A Glargine:



(2009)19 cohortanalysis of 52PGD (T1D [n= 8] or T2D [n= 26]) or GD

pregnanciestreated withglargine (n =27) or NPHinsulin (n =25)

T1D 24.4± 1.5,T2D 31.0± 1.3,GD 35.0

± 1.3;NPH:T1D 22.0± 0, T2D33.3 ±1.1, GD33.0 ±1.8

T1D 12.9± 1.9,T2D 4.5± 1.4;NPH:

T1D 11.0± 0, T2D5.1 ± 1.1

T1D 59 ±13.7IU/day,T2D 65 ±8.2

IU/day,GD 39.7 ±7.7 IU/day

Negrato(2010)20

Prospectivecohort

analysis of138 PGD (n =56) and GD (n= 82)pregnanciestreated withglargine (n =55) or NPHinsulin (n =83); diabeticpregnanciesweremanagedaccording tohospitalprotocol

Glargine:PGD30.4 ±7.1, GD30.9 ±4.2;NPH:PGD28.1 ±7.2, GD31.7 ±6.8

N/A

Glargine6.8 ± 6.3;NPH 7.6± 5.2

3rdtrimester:PGD:glargine7.2, NPH7.6 GD:glargine6.1, NPH

6.1

Glargine:PGD 0.46± 0.24U/kgb, GD0.15 ±0.13U/kgc;NPH:PGD 0.76± 0.34

U/kgb

, GD0.32 ±0.25 U/kgc

BMI = body mass index; GD = gestational diabetes; HbA1c = glycosylatedhemoglobin; N/A = not available; PGD = pregestational diabetes; T1D = type 1diabetes; T2D = type 2 diabetes.

a Data for 18 pts.

b p = 0.003.

c p < 0.01.



Figure 1.

Schematic representation of the review process for article inclusion. WOS = Web of

Science.

Study Characteristics and Data Synthesis

All of the included studies were observational cohort studies. Each study includedpregnant women with either gestational diabetes or pregestational diabetes whowere on insulin glargine and a control group of women on NPH insulin in pregnancy.These 8 studies comprised a total of 702 women with pregestational or gestational



diabetes in pregnancy treated with either insulin glargine (n = 331) or NPH insulin (n= 371).

For each outcome reported, between 2 and 7 studies included sufficient data forextraction. The calculated relative risk ratios for the fetal/neonatal outcomes studied

are presented in . Five studies reported the incidence of large for gestational ageinfants (defined as infant birth weight >90th percentile).[14 –16,18,20] The calculatedrelative risk for large for gestational age infants was not significantly increased (RR1.02; 95% CI 0.80 to 1.31). Three studies reported the incidence of macrosomia(defined as birth weight >4000 g) and demonstrated no significant increased relativerisk (RR 1.28; 95% CI 0.77 to 2.12) (Figure 2).[15,19,20] Several studies reported ratesof neonatal hypoglycemia; however, not all the authors provided a definition fordiagnosis. Four of the 7 studies that looked at this outcome defined neonatalhypoglycemia. Three studies defined neonatal hypoglycemia as capillary bloodglucose <40 mg/dL during the first 24 hours of life. [17,18,20] One study recordedneonatal hypoglycemia if a neonatal blood glucose measurement of <54 mg/dL was

observed on at least 1 occasion. [14] In total, 7 studies reported the rates of neonatalhypoglycemia and none observed an elevated relative risk for this complication (RR0.94; 95% CI 0.64 to 1.39) (Figure 2). [13 –18,20] Six studies reported rates of NICUadmissions and demonstrated no increased relative risk (RR 0.89; 95% CI 0.55 to1.43).[14,15,17 –20] Only 2 studies reported the incidence of shoulder dystocia,demonstrating no significant increased risk (RR 0.22; 95% CI 0.04 to 1.29) in theinsulin glargine group.[13,17] Six studies reported rates of congenital anomalies;however, malformation data from 1 study were excluded, as the control group usingNPH insulin included women who used insulin glargine in the first trimester andswitched to NPH at 8 ± 2.1 weeks gestation.[15] The remaining 5 studies reportingcongenital anomalies were analyzed and showed no increased risk with glargine use(RR 0.97; 95% CI 0.47 to 1.99) (Figure 2).[13,14,16,17,20] Rates of preterm delivery werereported in 2 studies and no increased risk was observed (RR 0.75; 95% CI 0.30 to1.83).[13,18] Four studies reported perinatal mortality rates, showing no increased risk(RR 0.97; 95% CI 0.18 to 5.37).[13,16,19,20] Respiratory distress was reported in 6studies;[13,14,16 –18,20] however, only 1 confirmed respiratory distress syndrome by X-ray.No significant differences in rates of respiratory distress between the insulin glargineand control group were determined (RR 1.53; 95% CI 0.82 to 2.85). Finally, theincidence of hyperbilirubinemia, reported in 6 studies, was not significantly increased(RR 0.95; 95% CI 0.59 to 1.54).[13,15 –18,20]

Table 2. Calculated Relative Risk Ratios for Fetal/Neonatal Outcomes of Interest

Outcome

Insulin Glargine NPH Insulin

Risk Ratio (95%

CI)

Total Pts.

(N)

Events

(n)

Total Pts.

(N)

Events

(n)

Large for gestationalage

197 70 248 881.02 (0.80 to

1.31)



Macrosomia 125 25 166 261.28 (0.77 to

2.12)

Neonatal hypoglycemia 304 57 346 660.94 (0.64 to

1.39)

NICU admissions 274 94 307 93 0.89 (0.55 to1.43)

Shoulder dystocia 107 1 98 70.22 (0.04 to

1.29)

Congenital anomalies 172 14 183 140.97 (0.47 to

1.99)

Preterm 94 9 109 140.75 (0.30 to

1.83)

Perinatal mortality 139 2 172 30.97 (0.18 to

5.37)

Hyperbilirubinemia 272 58 314 600.95 (0.59 to

1.54)

Respiratory distress 261 24 288 151.53 (0.82 to

2.85)

NICU = neonatal intensive care unit.



Figure 2.

Analysis of neonatal outcomes following exposure to insulin glargine therapy versusNPH insulin therapy in pregnancy. M-H = Mantel-Haenszel test.



Five studies reported infant birth weight (in grams) for a combined cohort analysis,including both pregestational and gestational diabetic patients. The resultsdemonstrate no significant difference in WMD between insulin glargine and NPHtreatment groups (WMD 7.74 g; 95% CI –25.44 to 40.92).[13,16,17,19,20] Three studiesreported infant birth weight stratified for type of diabetes (pregestational or

gestational).[14,18,20]

Again, there were no significant differences between the insulinglargine and control group for women with either pregestational (WMD 123.23 g;95% CI –115.94 to 362.39) or gestational diabetes (WMD 101.78 g; 95% CI –56.09to 259.66). Five studies provided data on gestational age at birth (in weeks). [13,15,17 –

19] The weighted mean difference between the groups in the combined cohort did notreveal any significant differences (WMD –0.11 weeks; 95% CI –1.13 to0.91).[13,15,17,19] Similarly, no significant differences were identified between the 2groups when patients were stratified for type of diabetes (pregestational WMD –0.04weeks; 95% CI –2.29 to 2.21; gestational WMD 0.17 weeks; 95% CI –0.29 to0.64).[14,18] Heterogeneity, as determined by the χ2 and I2 tests, was not noted in anyof the analyses, with the exception of the mean difference in gestational age at birth.

Overall, the homogeneity established among the included studies is supportive ofthe ability to combine these studies. Each of the included studies determined thatthere were no significant differences between the insulin glargine and NPHtreatment groups with respect to maternal characteristics such as maternal age,duration of diabetes, gestational age at delivery, prepregnancy weight, and thirdtrimester glycemic control, where data were available. In 1 study, all women startedinsulin glargine prior to conception.[15] Therefore, patients in the NPH grouprepresented women who switched to NPH insulin in the first trimester. However, thepatients were switched to NPH therapy according to the policy adopted in theircenter rather than due to disease severity or inadequate glycemic control. Theauthors reported no differences in glycemic control between the women whoswitched to NPH or continued with insulin glargine. A few of the studies did observedifferences, with respect to maternal characteristics, between the treatment groups.Price et al. observed a difference in mean maternal age between the insulin glargineand NPH groups.[14] Specifically, among patients with type 1 diabetes, the meanmaternal age in the insulin glargine group was significantly lower than the meanmaternal age in the NPH insulin group. Also, among women with gestationaldiabetes, mean weight gain was significantly lower in the insulin glargine groupdespite the fact that the 2 groups received the same dietary advice. However, theauthors suggested that, although possible, it is unlikely that the difference in weight

gain masked an effect of insulin glargine on fetal growth. Imbergamo et al. notedthat the insulin glargine group had significantly lower glycosylated hemoglobin(HbA1c) values at the end of the first trimester and lower fasting and 2-hour post-breakfast blood glucose levels in the first and second trimesters. [16] However, nosignificant differences were determined with respect to any other maternal metabolicparameters. Poyhonen-Alho et al. observed a greater decrease in HbA1c from first tothird trimester in the insulin glargine group when compared to the NPH insulingroup.[13] The authors attribute this difference to the slightly higher, albeit not



significant, first trimester HbA1c values in the insulin glargine group. The most recentstudy, by Negrato et al., also observed notable differences in maternal parametersbetween the treatment groups.[20] In patients with pregestational diabetes, the doseused to treat the insulin glargine group was significantly lower than the dose used inthe NPH group. Significantly higher fasting glycemia levels at 36 weeks' gestation

were also observed in the NPH treatment group compared to the insulin glarginegroup (82.8 ± 14.5 vs 91.6 ± 21.5 mg/dL; p = 0.03).

With respect to neonatal outcomes, 3 studies indicated differences betweentreatment groups.[17,18,20] Fang et al. observed significantly fewer incidences ofmacrosomia (p = 0.04), neonatal hypoglycemia (p = 0.01), and neonatalhyperbilirubinemia (p = 0.05) among pregestational diabetics treated with insulinglargine.[18] Similar differences were not observed among patients with gestationaldiabetes. Egerman et al. noted the incidence of shoulder dystocia was significantlyhigher among the NPH treatment group versus the insulin glargine treatmentgroup.[17] Finally, Negrato et al. observed significantly higher rates of NICU

admission (p = 0.019) and fetal death (p = 0.028) in infants born to women withpregestational diabetes treated with NPH insulin. [20] Among infants born to womenwith gestational diabetes, the occurrence of jaundice (p < 0.01) and congenitalmalformations (p = 0.016) was significantly more frequent in the NPH treatmentgroup versus the insulin glargine treatment group. The authors suggest that thelower dose of insulin used and fewer maternal hypoglycemic events noted in theinsulin glargine treatment group may provide an explanation for the improvedneonatal outcomes observed in the insulin glargine treatment group compared to theNPH treatment group.[20]

DiscussionSeveral new insulin analogues have become available during the past decade, yetdata on the fetal safety of insulin glargine are scarce. By avoiding high peaks ininsulin concentrations, insulin glargine may be beneficial in diabetic pregnancieswhere both tight glycemic control to reduce fetal complications and the prevention ofmaternal hypoglycemia are imperative. In a meta-analysis of 8 studies, we found nostatistically significant increased risk for any of the fetal outcomes studied. Inaddition, there were no statistically significant differences in mean gestational age atbirth or in birth weight between patients treated with either glargine or NPH insulin inwomen with pregestational diabetes, gestational diabetes, or combined cohorts.

We found no statistically significant difference in the incidence of large infants inwomen taking glargine compared with NPH insulin. This is important given glargine'sincreased affinity for the insulin-like growth factor receptor.[10] This has led to aconcern that the use of glargine insulin could, upon crossing the placenta, affectfetal growth and cause an increased rate of macrosomia. Studies have also shownglargine to have an increased ability to stimulate DNA synthesis in humanosteosarcoma cell lines, leading to a concern that glargine could disrupt embryo



fetal development should it cross the placenta. [10] Our meta-analysis also did notshow an increased risk in congenital anomalies with the use of glargine. Similar toother insulin analogues, such as insulin lispro, studies have found that insulinglargine does not cross the placenta at usual doses. [21,22] Recently, experiments weredesigned to examine the extent and rate of transfer of insulin glargine across the

human placenta using the in vitro human placental perfusion model.[22]

Results fromperfusions carried out at therapeutic concentrations of insulin glargine demonstratedno detectable insulin glargine in the fetal circuit. Furthermore, following perfusionswith very high insulin glargine concentrations, the rate of transfer remained low,indicating high capacity of the human placenta to prevent insulin glargine transfer tothe fetal compartment. From these data, one can conclude that, when used attherapeutic concentrations, insulin glargine is not likely to cross the placenta. This isconsistent with our findings that glargine therapy did not lead to an increase in largeinfants or congenital anomalies.

There are several limitations to our study. All of the studies in this meta-analysis

were observational cohort studies. This represents an important limitation, aspatients were not randomized; hence, the studies may be subject to a selection bias,thus limiting the general applicability of the results. In addition, cohort studies maybe especially vulnerable to unknown confounders, representing another potentiallimitation. Therefore, it is possible that the insulin glargine and NPH insulin groupsdiffer in characteristics that were not evaluated and could affect outcome. Forexample, patients using insulin glargine may be of higher socioeconomic status thanthose taking NPH insulin, as insulin glargine is more costly, thus underestimatingany potential harmful effects on the fetus. Furthermore, 7 of the 8 included studieswere retrospective in design. The retrospective study design presents an additionallimitation, as data may be gathered in a less consistent manner. As medical recordsare often used as a source of data, there is the potential for missing information thatmay lead to bias in the study results. Finally, retrospective studies are often limitedwith respect to the number of patients assigned to each treatment group, which maypreclude statistically significant comparisons between groups. Due to the smallsample size of the included studies in this meta-analysis, the clinical impact of theresults may be limited. Future studies should include a prospective randomizedcontrolled trial design to ensure the validity and increase the applicability of theresults determined in this meta-analysis.

In summary, our systematic review and meta-analysis did not detect an increase in

the incidence of adverse fetal outcomes with the use of insulin glargine in pregnancywhen compared with NPH insulin. These results have important clinical implicationsfor the use of insulin glargine in pregnancy and will potentially improve the optionsfor women with diabetes in pregnancy who wish to achieve excellent control of theirglucose levels without the fear of adverse fetal complications.

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Conflict of interest



Authors reported none

Dr. Koren and Dr. Pollex are supported by a grant from the Canadian Institutes of

Health Research (CIHR). Dr. Pollex is a recipient of the Hospital for Sick ChildrenRestracomp Studentship. Dr. Koren is holder of the Research Leadership for BetterPharmacotherapy During Pregnancy and Lactation at the Hospital for Sick Childrenand the Ivey Chair in Molecular Toxicology at the University of Western Ontario.

The Annals of Pharmacotherapy. 2011;45(1):1-8. © 2011 Harvey Whitney BooksCompany

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Safety of Insulin Glargine Use in Pregnancy