TOPLINE:

In patients with HNF1A-related maturity-onset diabetes of the young (HNF1A-MODY), 4 weeks of treatment with the SGLT2 inhibitor empagliflozin, along with other glucose-lowering therapies, improved glycaemic control without a significant increase in hypoglycaemia or other adverse events.

METHODOLOGY:

• Researchers in Denmark conducted a crossover trial to evaluate whether add-on empagliflozin improved glycaemic control in 18 adult patients with HNF1A-MODY (median age, 48 years; 44% men) who were on at least one glucose-lowering medication.
• Patients were randomly assigned to receive either empagliflozin 25 mg once daily (n = 9) or placebo (n = 9) for at least 24 days and then crossed over to the alternate treatment after a washout period of at least 14 days; no patient had used an SGLT2 inhibitor within 60 days before enrolment.
• The primary endpoint was the mean difference in average glucose levels between two groups, measured over 10 days using continuous glucose monitoring (CGM) at the end of each study period.
• Some of the secondary efficacy outcomes included CGM-derived metrics, 24-hour urinary glucose excretion, estimated renal glucose threshold, and fasting plasma glucose levels; one of the safety outcomes was hypoglycaemia on CGM, defined as glucose levels below 3.9 mmol/L for at least 15 minutes.

TAKEAWAY:

• Empagliflozin significantly lowered mean glucose levels by 2.3 mmol/L compared with placebo (P = .0001).
• The time in range (3.9-10.0 mmol/L) was also higher with empagliflozin than with placebo (78% vs 52%; P = .0001), and the time above range (> 10.0 mmol/L) was lower in the empagliflozin vs placebo group (19% vs 47%; P = .0002); the time below range (< 3.9 mmol/L) did not differ significantly.
• Empagliflozin also reduced fasting plasma glucose levels and the estimated renal glucose threshold, while increasing 24-hour urinary glucose excretion.
• Hypoglycaemia rates did not differ between treatments, and no severe hypoglycaemia occurred; adverse events were mostly mild and transient, with no drug-related serious adverse events or discontinuations.

IN PRACTICE:

"Together with published case reports, this study supports that SGLT2 inhibitors have a clinically relevant glucose-lowering effect in individuals with HNF1A-MODY despite the potentially reduced expression of SGLT2 and that empagliflozin could be used as a second-line and/or third-line agent," the authors wrote.

SOURCE:

This study was led by Henrik Maagensen, Copenhagen University Hospital - Steno Diabetes Center Copenhagen, Copenhagen, Denmark. It was published online on January 12, 2026, in Diabetes Care.

LIMITATIONS:

The short study duration and small cohort limited a thorough assessment of safety and long-term benefit. The low number of hypoglycaemia episodes likely left the study underpowered to detect differences between the two groups. The study was not designed as a treat-to-target trial with insulin and sulfonylurea titration, limiting the investigation of hypoglycaemia prevention through medication adjustment.

DISCLOSURES:

This study was indirectly supported by the Novo Nordisk Foundation through unrestricted grants to Steno Diabetes Center Copenhagen. Some authors reported receiving research support, serving on advisory boards, participating in speakers bureaus, owning stocks, or receiving travel reimbursements from multiple pharmaceutical companies, including Novo Nordisk.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.