5i. Children, pregnancy and breast feeding

5i.1 Background and Evidence Review

Children

There are no data available for the use of SGLT-2 inhibitors in children under 18 years of age, and therefore risks of use posed to this population are unknown.

Pregnancy

There are no human data for the use of SGLT-2 inhibitors during pregnancy. Standard practice has been to switch SGLT-2 inhibitors to insulin in the preconception period and for the duration of pregnancy, hence the lack of safety and efficacy data in this group (81).

In animal studies, at higher than recommended human doses, there have been class-wide toxicity effects highlighting potential links to ossification delays, renal maturation and tubular dilatations (74, 82-84). UK manufacturers are consistent in their advice that, due to a lack of human safety data, SGLT-2 inhibitors should not be used during pregnancy.

Breastfeeding

There are no human data for the use of SGLT-2 inhibitors whilst breastfeeding. Given the highly significant protein binding of SGLT-2 inhibitors, excretion into breast milk is unlikely to be in clinically important quantities (85, 86). Nevertheless, based on data from juvenile toxicity studies in rats whereby renal pelvic and tubular dilatations were observed through exposure via breastmilk, the manufacturers of all UK-licensed SGLT-2 inhibitors are consistent in their advice that extent of excretion in human milk is unknown and therefore a risk to breastfeeding infants/newborns cannot be excluded (74, 82-84).

5i.2 Recommendations for Implementations

1. We suggest that all women of childbearing potential are counselled, prior to conception, on the risks of SGLT-2 inhibitors during pregnancy (Grade 2D).
2. We suggest SGLT-2 inhibitor therapy is discontinued upon planning, suspicion or confirmation of pregnancy (Grade 2D).
3. We suggest SGLT-2 inhibitors are not used in women who are breastfeeding (Grade 2D).

Rationale: There is theoretical evidence to advise against using these drugs in people either planning pregnancy, who become pregnant or who are breastfeeding. Clinical trials in the paediatric setting are suggested.