Clinical trial NCT02607410: Sitagliptin (DPP-4 Inhibitor) and NPH Insulin in Patients With T2D
Official title: Short and Long Term Effects of a Dypeptidil-peptidase-4 Versus Bedtime NPH Insulin as add-on Therapy in Patients With Type 2 Diabetes
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Type 2 Diabetes Mellitus
Keywords: Type 2 diabetes
sitagliptin
NPH insulin
GLP-1
Lead sponsor: University of Sao Paulo General Hospital
Sponsor class: OTHER
Collaborators: name: Fundação de Amparo à Pesquisa do Estado de São Paulo
First posted: 2015-11-18
Enrollment: 40
Sex: ALL
Minimum age (years): 35
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: To compare the short and long term effects of inhibitor of the DPP-IV enzyme, sitagliptin , with bedtime NPH insulin in patients with T2D inadequately controlled with sulphonylurea plus biguanide: effects on beta cell function and on metabolic profile.

Detailed description: Glucose control is fundamental in the treatment of type 2 diabetes (DM2). Studies suggest that drugs that boost levels of glucagon-like peptide (GLP-1) improve glycemic control and have long-term beneficial effect on the function of pancreatic beta cells. Objective: To compare the short and long term effects of sitagliptin (which inhibits the DPP-IV enzyme, increasing the levels of GLP-1) with bedtime NPH insulin in patients with T2D inadequately controlled with sulphonylurea plus biguanide. Effects on beta cell function and on metabolic profile were analyzed. Methods: 40 patients with DM2, HbA1c between 6.6 to 10%, in use of metformin and glibenclamide will be randomized to the addition of sitagliptin (Sitagliptin Group) or of bedtime NPH insulin (NPH Group). Measurements of HbA1c, metabolic and hormonal profile at fasting and post-meal (every 30 minutes for 4 hours) will be evaluated before and after 6 months (short term) and 12 months (long term) of adding sitagliptin or NPH insulin.

Eligibility criteria: Inclusion Criteria

* outpatients with T2D inadequately controlled with metformin plus glyburide
* HbA1c levels between 6.6 and 10%
* body mass index \< 35 kg/m2

Exclusion Criteria

* heart failure
* respiratory failure
* uncontrolled hypertension
* impaired hepatic function
* impaired reanl function
* endocrine disorder
* gastrointestinal disorder
* malignancy
* alcohol abuse
* previous use of insulin
* previou use of based incretin therapy
* type 1 diabetes.

Primary outcomes:
measure: improvement in HbA1c levels
timeFrame: six and twelve months
Secondary outcomes:
measure: improvement of beta cell function with a meal test
timeFrame: six and twelve months after each therapy at times zero, 30, 60, 120 and 180 minutes after meal test
measure: improvement on alpha cell function with a meal test
timeFrame: six and twelve months after each therapy at times zero, 30, 60, 120 and 180 minutes after meal test
Other outcomes:
Locations:
city: Sao Paulo
country: Brazil
facility: University of Sao Paulo General Hospital
Study officials:
affiliation: University of Sao Paulo General Hospital
name: Maria ER Siva, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Muscelli E, Casolaro A, Gastaldelli A, Mari A, Seghieri G, Astiarraga B, Chen Y, Alba M, Holst J, Ferrannini E. Mechanisms for the antihyperglycemic effect of sitagliptin in patients with type 2 diabetes. J Clin Endocrinol Metab. 2012 Aug;97(8):2818-26. doi: 10.1210/jc.2012-1205. Epub 2012 Jun 8.
citation: Aulinger BA, Bedorf A, Kutscherauer G, de Heer J, Holst JJ, Goke B, Schirra J. Defining the role of GLP-1 in the enteroinsulinar axis in type 2 diabetes using DPP-4 inhibition and GLP-1 receptor blockade. Diabetes. 2014 Mar;63(3):1079-92. doi: 10.2337/db13-1455. Epub 2013 Dec 2.
citation: Retnakaran R, Qi Y, Opsteen C, Vivero E, Zinman B. Initial short-term intensive insulin therapy as a strategy for evaluating the preservation of beta-cell function with oral antidiabetic medications: a pilot study with sitagliptin. Diabetes Obes Metab. 2010 Oct;12(10):909-15. doi: 10.1111/j.1463-1326.2010.01254.x.