The Effect of Alogliptin on Pulmonary Function in Obese Patients With Type 2 Diabetes Inadequately Controlled by Metformin Monotherapy

Objective: To observe the effect of alogliptin combined with metformin on pulmonary function in obese patients with type 2 diabetes inadequately controlled by metformin monotherapy (500 mg, bid po, for at least 3 months), and evaluate its efficacy and safety.

Method: After a 2-week screening period, adult patients (aged 36-72 years) entered a 4-week run-in/stabilization period. Then, patients were randomly assigned to either the intervention group (n=55) or control group (n=50) for 26 weeks. The patients in the control group were given metformin (1,000 mg, bid po) and the patients in the intervention group were given metformin (500 mg, bid po) combined with alogliptin (25 mg, qd po). All the patients received counseling about diet and exercise from a nutritionist during run-in and treatment periods.

The primary endpoints were the between-group differences in the changes pulmonary function parameters [VC%, FVC%, FEV1%, PEF%, MVV%, TLC%, FEV1/FVC%, DLCO%, and DLCO/VA%] between pretherapy and posttreatment. The secondary endpoints were changes from baseline to week 26 in HbA1c, FPG, 2hPG, HOMA-IR, WC, and BMI. The tertiary endpoints were the changes from baseline to week 26 in blood-fat (TC, HDL-C, LDL-C, and TG). The quartus endpoints were the changes from baseline to week 26 in SBP and DBP. The fifth endpoints were the changes from baseline to week 26 in oxidative/antioxidative parameters (ROS, MDA, SOD, and GSH-PX). In addition, safety endpoints were assessed (AEs, clinical laboratory tests, vital signs, and electrocardiographic readings).

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus, Type 2
• Intervention / Treatment: Drug: Alogliptin and Metformin

Detailed Description

Alogliptin was provided by Takeda Chemical industries Ltd in Japan, trade name: Nesina, 25 mg/tablet. Metformin was provided by Bristol Myers Squibb in America, trade name: Glucophage, 500 mg/tablet. Research kits for ROS, MDA, and SOD, GSH-PX were provided by Nanjing Jiancheng Bioengineering Institute in China. Research kits for TC, HDL-C, HDL-C, and TG were provided by were provided by Nanjing Jiancheng Bioengineering Institute in China. The spirometer used for pulmonary function tests was provided by Jaska Corporation in Japan, model number: HI-101

• Study Type: Interventional
• Enrollment (Actual): 81
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 36 years to 72 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 1) Aged from 36 to 72 years of either gender; 2) BMI >28.0 kg/m2, and WC >90 cm (male), or WC >85 cm (female); 3) The patients were diagnosed with T2DM and the serological outcome (7.0%<HbA1c<10.0%) did not reach the therapeutic targets and oral metformin monotherapy (500 mg, bid po, ≥3 months prior to screening); 4) No smoking history, pulmonary disease nor pulmonary infection within a fortnight; 5) Did not have hepatopathy, nephropathy and gastrointestinal disease; and 6) Likely to have good compliance and able to visit our hospital for periodic assessments.

Exclusion Criteria:1) T1DM, gestation and lactation; 2) Renal inadequacy; 3) hypohepatia; 4) Intensive care with insulin treatment; 5) Intolerance to alogliptin and metformin; 6) Heart failure; 7) Had received antidiabetic agents; 8) Antihypertensive drugs can not control the BP adequately or severe uncontrolled hypertension; 9) Cholesterol-lowering drugs can not control the blood-fat adequately; and 10) Use of weight loss drugs.

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Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Alogliptin+metformin; Alogliptin (alogliptin benzoate) is the most recent DPP-4 inhibitor; it entered the market in 2006. It is a potent and highly selective DPP-4 inhibitor with oral antidiabetic activity; Metformin is the most commonly prescribed first-line drug worldwide for the treatment of T2DM, it acts by decreasing both hepatic glucose production and intestinal glucose absorption, while improving insulin sensitivity, metformin as a safe and valid oral antidiabetic drug was recommended to the obese patients with a body mass index (BMI) >30 kg/m2, it has some value in reducing or preventing weight gain and changes in metabolic parameters during treatment, and it can be combinated with other antidiabetic drug	Drug: Alogliptin and Metformin; The patients in the control group were given metformin (1,000 mg, bid po) and the patients in the intervention group were given metformin (500 mg, bid po) combined with alogliptin (25 mg, qd po)
Experimental: metformin; Metformin is the most commonly prescribed first-line drug worldwide for the treatment of T2DM, it acts by decreasing both hepatic glucose production and intestinal glucose absorption, while improving insulin sensitivity, metformin as a safe and valid oral antidiabetic drug was recommended to the obese patients with a body mass index (BMI) >30 kg/m2, it has some value in reducing or preventing weight gain and changes in metabolic parameters during treatment, and it can be combinated with other antidiabetic drug	Drug: Alogliptin and Metformin; The patients in the control group were given metformin (1,000 mg, bid po) and the patients in the intervention group were given metformin (500 mg, bid po) combined with alogliptin (25 mg, qd po)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The primary endpoints were changes from baseline to week 26 in pulmonary function parameters [VC%, FVC%, FEV1%, PEF%, MVV%, TLC%, FEV1/FVC%, DLCO%, and DLCO/VA%] between pretherapy and posttreatment.	26 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
The secondary endpoints were changes from baseline to week 26 in HbA1c in intervention group (n=44) and control group (n=37).	26 weeks
The tertiary endpoints were the changes from baseline to week 26 in blood-fat (TC, HDL-C, LDL-C, and TG) in the intervention group (n=44) and control group (n=37).	26 weeks
The fourth endpoints were the changes from baseline to week 26 in FPG, 2hPG in the intervention group (n=44) and control group (n=37).	26 weeks
The fourth endpoints were the changes from baseline to week 26 in oxidative/antioxidative parameters (ROS, MDA, SOD, and GSH-PX) in the intervention group (n=44) and control group (n=37).	26 weeks
In addition, safety endpoints were assessed (AEs, clinical laboratory tests, vital signs, and electrocardiographic readings)	26 weeks

Other Outcome Measures

Outcome Measure	Time Frame
The changes of BMI from baseline to week 26 in intervention group (n=44) and control group (n=37).	26 weeks

Collaborators and Investigators

• Sponsor: Fourth People's Hospital of Shenyang

Study record dates

Study Major Dates

• Study Start: May 1, 2014
• Primary Completion (Actual): August 1, 2015
• Study Completion (Actual): August 1, 2015

Study Registration Dates

• First Submitted: May 30, 2016
• First Submitted That Met QC Criteria: June 8, 2016
• First Posted (Estimate): June 14, 2016

Study Record Updates

• Last Update Posted (Estimate): June 14, 2016
• Last Update Submitted That Met QC Criteria: June 8, 2016
• Last Verified: June 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Protease Inhibitors; Incretins; Dipeptidyl-Peptidase IV Inhibitors; Metformin; Alogliptin
• Other Study ID Numbers: 20140508