GLIMLINA: Glimepiride–linagliptin combination shows potential for HNF1A-MODY
medwireNews: Adding linagliptin to glimepiride treatment reduces some measures of glycemic variability and improves glycemic control in patients with hepatocyte nuclear factor 1-α maturity-onset diabetes of the young (HNF1A-MODY), indicate findings from the GLIMLINA trial.
Speaking at the virtual 56th EASD Annual Meeting, investigator Alexander Christensen (Steno Diabetes Center Copenhagen, Denmark) explained that sulfonylureas are used as first-line treatment in patients with HNF1A-MODY – also known as MODY type 3 – but limitations with these agents include lack of glycemic control when given as monotherapy and a risk for hypoglycemia.
Christensen and colleagues hypothesized that adding the dipeptidyl peptidase-4 inhibitor linagliptin to low-dose treatment with the sulfonylurea glimepiride would result in better glycemic control with lower hypoglycemia risk in this patient population.
The randomized crossover trial included 19 participants who received glimepiride plus linagliptin 5 mg/day or placebo for 16 weeks, followed by a 4-week washout period and crossover to the other treatment for 16 weeks. Glimepiride was given in a treat-to-target manner with a maximum dose of 6 mg/day in both groups; the average dose at the end of treatment was significantly lower when glimepiride was given together with linagliptin than with placebo (2.7 vs 3.4 mg/day).
There was no significant difference in the primary endpoint of mean amplitude of glycemic excursions (MAGE), calculated from 6 days of continuous glucose monitoring (CGM) at the end of treatment, between the linagliptin and placebo treatment periods. Specifically, MAGE decreased by 0.4 mmol/L (7.3 mg/dL) from a baseline of 5.5 mmol/L (99.2 mg/dL) during linagliptin treatment and increased by 0.3 mmol/L (5.5 mg/dL) during the placebo period, resulting in a nonsignificant difference of 0.7 mmol/L (12.7 mg/dL).
However, there was a significant reduction in glycemic variability in the linagliptin versus placebo periods when glycemic variability during CGM was measured by coefficient of variation or standard deviation, with differences of 3.6% and 0.4 mmol/L (7.3 mg/dL), respectively.
Participants also experienced a significantly greater improvement in glycemic control during linagliptin than placebo treatment; mean glycated hemoglobin levels decreased by 0.9% versus 0.4% from a baseline of 7.4% (57 mmol/mol), resulting in a significant difference of 0.5%.
Christensen noted that these benefits occurred without an increase in hypoglycemia risk; there were 15 episodes of hypoglycemia during CGM with linagliptin treatment versus 32 with placebo treatment.
Taken together, these findings suggest that “linagliptin is efficacious as add-on treatment to glimepiride in patients with HNF1A-MODY,” concluded the presenter.
The GLIMLINA results have also been published in Diabetes Care.
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