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Wathik Alsalim

Research project participant

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


  • Wathik Alsalim
  • Margaretha Persson
  • Bo Ahrén

Summary, in English

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.


  • Diabetes
  • Internal Medicine - Epidemiology
  • EXODIAB: Excellence in Diabetes Research in Sweden
  • EpiHealth: Epidemiology for Health

Publishing year







Diabetes, Obesity and Metabolism





Document type

Journal article




  • Endocrinology and Diabetes


  • Dapagliflozin
  • DPP-4 inhibition
  • Glucagon
  • SGLT-2 inhibition
  • Type 2 diabetes
  • Vildagliptin



Research group

  • Diabetes
  • Internal Medicine - Epidemiology


  • ISSN: 1462-8902