The effect of alogliptin on pulmonary function in obese patients with type 2 diabetes inadequately controlled by metformin monotherapy.

Background: To observe the effect of alogliptin combined with metformin on pulmonary function in obese patients with type 2 diabetes inadequately controlled by metformin monotherapy (500mg, bid po, for at least 3 months), and evaluate its efficacy and safety. Methods: 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 the control group (n=50) for 26 weeks. The patients in the control group were given metformin (1000mg, bid po) and the patients in the intervention group were given metformin (500mg, bid po) combined with alogliptin (25mg, qd po). All the patients received counseling about diet and exercise from a nutritionist during runin and treatment periods. The primary endpoints were the between-group differences in the changes in pulmonary function parameters (vital capacity [VC]%, forced vital capacity [FVC]%, forced expiratory volume in 1 second (FEV1)%, peak expiratory force [PEF]%, maximal voluntary ventilation [MVV]%, total lung capacity [TLC%], forced expiratory volume in 1second/forced vital capacity [FEV1/FVC%], diffusing capacity for carbon monoxide of lung [DLCO]%, and diffusing capacity for carbon monoxide of lung/unit volume [DLCO/VA%]) between pretherapy and posttreatment. The secondary endpoints were changes from baseline to week 26 in glycosylated hemoglobinA1c (HbA1c), FPG, 2hPG, homeostasis model assessment insulin resistance (HOMA-IR), waist circumference (WC), and BMI. The tertiary endpoints were the changes from baseline to week 26 in blood-fat (total cholesterol [TC], high-density lipoprotein cholesterol [HDL-C], low-density lipoprotein cholesterol [LDL-C], and triglycerides [TG]). The quartus endpoints were the changes from baseline to week 26 in systolic blood pressure (SBP) and diastolic blood pressure (DBP). The 5th endpoints were the changes from baseline to week 26 in oxidative/antioxidative parameters (reactive oxygen species [ROS], malondialdehyde [MDA], superioxide dismutase [SOD], and glutathione peroxidase [GSH-Px]). In addition, safety endpoints were assessed (AEs, clinical laboratory tests, vital signs, and electrocardiographic readings). Results: Eighty-one patients completed our clinical trial: intervention group (n=44) and control group (n=37). At week 26, pulmonary function parameters (VC%, FVC%, FEV1%, PEF%, MVV%, TLC%, FEV1/FVC%, DLCO%, and DLCO/VA%) had increased significantly from pretherapy values in both groups (P<0.05), and the pulmonary function tests were significantly greater (P<0.05) in intervention group than in controls posttherapy. Pulmonary function (FVC%, FEV1%, PEF%, TLC%, FEV1/FVC%, DLCO %, and DLCO/VA%) was lower in the group with HbA1c levels >= 8.0 at 26 weeks, but VC%, FEV1%, MVV%, and TLC% were not significantly lower (P>0.05). Pulmonary function parameters were positively correlated with GSH-Px and SOD and negatively correlated with ROS and MDA. Mean declines in HbA1c, FPG, 2hPG, HOMA-IR, and blood-fat (TC, HDL-C, LDL-C, and TG) were significantly greater (P<0.05) in intervention group compared with the controls, but mean declines in BMI, WC, and BP (SBP, DBP) did not differ significantly between the 2 groups (P>0.05). SOD and GSH-Px increased more (P< 0.05) in the intervention group, compared with the controls; ROS and MDA declined more (P< 0.05) in intervention group, as compared with the control group. The most common AEs were gastrointestinal events, headaches, skin-related AEs (mostly pruritic events), and hypoglycemia. The incidences of AEs did not differ significantly (P>0.05) between the 2 groups except for the headache and skin-related adverse events (the incidence of headache was higher in the intervention group than in controls; P<0.05). No patient died during the study. Conclusion: In patients with type 2 diabetes mellitus (T2DM) inadequately controlled by metformin monotherapy, the addition of alogliptin contributed to clinically significant increases in pulmonary function through regulating glycemia and improving the imbalance of the oxidative-related substances in the serum, without increasing the incidence of hypoglycemia, dyslipidemia, dysarteriotony, and any notable increase in body weight.