No reports describing the use of lixisenatide in human pregnancy have been located. The animal data suggest risk, but the presence of maternal toxicity is a confounding factor. However, the absence of human pregnancy experience prevents a better assessment of the embryo-fetal risk. Insulin is the treatment of choice for pregnant diabetic patients because, in general, other hypoglycemic agents do not provide adequate glycemic control. Moreover, insulin does not cross the placenta to the fetus, thus eliminating the additional concern that the drug therapy itself will adversely affect the fetus. Carefully prescribed insulin therapy provides better control of the mother's glucose, thereby preventing the fetal and neonatal complications that occur with this disease. High maternal glucose levels, as may occur in diabetes mellitus, are closely associated with a number of maternal and fetal adverse effects, including fetal structural anomalies if the hyperglycemia occurs early in gestation. To prevent this toxicity, the American College of Obstetricians and Gynecologists recommends that insulin be used for types 1 and 2 diabetes occurring during pregnancy and, if diet therapy alone is not successful, for gestational diabetes (1).
No reports describing the use of lixisenatide during human lactation have been located. The molecular weight (about 4859) suggests that the drug will not be excreted into breast milk. However, small amounts of many high molecular weight compounds are excreted in to milk during the first few days after birth. The effect, if any, of this exposure on a nursing infant is unknown. The most common adverse effects in nonpregnant adults were nausea, vomiting, headache, diarrhea, dizziness, and hypoglycemia (2). If a mother is taking this drug while breastfeeding, her nursing infant should be monitored for these effects.
Lixisenatide (Adlyxin)
Pregnancy Recommendation:No Human Data—Animal Data Suggest Risk
Breastfeeding Recommendation:No Human Data—Probably Compatible
Lixisenatide, given SC, is a glucagon-like peptide-1 receptor agonist that increases glucose-dependent insulin release. It is indicated as an adjunct to diet and exercise to improve glycemic control in type 2 diabetes mellitus. The drug is presumed to be metabolized by proteolytic degradation. The mean terminal half-life was about 3 hours. No information was provided on plasma protein binding (2).
Animal Data: Reproduction studies have been conducted on pregnant rats and rabbits. Rats were given SC doses twice daily during organogenesis, resulting in systemic exposures that were equal to the human clinical dose based on plasma AUC (HCD-AUC). Visceral closure defects (e.g., microphthalmia, bilateral anophthalmia, diaphragmatic hernia) occurred in fetuses as well as stunted growth. However, maternal toxicity (decreased weight, food consumption, and motor activity) also was noted. Skeletal defects and increased pup mortality were observed at doses about 200 times the HCD-AUC. In rabbits given SC doses twice daily during organogenesis that were 6 times the HCD-AUC, multiple visceral and skeletal defects, including closure defects, were noted in fetuses. Maternal toxicity, similar to that observed in rats, was also noted. Interestingly, in a second rabbit study, no drug-related malformations were observed with systemic exposures during organogenesis that were up to 9 times the HCD-AUC. No mention was made concerning maternal toxicity (2).
Carcinogenicity studies have been conducted in mice and rats. In male mice, thyroid C-cell adenomas were observed. Thyroid C-cell adenomas and thyroid C-cell carcinomas were noted in rats. No mutagenic or clastogenic effects were noted in multiple assays No adverse effects were noted in male and female rats (2).
Placental Transfer: It is not known if lixisenatide crosses the human placenta. The molecular weight (about 4859) suggests that it will not cross, at least early in gestation. However, because even high molecular weight compounds cross late in pregnancy, this might also occur with this drug.