Effect of Sitagliptin on Post-Prandial Glucagon and GLP-1 Levels in Patients With Type 1 Diabetes: Investigator-Initiated,Double-Blind,Randomized, Placebo-Controlled Trial |
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| Institution: | 1. Barbara Davis Center for Diabetes, University of Colorado Anschutz Medical Center Aurora, Colorado;2. Diabetes Technology and Therapeutics;3. University of Colorado Anschutz Medical Campus, Aurora, Colorado;4. School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado;5. Atlanta Diabetes Associates, Atlanta, Georgia;6. Rainier Clinical Research Center, Renton, Washington;7. CPC Clinical Research and Department of Medicine/Cardiology, University of Colorado School of Medicine, Aurora, Colorado;1. University of Maryland School of Medicine, Baltimore, Maryland;2. Baltimore Washington Medical Center Baltimore, Maryland;3. University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania;4. Boston University Medical Center, Boston, Massachusetts;1. Sapienza University of Rome Experimental Medicine Department Medical Physiopathology, Food Science and Endocrinology Section Food Science and Human Nutrition Research Unit;1. Department of Endocrinology and Metabolism, National Hospital Organization Kyoto Medical Center, Kyoto, Japan;2. Clinical Research Institute, National Hospital Organization Kyoto Medical Center, Kyoto, Japan;3. Department of Neurology, National Hospital Organization Kyoto Medical Center, Kyoto, Japan;4. Department of Pediatrics, National Hospital Organization Kyoto Medical Center, Kyoto, Japan;5. Department of Endocrinology and Metabolism, Kin-i-kyo Chuo Hospital, Sapporo, Japan |
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| Abstract: | ObjectivePeripheral insulin resistance in type 1 diabetes may be related to a paradoxical postprandial glucagon increase. This study evaluated the effects of sitagliptin (dipeptidyl peptidase-IV DPP-IV] inhibitor, approved for patients with type 2 diabetes), in adults with type 1 diabetes to improve glycemic control through decreasing postprandial glucagon.MethodsThis investigator-initiated, double-blind, randomized-parallel 20-week study enrolled 141 subjects. Subjects received sitagliptin 100 mg/day or placebo for 16 weeks. A subset of 85 patients wore blinded continuous glucose monitors (CGM) for 5 separate 7-day periods. The primary outcome was post-meal (Boost?) reduction in 4-hour glucagon area under the curve (AUC). Secondary endpoints included changes in glycated hemoglobin (A1c), CGM data, insulin dose, glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic peptide (GIP), and C-peptide levels.ResultsThere were no differences at screening between groups; however, after a 4-week run-in phase, A1c was significantly lower in the sitagliptin vs. placebo group. Post-meal GLP-1 levels were higher (P<.001) and GIP levels lower (P = .03), with glucagon suppression at 30 minutes (LS means 23.2 ± 1.9 versus 16.0 ± 1.8; P = .006) in the sitagliptin group at 16 weeks. There were no differences between the groups in change in A1c, insulin dose, weight, or C-peptide after 16 weeks of treatment. However, C-peptide positive patients randomized to sitagliplin had a non-significant trend toward decrease in A1c, mean glucose, and time spent in hyperglycemia.ConclusionSitagliptin use in type 1 diabetes did not change glucagon AUC, A1c, insulin dose, or weight despite post-meal rise in GLP-1 levels. C-peptide positive subjects treated with sitagliptin had a nonsignificant trend in decreasing hyperglycemia, which needs further evaluation. (Endocr Pract. 2013;19:19-28) |
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