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

Endocr Pract. Jan-Feb 2013;19(1):19-28. doi: 10.4158/EP12100.OR.

Abstract

Objective: Peripheral 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.

Methods: This 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.

Results: There 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.

Conclusion: Sitagliptin 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.

Trial registration: ClinicalTrials.gov NCT01227460.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Blood Glucose
  • Blood Glucose Self-Monitoring
  • Diabetes Mellitus, Type 1 / blood
  • Diabetes Mellitus, Type 1 / drug therapy*
  • Dipeptidyl-Peptidase IV Inhibitors / pharmacology
  • Dipeptidyl-Peptidase IV Inhibitors / therapeutic use*
  • Double-Blind Method
  • Female
  • Glucagon / blood*
  • Glucagon-Like Peptide 1 / blood*
  • Humans
  • Hypoglycemic Agents / pharmacology
  • Hypoglycemic Agents / therapeutic use
  • Male
  • Middle Aged
  • Postprandial Period / drug effects*
  • Pyrazines / pharmacology
  • Pyrazines / therapeutic use*
  • Sitagliptin Phosphate
  • Treatment Outcome
  • Triazoles / pharmacology
  • Triazoles / therapeutic use*

Substances

  • Blood Glucose
  • Dipeptidyl-Peptidase IV Inhibitors
  • Hypoglycemic Agents
  • Pyrazines
  • Triazoles
  • Glucagon-Like Peptide 1
  • Glucagon
  • Sitagliptin Phosphate

Associated data

  • ClinicalTrials.gov/NCT01227460