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.

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.

• Authors: Satish K Garg, Emily G Moser, Bruce W Bode, Leslie J Klaff, William R Hiatt, Christie Beatson, Janet K Snell-Bergeon
• Journal: Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists (Endocr Pract) 2013 Jan-Feb Vol. 19 Issue 1 Pg. 19-28 ISSN: 1934-2403 [Electronic] United States
• PMID: 23186950 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

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