Glucose-Lowering Effects and Low Risk of Hypoglycemia in Patients With Maturity-Onset Diabetes of the Young When Treated With a GLP-1 Receptor Agonist: A Double-Blind, Randomized, Crossover Trial

S. H. Ostoft, J. I. Bagger, Torben Hansen, O. Pedersen, J. Faber, J. J. Holst, F. K. Knop, T. Vilsboll

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OBJECTIVE The most common form of maturity-onset diabetes of the young (MODY), hepatocyte nuclear factor 1 alpha (HNF1A diabetes: MODY3) is often treated with sulfonylureas that confer a high risk of hypoglycemia. We evaluated treatment with GLP-1 receptor agonists (GLP-1RAs) in patients with HNF1A diabetes. RESEARCH DESIGN AND METHODS Sixteen patients with HNF1A diabetes (8 women; mean age 39 years [range 23-67 years]; BMI 24.9 +/- 0.5 kg/m(2) [mean +/- SEM]; fasting plasma glucose [FPG] 9.9 +/- 0.9 mmol/L; HbA(1c) 6.4 +/- 0.2% [47 +/- 3 mmol/mol]) received 6 weeks of treatment with a GLP-1RA (liraglutide) and placebo (tablets), as well as a sulfonylurea (glimepiride) and placebo (injections), in randomized order, in a double-blind, crossover trial. Glimepiride was up-titrated once weekly in a treat-to-target manner; liraglutide was up-titrated once weekly to 1.8 mg once daily. At baseline and at the end of each treatment period a standardized liquid meal test was performed, including a 30-min light bicycle test. RESULTS FPG decreased during the treatment periods (-1.6 +/- 0.5 mmol/L liraglutide [P = 0.012] and 22.8 +/- 0.7 mmol/L glimepiride [P = 0.003]), with no difference between treatments (P = 0.624). Postprandial plasma glucose (PG) responses (total area under the curve) were lower with both glimepiride (2,136 +/- 292 min x mmol/L) and liraglutide (2,624 +/- 340 min x mmol/L) compared with baseline (3,127 +/- 291 min x mmol/L; P <0.001, glimepiride; P = 0.017, liraglutide), with no difference between treatments (P = 0.121). Eighteen episodes of hypoglycemia (PG
TidsskriftDiabetes Care
Udgave nummer7
Sider (fra-til)1797-1805
StatusUdgivet - 2014