Background: We conducted a comparison between the dipeptidyl-peptidase-4(DPP-4) inhibitor sitagliptin
versus NPH insulin as an add-on therapies in patients with type 2 diabetes mellitus (T2D) failing oral
medications. The objective was to ascertain the better indication in long-duration diabetes.
Methods: thirty-five T2D patients inadequately controlled with metformin plus glyburide were randomized to
receive sitagliptin (n=18) or bedtime NPH insulin (n=17) for 12 months. HbA1c levels and a metabolic and hormonal
profile at fasting and post-meal (every 30 minutes for 4 hours) were evaluated before and after 6 months
(short-term) and 12 months (long-term) after adding sitagliptin or bedtime NPH insulin to their drug regime.
Results: Sitagliptin and NPH insulin decreased HbA1c levels equally after 6 months (p<0.001) with no further
improvement after 12 months: sitagliptin (8.1±0.7% vs. 7.3±0.8% vs. 7.4±1.9%) and insulin (8.1±0.6% vs.
7.3±0.7% vs. 7.2±1.0%). Fasting glucose, fasting and postprandial triglyceride and C-peptide levels were also
reduced by NPH insulin whereas postprandial insulin was decreased by sitagliptin. Body weight and postchallenge
free fatty acid levels increased with insulin treatment. The transitory suppression (at 6 months) of postprandial
proinsulin levels with both therapies, and of glucagon with sitagliptin, was followed by values similar or
worse to those at pre-treatment.
Conclusion: The use of either NPH insulin or a DPP-4 inhibitor as add-on treatments improves glucose control in
patients with T2D failing on metformin plus glyburide therapy. The results were not attributed to a permanent
improvement in alpha or beta cell function in patients with long-duration diabetes.