Empagliflozin Fails to Preserve Beta-Cell Function After Gestational Diabetes: Trial Finds
Canada: Empagliflozin did not significantly preserve beta-cell function in women with a recent history of gestational diabetes, according to a randomized, placebo-controlled trial published in Diabetes, Obesity and Metabolism. While the study did not show a clear benefit for beta-cell health, researchers observed signals suggesting the drug might help stabilize insulin sensitivity and fasting glucose, highlighting the need for larger, longer studies.
Led by Caroline K. Kramer of the Leadership Sinai Centre for Diabetes at Mount Sinai Hospital, Toronto, the trial addressed an important question: can early pharmacological intervention protect women with prior gestational diabetes mellitus (GDM) from progressing to type 2 diabetes? Women with a history of GDM are known to face a heightened risk of beta-cell decline and subsequent dysglycemia, yet few clinical trials have tested strategies to slow this process.
The double-blind study enrolled 91 participants between 6 and 36 months after childbirth. All had experienced GDM during pregnancy. They were randomly assigned to receive either 10 mg of the sodium–glucose cotransporter-2 (SGLT-2) inhibitor empagliflozin or a placebo once daily for 48 weeks. Investigators used the Insulin Secretion-Sensitivity Index-2 (ISSI-2) derived from an oral glucose tolerance test to evaluate beta-cell function. Additional measures included the insulinogenic index/HOMA-IR and ΔC-peptide/Δglucose multiplied by the Matsuda index.
The study revealed the following findings:
- After nearly a year of treatment, there was no significant difference in beta-cell function between the empagliflozin and placebo groups.
- Baseline-adjusted ISSI-2 scores were 525 for the empagliflozin group and 560 for the placebo group, a nonsignificant difference.
- Other indicators of beta-cell activity and insulin secretion showed similar results, confirming no meaningful preservation of beta-cell capacity with empagliflozin.
- Rates of dysglycemia were comparable, affecting 65.7% of the empagliflozin group and 48.2% of the placebo group.
- Only 9.4% of women on empagliflozin experienced worsening glucose tolerance compared with 28% in the placebo group, a trend approaching statistical significance.
The researchers pointed out that the relatively small sample size limited the trial’s power to detect subtle effects. They also emphasized that although the main beta-cell endpoint was negative, the data hinted at potential benefits in insulin sensitivity and fasting glucose trajectories among those taking empagliflozin.
"Given the persistent risk of type 2 diabetes in women with prior gestational diabetes, the findings underscore the importance of continued investigation. Larger, longer trials are needed to clarify whether SGLT-2 inhibitors like empagliflozin can play a preventive role in this high-risk population," the authors wrote.
"While empagliflozin did not demonstrate a protective effect on beta-cell function over 48 weeks, its favorable influence on glucose trends suggests it may warrant further evaluation as part of a broader strategy to reduce diabetes risk after gestational diabetes," they concluded.
Reference: https://doi.org/10.1111/dom.70146
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