Postpartum Use of Metformin to Prevent Type 2 Diabetes Mellitus

Metformin is used as first-line therapy but can also be used prophylactically.

Almost three-quarters of women who experience gestational diabetes mellitus (GDM) will eventually develop type 2 diabetes (T2DM) in their lifetime. According to Whelan et al., “GDM is one of the most common complications of pregnancy affecting 6-8% of all pregnancies in the USA or roughly 280,000 patients each year”. Defining plans of care to mitigate this development for patients is crucial for lifelong health. Metformin use and lifestyle modifications have been researched to reduce the likelihood of a patient who had GDM developing T2DM. However, each intervention alone has not shown promising results. The combination of metformin and lifestyle changes, in extensive prospective studies, has been indicated to prove effective in preventing disease progression.

Gestational diabetes mellitus is a known risk factor for T2DM. The American Diabetes Association (ADA) and the American College of Obstetricians and Gynecologists (ACOG) recommend glucose testing for postpartum women who have GDM. Glucose testing is essential for postpartum women because most already meet the criteria for T2DM or pre-diabetes. Also, increased BMI (greater than 25 kg/m²) due to recent pregnancy doubles the risk for T2DM. A prospective assessment of data by Bao et al. from the Nurses’ Health Study (NHS) II for individuals with a prior diagnosis of GDM revealed that for each 1 kg/m² increase in BMI, there was an associated 16% increase in the risk of developing T2DM over the study period. Interestingly, most, if not all, insurance companies do have coverage for a postpartum nutritional consultation. Therefore, postpartum patients have limited access to necessary support and no time to make adjustments for personal recommendations.

The Diabetes Prevention Program (DPP) was a phase 3 trial conducted from 1996 to 2001. It analyzed several interventions for patients with an increased risk of developing T2DM. The DPP included women who had GDM as one of their participant groups. Lifestyle interventions reduced the development of T2DM in that participant group by 53%, and metformin reduced occurrence by 50%. Weight loss, and as a result, reduced BMI, has the strongest correlation with decreased development of T2DM. Several independent studies have analyzed improved metabolic outcomes in patients. They have provided data that support patients have the best outcomes while receiving nutritional counseling by a dietary professional and physical activity counseling with someone like a personal trainer. The more often patients receive both types of counseling, the lower the prevalence of T2DM.

However, these interventions are not achievable for many, especially those who are postpartum patients. Therefore, pharmacologic therapy has emerged as a possible intervention. The DPP included patients who had several risk factors for the development of T2DM, such as increased fasting glucose and failed glucose tolerance tests. In the subgroup of participants who self-reported GDM, “investigators reported a 50.4% reduction in T2DM incidence in those who took metformin versus those who received [the] placebo” (Ratner et al.). After further follow-up with self-reported GDM study participants, the data collected revealed a 40% decreased risk of developing T2DM over a ten-year period. Interestingly, the same drastic benefit was not seen in participants who did not have GDM. The results from these studies led the American Diabetes Association to recommend metformin as a preventative intervention for pre-diabetic patients with a history of GDM. While metformin can be combined with other antihyperglycemic agents, the main benefit of metformin is weight loss, which lowers the risk of developing T2DM.

While the research that has been done has provided positive support for metformin use in postpartum women to reduce the development of T2DM, it is still limited. Lifestyle modifications alone typically have the most impact, but they are not always feasible for postpartum women. According to Whelan et al., Metformin is a safe and feasible addition to lifestyle modifications to assist postpartum patients in improving long-term health.

Practice Pearls:

• Patients who have had gestational diabetes mellitus have an increased risk of developing type 2 diabetes mellitus in the future.
• Lifestyle modifications typically have the most significant impact on positive outcomes for pre-diabetic patients, but they are not always feasible in a postpartum patient.
• Metformin uses in postpartum patients who have had gestational diabetes mellitus has been shown to lower the future development of type 2 diabetes mellitus drastically.

Bao W, Yeung E, Tobias DK, Hu FB, Vaag AA, Chavarro JE, et al. Long-term risk of type 2 diabetes mellitus in relation to BMI and weight change among women with a history of gestational diabetes mellitus: a prospective cohort study. Diabetologia. 2015;58(6):1212–9.

Ratner RE, Christophi CA, Metzger BE, Dabelea D, Bennett PH, Pi-Sunyer X, et al. Prevention of diabetes in women with a history of gestational diabetes: effects of metformin and lifestyle interventions. J Clin Endocrinol Metab. 2008;93(12):4774–9.

Whelan, A.R., Ayala, N.K. & Werner, E.F. Postpartum Use of Weight Loss and Metformin for the Prevention of Type 2 Diabetes Mellitus: a Review of the Evidence. Curr Diab Rep 21, 37 (2021). https://doi.org/10.1007/s11892-021-01410-7

Grace Behr, PharmD/MBA Candidate, Creighton University