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
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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. / Ostoft, Signe H; Bagger, Jonatan I; Hansen, Torben; Pedersen, Oluf; Faber, Jens; Holst, Jens Juul; Knop, Filip K; Vilsbøll, Tina.
In: Diabetes Care, Vol. 37, No. 7, 14.06.2014, p. 1797-1805.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - 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
T2 - A Double-Blind, Randomized, Crossover Trial
AU - Ostoft, Signe H
AU - Bagger, Jonatan I
AU - Hansen, Torben
AU - Pedersen, Oluf
AU - Faber, Jens
AU - Holst, Jens Juul
AU - Knop, Filip K
AU - Vilsbøll, Tina
N1 - © 2014 by the American Diabetes Association.
PY - 2014/6/14
Y1 - 2014/6/14
N2 - OBJECTIVE: The most common form of maturity-onset diabetes of the young (MODY), hepatocyte nuclear factor 1α (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; HbA1c 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 -2.8 ± 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 × mmol/L) and liraglutide (2,624 ± 340 min × mmol/L) compared with baseline (3,127 ± 291 min × mmol/L; P < 0.001, glimepiride; P = 0.017, liraglutide), with no difference between treatments (P = 0.121). Eighteen episodes of hypoglycemia (PG ≤3.9 mmol/L) occurred during glimepiride treatment and one during liraglutide treatment.CONCLUSIONS: Six weeks of treatment with glimepiride or liraglutide lowered FPG and postprandial glucose excursions in patients with HNF1A diabetes. The glucose-lowering effect was greater with glimepiride at the expense of a higher risk of exclusively mild hypoglycemia.
AB - OBJECTIVE: The most common form of maturity-onset diabetes of the young (MODY), hepatocyte nuclear factor 1α (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; HbA1c 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 -2.8 ± 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 × mmol/L) and liraglutide (2,624 ± 340 min × mmol/L) compared with baseline (3,127 ± 291 min × mmol/L; P < 0.001, glimepiride; P = 0.017, liraglutide), with no difference between treatments (P = 0.121). Eighteen episodes of hypoglycemia (PG ≤3.9 mmol/L) occurred during glimepiride treatment and one during liraglutide treatment.CONCLUSIONS: Six weeks of treatment with glimepiride or liraglutide lowered FPG and postprandial glucose excursions in patients with HNF1A diabetes. The glucose-lowering effect was greater with glimepiride at the expense of a higher risk of exclusively mild hypoglycemia.
U2 - 10.2337/dc13-3007
DO - 10.2337/dc13-3007
M3 - Journal article
C2 - 24929431
VL - 37
SP - 1797
EP - 1805
JO - Diabetes Care
JF - Diabetes Care
SN - 0149-5992
IS - 7
ER -
ID: 117850945