Dapagliflozin and Metformin,Alone and in Combination, in Overweight/Obese Prior GDM Women
Status:
Completed
Trial end date:
2019-03-13
Target enrollment:
Participant gender:
Summary
Women with a history of gestational diabetes (GDM) are at substantially increased risk of
type 2 diabetes mellitus (T2DM). Compared with the general population, these women are more
likely to be overweight or obese. Moreover, weight gain after GDM is significantly associated
with T2DM, independent of baseline body weight. Weight gain, particularly increased central
adiposity after delivery, is strongly associated with deterioration of β-cell compensation
for insulin resistance. Taken together, our findings and other studies support increased
abdominal fat as the strongest factor associated with declining B-cell compensation for
insulin resistance in prior GDM women at high risk for T2DM. Dapagliflozin is a novel highly
selective SGLT2 inhibitor that improves glycemic control by reducing renal glucose
reabsorption leading to urinary glucose excretion. Its efficacy and safety has been studied
in multiple randomized controlled trials including an add-on to metformin compared with a
placebo. To the extent that glucotoxicity contributes to the demise in β-cell function in
subjects with impaired glucose, SGLT2 inhibitors also may prove useful in the treatment of
"prediabetes." An additional secondary benefit of SGLT2 inhibition is the elimination of
calories in the form of glucose. The loss of glucose with attendant caloric loss contributes
to weight loss; in addition, improvements in β cell function have been seen. Weight loss seen
with SGLT2 inhibitors is similar to that seen with glucagon-like peptide 1 analogs, and may
be more acceptable because they are oral agents. A consistent finding in all dapagliflozin
studies has been a reduction in blood pressure. The investigators hypothesize that
combination dapagliflozin -metformin treatment over a 24-week period will have a greater
positive impact on body weight, anthropometric measurements and glycemic and cardiometabolic
parameters than dapagliflozin or metformin monotherapy in overweight/obese at-risk women with
a history of GDM.