# Comparative Safety of Non-Insulin Agents in Pregnant Women with Pregestational Diabetes

> **NIH NIH R01** · HARVARD UNIVERSITY D/B/A HARVARD SCHOOL OF PUBLIC HEALTH · 2020 · $577,080

## Abstract

In the general population, non-insulin agents have gained wide acceptance for the treatment of type 2 diabetes,
given their efficacy and tolerability when compared to subcutaneous insulin injections. One of the most common
medical complications in pregnancy is pre-gestational diabetes and its management currently focuses on
achieving glucose control with diet, exercise and, if needed, insulin treatment. Both the American Diabetes
Association and the College of Obstetrics and Gynecology recommend to women planning pregnancy and for
those who are pregnant that oral antidiabetic agents be substituted with insulin therapy until further data
regarding safety become available. However, pregnant women are commonly exposed to these agents because
1) guidelines are not universally followed, 2) some women refuse to use insulin, and 3) 50% of pregnancies are
unplanned and if a woman is already using an oral agent there is no time to switch to insulin before
organogenesis. Furthermore, in pregnancy, oral agents have potential benefits with respect to patient
acceptability and adherence, and therefore improved glycemic control and pregnancy outcomes. Even for those
patients for whom oral antidiabetic agents alone are inadequate to achieve glycemic control, they can be used
to reduce insulin dose. Since randomized controlled trials in pregnancy with sufficient sample size to define the
safety of these agents robustly are not realistic, we need timely information based on carefully conducted
observational studies. Until then, the lack of information will continue to be a critical barrier to their use in
pregnancy. Our primary objective is to quantify the risk of maternal and fetal adverse events associated with
specific non-insulin antidiabetic therapies during pregnancy in comparison to insulin alone and metformin alone.
We have established a cohort of 3 million pregnancies linked to infants with longitudinal information on
prescriptions and clinical conditions within two population-based healthcare databases: the Medicaid Analytic
eXtract (MAX) and Truven Health MarketScan (Truven). This study will identify cohorts of over 18,000 (MAX)
and 15,000 (Truven) women with pre-gestational type 2 diabetes who delivered in 2000-2018. Drug exposure
will be determined based on pharmacy dispensing records, and outcomes will be based on in- and outpatient
diagnoses and procedures, using validated definitions. To control for diabetes severity and other confounders,
we will (i) restrict the population to women with type 2 diabetes; (ii) use an active reference group; (iii) use
propensity score stratification to balance aspects of diabetes severity; and (iv) use a novel propensity score
calibration approach to further adjust by incorporating data on glycemic control from subsamples with either
laboratory records or linked electronic medical records. Data from nationally-representative surveys will be used
to ensure generalizability to the US population. Generalized linear mo...

## Key facts

- **NIH application ID:** 9999645
- **Project number:** 5R01HD097778-02
- **Recipient organization:** HARVARD UNIVERSITY D/B/A HARVARD SCHOOL OF PUBLIC HEALTH
- **Principal Investigator:** Sonia Hernandez-Diaz
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $577,080
- **Award type:** 5
- **Project period:** 2019-09-01 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9999645

## Citation

> US National Institutes of Health, RePORTER application 9999645, Comparative Safety of Non-Insulin Agents in Pregnant Women with Pregestational Diabetes (5R01HD097778-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9999645. Licensed CC0.

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