CAPÍTULO 3. IMPLEMENTACIÓN DEL SISTEMA PARA EL CONTROL DE LA
3.3 U TILIZACIÓN DE CPTT ACCDR
3.3.2 Catálogos
percentile)
Glibenclamide versus insulin
One RCT reported an RR of 0.22 (95% CI 0.01 to 4.45) for SGA (Figure 26).
None of three cohort studies found a significant difference between the treatment groups [RR 0.78 (95% CI 0.42 to 1.45), no significant
heterogeneity]. Between 0% and 13% of neonates were SGA.
Acarbose versus insulin
No significant difference in rates of SGA neonates was seen in the trial by Bertini (2005)67 when
comparing acarbose with insulin (0% with acarbose and 7% with insulin) – see Figure 27.
Metformin versus insulin
One RCT and two cohort studies examined the effect of metformin versus insulin on rates of SGA neonates (Figure 28). None of the studies found a significant difference between the treatment groups. The RR was 0.74 (95% CI 0.45 to 1.19) for the RCT and 1.39 (95% CI 0.56 to 3.50) for the
TABLE 14 Acceptability of treatment
Study Treatment discontinued because of adverse effects Preference
Glibenclamide
Chmait
200479 Women preferred glibenclamide (none chose insulin) – no information on post-treatment satisfaction
Holt
200852 One woman changed from glibenclamide to insulin because of hypoglycaemia and two for other side
effects (not specified)
In Nasruddin (2009)92 three changed because of
unpredictable hypoglycaemia and four for other unspecified reasons
Women treated with glibenclamide felt that their treatment was both convenient and satisfactory The doctors in the clinic felt that there was less flexibility with glibenclamide because of its long action and therefore it was harder to control the hyperglycaemia
Jacobson
200575 ~ 19 women (8%) stopped glibenclamide (either switching to insulin or continuing without
treatment) for reasons primarily attributed to hypoglycaemia
Kahn
200663 Two women were switched from glibenclamide to insulin because of recurrent hypoglycaemia (BG
< 3.3 mmol/l despite dietary manipulation) Rochon
200683 One woman was switched from glibenclamide to insulin because of symptomatic hypoglycaemia and
one because of patient preference
Metformin
Balani
200889 11 women stopped taking metformin (intolerance in four, refusal to continue in seven)
Coetzee
198670 Two women on metformin stopped treatment because of gastrointestinal side effects; lactic
acidosis was not seen Rowan
200888 Seven women (1.9%) on metformin stopped treatment because of gastrointestinal side effects
32 women (8.8%) on metformin had their dose reduced because of gastrointestinal side effects (but 31 maintained a dose of at least 1000 mg/day) Seven women in the metformin group and three women in the insulin group stopped treatment because of withdrawing consent
No significant difference in maternal serious adverse events (infection, surgery, pelvic arthropathy) No significant difference in neonatal infection requiring hospitalisation
Questionnaire data indicated that women preferred metformin to insulin
Significantly more medication adherence in the insulin than in the metformin group (p < 0.001)
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observational studies (no significant heterogeneity). Between 2% and 19% of neonates were SGA. Neonatal ICU admission
Glibenclamide versus insulin
One RCT found no difference in NICU admission (RR 0.87, 95% CI 0.41 to 1.83).
Of six cohort studies reporting on NICU admission after treatment with glibenclamide or insulin (Figure 29 and below) only one, Jacobson (2005),75
found significantly more NICU admission in the insulin group than in the glibenclamide group (24% vs 15%, p = 0.008); however, NICU length of stay was significantly longer in the glibenclamide group (8.0 ± 10.1 days vs 4.3 ± 9.6 days with insulin, p = 0.002). None of the other studies found a significant difference, and there was no significant difference overall [0.75 (95% CI 0.53 to 1.05)]. The rate of NICU admission was between 6% and 25%. Other studies: Fines (2003),72
Goodman (2008)74 and Langer (2006),76 found no
significant differences.
Acarbose versus insulin
Bertini (2005)67 found no NICU admissions when
comparing acarbose with insulin groups.
Metformin versus insulin
Two RCTs reported no difference in NICU admissions or length of stay (Figure 30).
One cohort study by Balani (2008),89 published as
an abstract, found significantly more admission to the NICU in the insulin group than in the metformin group (19% vs 5%, p = 0.01). The other, Tertti (2008),56 found no significant difference in
treatment days spent at the NICU although the CIs only just overlapped with no difference (RR 0.68, 95% CI 0.45 to 1.02).
Congenital malformations
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Glibenclamide versus insulin
Two RCTs and three cohort studies reported congenital malformations or anomalies after treatment with glibenclamide or insulin (Figure 31). There were no significant differences in congenital malformations or anomalies between the comparison groups (rates of malformations/ anomalies 0% to 10%). In the study by Ramos (2007),61 congenital abnormalities for infants in
the glibenclamide group included patent ductus arteriosus, ventricular septal defect, atrial septal defect, inguinal hernias, intestinal atresia and spine anomaly. No details were reported in the other studies.
Metformin versus insulin
One RCT and three cohort studies reported congenital malformations or anomalies after treatment with metformin or insulin (see Figure 32 and below). There were no significant differences in congenital malformations or anomalies between the comparison groups (rates of malformations/ anomalies 0% to 10%). Other studies: Balani (2008)89 showed no significant difference in rate of
congenital malformations. Respiratory distress
Glibenclamide versus insulin
The Langer (2000)68 RCT reported no difference
between groups, and the Bertini (2005)67 trial
reported that there were no reports of respiratory D
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FIGURE 26 SGA: glibenclamide versus insulin.
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FIGURE 27 SGA: acarbose versus insulin.
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FIGURE 29 NICU admission: glibenclamide versus insulin.
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FIGURE 30 NICU admission: metformin versus insulin.
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48
distress in the glibenclamide group (insulin not reported).
Langer (2000)68 reported lung complications in
8% of infants in the glibenclamide group and 6% of infants in the insulin group (no significant difference).
Four cohort studies reported on respiratory distress (Holt 200852) and oxygen/assisted ventilation
(Jacobson 200575 and Ramos 200761) (Figure
33). None of the studies reported a significant difference between groups (rates 2–9%)
Metformin versus insulin
Two RCTs reported no differences in respiratory distress after treatment with metformin or insulin. One cohort study reported the same (Figure 34). Apgar scores
Glibenclamide versus insulin
Apgar scores at 1 and 5 minutes were reported by one RCT and four cohort studies (see Figure 35 and below). Holt (2008)52 found a significantly higher
1-minute Apgar score in the insulin group than in the glibenclamide group (8.2 vs 7.3, p = 0.05). The RCT by Bertini (2005)67 found a significantly
higher 5-minute Apgar score (9.4 vs 9.0, p = 0.03) in the insulin group than in the glibenclamide group.
The Fines (2003),72 Goodman (2008)74 and
Paterson (2008)77 studies reported no significant
differences in any Apgar scores.
Acarbose versus insulin
Bertini (2005)67 did not find any significant
differences in Apgar scores at 1 or 5 minutes between the acarbose and the insulin groups. Apgar scores at 1 minute were between 8.1 and 8.4, and Apgar scores at 5 minutes were between 9.3 and 9.4 (Figure 36).
Metformin versus insulin
In the RCT by Rowan (2008),88 three neonates in
the metformin group (0.8%) and one (0.3%) in the insulin group had 5-minute Apgar scores below 7; all these infants had Apgar scores of 6.
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FIGURE 32 Congenital malformations/anomalies: metformin versus insulin.
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