Regarding gestational diabetes and Type 2 diabetes: Do you think the recommendation would still be metformin given the newer drugs available? I am also curious if you pay more attention to fasting glucose or A1c? (I am that odd case where my A1c and postprandial numbers are usually fine, but my fasting has always been elevated — both during pregnancy and now 12 years after my last pregnancy).
— Nell PF
It turns out that you are not odd at all. I think understanding the spectrum of blood sugar metabolism is helpful here. More and more, the medical community is recognizing that type 2 diabetes is typically preceded by a series of changes in carbohydrate metabolism and that intervening early can prevent the progression to full-blown diabetes. As an endocrinologist, I am interested in identifying people as early as possible on this path.
Very early on — sometimes in the teens and 20s — insulin resistance appears. Insulin resistance is a process in which the pancreas must produce more insulin to keep blood sugars normal.
Over time, two things can happen. First, the liver becomes less and less responsive to insulin. As a result, it releases too much stored glucose when the body is fasting. This is impaired fasting glucose, and about 10% to 15% of adults in the U.S. have impaired fasting glucose.
The second thing that can happen is that the pancreas cannot continue to churn out more and more insulin in response to high blood sugars after eating. This is impaired glucose tolerance.
Hemoglobin A1c is an average blood sugar over the last three months. So it is entirely possible to have a normal hemoglobin A1c and impaired fasting glucose, particularly if your blood sugars normalize quickly after eating.
The study of metformin preventing Type 2 diabetes after gestational diabetes looked at a group of women with dysglycemia, but the authors defined dysglycemia incredibly broadly. They include women with impaired fasting glucose, impaired glucose tolerance, and prediabetes. Additionally, while they collected BMI, having an elevated BMI was not a requirement for participating in the study. As a result of this study, I advocate for very early treatment for my patients with a history of gestational diabetes.
In the study of semaglutide (Ozempic/Wegovy) preventing progression to Type 2 diabetes, the participants were required to meet the criteria for a diagnosis of prediabetes, and they had to have a BMI of 27 or greater. This means the patients in this study were further along the path to Type 2 diabetes and thus at greater risk of progression.
The way this plays out in my practice is that I consider the inclusion criteria of the clinical trial in my discussion with patients about which option is best for them. If weight loss is one of my patient’s goals, then we might consider semaglutide. If the patient has only very early signs of dysglycemia, we might consider metformin. There are many cases in which I would prescribe both.
Finally, my patients and I have to consider cost. At the time of this writing, semaglutide is not approved for the prevention of progression from prediabetes to Type 2 diabetes. As a result, most insurance companies will not cover it unless the patient meets their criteria for BMI. Metformin has been generic for quite some time and is quite inexpensive and virtually always covered.
Ultimately, the path to Type 2 diabetes is preceded by a number of changes in blood sugar metabolism that can be present for decades. The data supports treating women with a history of gestational diabetes and very early signs of disorder glucose metabolism to prevent the development of Type 2 diabetes.
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