Empagliflozin for the preservation of beta-cell function in women with recent gestational diabetes: A randomized placebo-controlled trial.

Abstract

Aims: Women with a history of gestational diabetes (GDM) frequently have progressive beta-cell dysfunction, which may result in type 2 diabetes. However, there is a paucity of clinical studies on strategies aiming to preserve beta-cell function in this patient population. This trial evaluated whether empagliflozin can preserve beta-cell function and reduce the prevalence of dysglycemia (prediabetes/diabetes) in women with recent GDM.

Materials and methods: We conducted a double-blind, randomized, placebo-controlled trial where 91 women with recent GDM (6-36 months postpartum) were randomized 1:1 to either empagliflozin 10 mg/day or placebo for 48 weeks. Beta-cell function was assessed by Insulin Secretion-Sensitivity Index-2 (ISSI-2) obtained on an oral glucose tolerance test.

Results: The primary outcome of baseline-adjusted ISSI-2 at 48 weeks was not different between the empagliflozin and placebo group (525 ± 30.4 vs. 560 ± 33.4, p = 0.43). Additional measures of beta-cell function, insulinogenic index/HOMA-IR, and ΔCpep_0-120/Δgluc_0-120 × Matsuda index also did not differ between the groups. While there was no difference in the secondary outcome of prevalence of dysglycemia at 48 weeks between the arms (empagliflozin 65.7% vs. 48.2% in placebo, p = 0.18), the glucose tolerance worsened in 9.4% of participants in the empagliflozin group as compared to 28% in the placebo group (p = 0.08).

Conclusions: Empagliflozin had no significant effect on beta-cell function in women with recent GDM. Given the sample size evaluated in this trial, the use of SGLT-2 inhibitors warrants further study to elucidate their potential impact on T2DM prevention in women with previous GDM.

Trial registration: Clinicaltrials.gov NCT03215069.