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Improved Prandial Glucose Control With Lower Risk of Hypoglycemia With Nateglinide Than With Glibenclamide in Patients With Maturity-Onset Diabetes of the Young Type 3

¹ Department of Medicine, Helsinki University Hospital, Helsinki, Finland
² Folkhälsan Genetic Institute, Folkhalsan Research Center and Research Program for Molecular Medicine, Helsinki University, Helsinki, Finland
³ Folkhalsan Ostanlid and Malmska Municipal Health Care Center and Hospital, Jakobstad, Finland
⁴ Department of Endocrinology, Wallenberg Laboratory, University Hospital MAS, Lund University, Malmö, Sweden

Address correspondence and reprint requests to Tiinamaija Tuomi, Department of Medicine/Diabetology, Helsinki University Central Hospital, P.O. Box 340, FIN-00029 HUS, Helsinki, Finland. E-mail: tiinamaija.tuomi{at}hus.fi

OBJECTIVE—To study the effect of the short-acting insulin secretagogue nateglinide in patients with maturity-onset diabetes of the young type 3 (MODY3), which is characterized by a defective insulin response to glucose and hypersensitivity to sulfonylureas.

RESEARCH DESIGN AND METHODS—We compared the acute effect of nateglinide, glibenclamide, and placebo on prandial plasma glucose and serum insulin, C-peptide, and glucagon excursions in 15 patients with MODY3. After an overnight fast, they received on three randomized occasions placebo, 1.25 mg glibenclamide, or 30 mg nateglinide before a standard 450-kcal test meal and light bicycle exercise for 30 min starting 140 min after the ingestion of the first test drug.

RESULTS—Insulin peaked earlier after nateglinide than after glibenclamide or placebo (median [interquartile range] time 70 [50] vs. 110 [20] vs. 110 [30] min, P = 0.0002 and P = 0.0025, respectively). Consequently, compared with glibenclamide and placebo, the peak plasma glucose (P = 0.031 and P < 0.0001) and incremental glucose areas under curve during the first 140 min of the test (P = 0.041 and P < 0.0001) remained lower after nateglinide. The improved prandial glucose control with nateglinide was achieved with a lower peak insulin concentration than after glibenclamide (47.0 [26.0] vs. 80.4 [71.7] mU/l; P = 0.023). Exercise did not induce hypoglycemia after nateglinide or placebo, but after glibenclamide six patients experienced symptomatic hypoglycemia and three had to interrupt the test.

CONCLUSIONS—A low dose of nateglinide prevents the acute postprandial rise in glucose more efficiently than glibenclamide and with less stimulation of peak insulin concentrations and less hypoglycemic symptoms.

Abbreviations: FPG, fasting plasma glucose • MODY3, maturity-onset diabetes of the young type 3

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