Managing type 2 diabetes or addressing significant weight loss with medications like Semaglutide (marketed as Ozempic) can be life-changing. However, if you are pregnant or planning to become pregnant, it's crucial to understand the safety implications of continuing or starting these medications. Here, we explore what the research says about using Semaglutide during pregnancy, expert recommendations, and practical steps you can take.

What is Semaglutide?

Semaglutide is a GLP-1 receptor agonist that mimics the glucagon-like peptide-1 hormone, enhancing insulin secretion, reducing glucagon release, and slowing gastric emptying. These effects aid in managing blood sugar levels and promoting weight loss. While Semaglutide has shown significant benefits for individuals with type 2 diabetes and obesity, its safety during pregnancy remains a topic of ongoing research and discussion.

Semaglutide works by binding to and activating the GLP-1 receptor, which is involved in glucose regulation and appetite control. This medication can lead to significant reductions in HbA1c levels, an indicator of long-term blood glucose control, and assist in substantial weight reduction in obese patients. The efficacy of Semaglutide has been demonstrated in numerous clinical trials, making it a preferred choice for many healthcare providers. However, its long-term safety profile, particularly during pregnancy, is still under examination.

Current research on Semaglutide and pregnancy

JAMA Internal Medicine (January 2024)

This large study followed approximately 50,000 children whose mothers had type 2 diabetes and used either GLP-1 agonists or insulin during early pregnancy. They checked for birth defects like cleft palate (a condition where the roof of the mouth doesn't form properly) and congenital hydrocephalus (a build-up of fluid in the brain). The study found no increased risk of these defects in children whose mothers took GLP-1 medications compared to those who took insulin. However, the researchers noted that more studies are needed to confirm the results.

Frontiers in Endocrinology (2023)

This comprehensive review looked at 39 different studies to understand how GLP-1 medications and another type of diabetes medication, SGLT2 inhibitors, affect pregnancy and breastfeeding. They found that GLP-1 medications might influence the baby's weight and growth because these drugs can reduce the mother's weight gain and food intake during pregnancy. However, only a few studies included human participants and even those collectively included only 76 children, making it hard to draw firm conclusions.

Potential benefits of Semaglutide:

Semaglutide offers numerous benefits for individuals managing type 2 diabetes and obesity. Its multifaceted effects extend beyond blood sugar control, contributing to overall metabolic health and well-being. Here are some of the key benefits of Semaglutide:

• Blood sugar control: Semaglutide can lower blood glucose levels significantly. By mimicking the GLP-1 hormone, Semaglutide enhances insulin secretion, reduces glucagon release, and slows gastric emptying, leading to improved glycemic control. Clinical trials have shown that Semaglutide can reduce HbA1c levels by up to 1.5-2% in patients with type 2 diabetes, making it an effective option for managing blood sugar levels.
• Significant weight loss: Semaglutide has been shown to promote substantial weight loss, which is particularly beneficial for individuals with obesity or those struggling to manage their weight. In clinical studies, patients taking Semaglutide experienced weight reductions of 10-15% of their body weight over a year. This weight loss is achieved through mechanisms such as appetite suppression, increased satiety, and reduced caloric intake.
• Cardiovascular benefits: Recent studies suggest that Semaglutide may have cardiovascular benefits, particularly in reducing the risk of major adverse cardiovascular events (MACE) such as heart attack, stroke, and cardiovascular death. The SELECT trial and other cardiovascular outcome trials have indicated that Semaglutide can lower the incidence of these events in high-risk populations, offering protective cardiovascular effects beyond glucose control.
• Improved metabolic health: Beyond its primary effects on blood sugar and weight, Semaglutide contributes to overall metabolic health. It helps reduce insulin resistance, lowers blood pressure, and improves lipid profiles by decreasing triglycerides and increasing HDL cholesterol levels. These reduce the risk of metabolic syndrome and its complications.

Potential risks identified in animal studies:

Animal studies have shown that Semaglutide can cause adverse effects such as fetal malformations, pregnancy loss, and growth retardation. These findings are concerning, although they do not always directly translate to humans. The primary risks include:

• Miscarriage: The disruption of normal hormonal balance and reduced maternal nutrient intake can potentially lead to increased rates of miscarriage.
• Lowered birth weights: GLP-1 agonists may indirectly affect fetal growth by influencing maternal weight gain and food consumption, leading to lower birth weights.
  Birth defects: Some animal studies have observed structural abnormalities, though similar outcomes in humans have not been conclusively documented.

Expert recommendations for pregnancy and breastfeeding

Discontinuing GLP-1 medications before pregnancy

If you are planning to become pregnant, discontinue GLP-1 medications at least two months before conception. This helps ensure that the medication is cleared from your system, reducing any potential risk to the developing fetus. You should also consult your provider to discuss alternative options and create a plan for managing your diabetes or weight during pregnancy.

Managing diabetes during pregnancy

The American Diabetes Association (ADA) suggests that insulin is the preferred medication for managing diabetes during pregnancy, including gestational diabetes. Other medications like metformin and glyburide are not first-line treatments during pregnancy because they can cross the placenta and potentially affect the fetus. Insulin does not cross the placenta, making it a safer choice for blood glucose control during pregnancy.

Breastfeeding considerations

Limited research exists on the safety of GLP-1 agonists during breastfeeding. While these medications are unlikely to be absorbed well through an infant's gastrointestinal tract, the current recommendation is to avoid them during breastfeeding due to the lack of definitive safety data. The primary concern is the unknown effects on the infant, as the long-term impact on breastfeeding mothers and their babies has not been thoroughly studied.

The safety of Semaglutide during pregnancy remains uncertain due to the limited research available. Current guidelines recommend discontinuing GLP-1 medications before conception and using alternative treatments like insulin during pregnancy. If you are already taking Semaglutide and discover you are pregnant, work closely with your healthcare provider to manage your diabetes safely and effectively. Maintaining open communication with your healthcare team and adhering to recommended preconception and pregnancy care steps can help ensure the best outcomes for both you and your baby.