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Different glucagon effects during DPP‐4 inhibition versus SGLT‐2 inhibition in metformin‐treated type 2 diabetes patients
Author(s) -
Alsalim Wathik,
Persson Margaretha,
Ahrén Bo
Publication year - 2018
Publication title -
diabetes, obesity and metabolism
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.445
H-Index - 128
eISSN - 1463-1326
pISSN - 1462-8902
DOI - 10.1111/dom.13276
Subject(s) - vildagliptin , dapagliflozin , postprandial , medicine , incretin , endocrinology , glucagon , metformin , type 2 diabetes , glucagon like peptide 1 , area under the curve , diabetes mellitus , insulin
Aims Previous studies have shown that dipeptidyl peptidase (DPP)‐4 inhibition lowers glucagon levels whereas sodium‐glucose co‐transporter 2 (SGLT‐2) inhibition increases them. This study evaluated the extent of these opposite effects in a direct comparative head‐to‐head study. Methods In a single‐centre, randomized study with a cross‐over design, 28 metformin‐treated patients with type 2 diabetes (T2D) (mean age, 63 years; baseline HbA1c, 6.8%) were treated with vildagliptin (50 mg twice daily) or dapagliflozin (10 mg once daily) for 2 weeks, with a 4‐week wash‐out period between the two separate treatments. After each treatment period, a meal test was undertaken, with measurements of islet and incretin hormones and 4‐hour area under the curve (AUC) levels were estimated. Results Fasting glucagon (35.6 ± 2.5 vs 39.4 ± 3.4 pmoL/L; P = .032) and postprandial glucagon (4‐hour AUC glucagon , 32.1 ± 2.3 vs 37.5 ± 2.7 nmoL/L min; P = .001) were ~15% lower after vildagliptin compared to dapagliflozin treatment. This was associated with stronger early (15 minute) C‐peptide response and higher 4‐hour AUC C‐peptide ( P < .010), higher 4‐hour AUC of the intact form of glucose‐dependent insulinotropic polypeptide (GIP) and glucagon‐like peptide‐1 (GLP‐1) ( P < .001) and lower 4‐hour AUC of total GIP and GLP‐1 ( P < .001). Conclusion Treatment with DPP‐4 inhibition with vildagliptin results in 15% lower fasting and postprandial glucagon levels compared to SGLT‐2 inhibition with dapagliflozin. DPP‐4 inhibition also induces more rapid insulin secretion and higher levels of intact incretin hormones, resulting in stronger feedback inhibition of incretin hormone secretion than SGLT‐2 inhibition.