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Different glucagon effects during DPP-4 inhibition versus SGLT-2 inhibition in metformin-treated type 2 diabetes patients

Alsalim, Wathik LU ; Persson, Margaretha LU and Ahrén, Bo LU (2018) In Diabetes, Obesity and Metabolism
Abstract

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... (More)

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 AUCglucagon, 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 AUCC-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.

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author
organization
publishing date
type
Contribution to journal
publication status
epub
subject
keywords
Dapagliflozin, DPP-4 inhibition, Glucagon, SGLT-2 inhibition, Type 2 diabetes, Vildagliptin
in
Diabetes, Obesity and Metabolism
publisher
Wiley-Blackwell
external identifiers
  • scopus:85044259011
ISSN
1462-8902
DOI
10.1111/dom.13276
language
English
LU publication?
yes
id
6215852c-0df7-4778-888f-e7cf1228298d
date added to LUP
2018-04-09 12:12:46
date last changed
2018-10-28 13:26:40
@article{6215852c-0df7-4778-888f-e7cf1228298d,
  abstract     = {<p>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<sub>glucagon</sub>, 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<sub>C-peptide</sub> (P &lt; .010), higher 4-hour AUC of the intact form of glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) (P &lt; .001) and lower 4-hour AUC of total GIP and GLP-1 (P &lt; .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.</p>},
  author       = {Alsalim, Wathik and Persson, Margaretha and Ahrén, Bo},
  issn         = {1462-8902},
  keyword      = {Dapagliflozin,DPP-4 inhibition,Glucagon,SGLT-2 inhibition,Type 2 diabetes,Vildagliptin},
  language     = {eng},
  month        = {03},
  publisher    = {Wiley-Blackwell},
  series       = {Diabetes, Obesity and Metabolism},
  title        = {Different glucagon effects during DPP-4 inhibition versus SGLT-2 inhibition in metformin-treated type 2 diabetes patients},
  url          = {http://dx.doi.org/10.1111/dom.13276},
  year         = {2018},
}