Sulfonylurea (SU) is first-line treatment of hepatocyte nuclear factor 1-alpha (HNF1A)-diabetes but has limitations due to the risk of hypoglycemia. We hypothesized that SU in combination with the dipeptidyl peptidase-4 inhibitor linagliptin would provide an efficacious treatment with less glycemic variability and hypoglycemia in patients with HNF1A-diabetes compared with SU monotherapy. In a randomized, double-blinded, crossover trial, patients with HNF1A-diabetes (n = 19, [mean ± SD]; age: 43 ± 14 years; BMI 24 ± 3 kg/m2; HbA1c 7.4 ± 0.2% [57 ± 7 mmol/mol]) were randomly assigned to treatment with glimepiride + linagliptin (16 weeks), wash-out (4 weeks) and treatment with glimepiride + placebo (16 weeks) (or vice versa). Treatments were evaluated by continuous glucose monitoring (CGM), HbA1c and a meal test. Compared with glimepiride + placebo, glimepiride + linagliptin showed significant improvements in glycemic variability (assessed as coefficient of variation (CV) and SD on CGM), HbA1c and body weight (Figure 1). Incidence of hypoglycemia (assessed by patient-reported episodes and CGM) was similar between treatments.

In conclusion, linagliptin as add-on treatment to SU in patients with HNF1A-diabetes improved glycemic variability, glycemic control and body weight without increasing the risk of hypoglycemia.


A.S. Christensen: None. S. Haedersdal: None. J. Støy: None. H. Storgaard: None. U. Kampmann: Stock/Shareholder; Spouse/Partner; Novo Nordisk A/S. M. Seghieri: None. J.J. Holst: Advisory Panel; Self; AstraZeneca, Merck Sharp & Dohme Corp., Novo Nordisk A/S, Zealand Pharma A/S. Other Relationship; Spouse/Partner; Antag Therapeutics. T. Hansen: None. F.K. Knop: Advisory Panel; Self; AstraZeneca, Merck Sharp & Dohme Corp., Mundipharma International, Novo Nordisk A/S, Sanofi. Consultant; Self; Carmot Therapeutics, Inc., Eli Lilly and Company, Novo Nordisk A/S. Research Support; Self; AstraZeneca, Gubra, Novo Nordisk A/S, Sanofi, Zealand Pharma A/S. Speaker’s Bureau; Self; AstraZeneca, Lupin Pharmaceuticals, Inc., Merck Sharp & Dohme Corp., Norgine B.V., Novo Nordisk A/S. T. Vilsbøll: Advisory Panel; Self; AstraZeneca, Mundipharma International, Novo Nordisk A/S, Sun Pharmaceutical Industries Ltd. Consultant; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Lilly Diabetes, Medscape, Merck Sharp & Dohme Corp., Sanofi.

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