BACKGROUND AND OBJECTIVES: To compare cardiovascular disease (CVD) risk associated with 5 different dipeptidyl peptidase-4 inhibitors (DPP-4is) in people with type 2 diabetes. METHODS: We identified 534,327 people who were newly prescribed sitagliptin (n=167,157), vildagliptin (n=67,412), saxagliptin (n=29,479), linagliptin (n=220,672), or gemigliptin (n=49,607) between January 2013 and June 2015 using the claims database of the Korean National Health Insurance System. A Cox proportional hazards model was used to estimate hazard ratios (HRs) for major CVD events (myocardial infarction, stroke, or death) among users of different DPP-4is. The model was adjusted for sex, age, duration of DPP-4i use, use of other glucose-lowering drugs, use of antiplatelet agents, hypertension, dyslipidemia, atrial fibrillation, chronic kidney disease, microvascular complications of diabetes, Charlson comorbidity index, and the calendar index year as potential confounders. RESULTS: Compared to sitagliptin users, the fully adjusted HRs for CVD events were 0.97 (95% confidence interval [CI], 0.94–1.01; p=0.163) for vildagliptin, 0.76 (95% CI, 0.71–0.81; p < 0.001) for saxagliptin, 0.95 (95% CI, 0.92–0.98; p < 0.001) for linagliptin, and 0.84 (95% CI, 0.80–0.88; p < 0.001) for gemigliptin. CONCLUSIONS: Compared to sitagliptin therapy, saxagliptin, linagliptin, and gemigliptin therapies were all associated with a lower risk of cardiovascular events.
Atrial Fibrillation ; Cardiovascular Diseases ; Comorbidity ; Diabetes Mellitus, Type 2 ; Dipeptidyl-Peptidase IV Inhibitors ; Dyslipidemias ; Hypertension ; Infarction ; Korea ; Linagliptin ; National Health Programs ; Platelet Aggregation Inhibitors ; Proportional Hazards Models ; Renal Insufficiency, Chronic ; Sitagliptin Phosphate ; Stroke

BACKGROUND AND OBJECTIVES: To compare cardiovascular disease (CVD) risk associated with 5 different dipeptidyl peptidase-4 inhibitors (DPP-4is) in people with type 2 diabetes. METHODS: We identified 534,327 people who were newly prescribed sitagliptin (n=167,157), vildagliptin (n=67,412), saxagliptin (n=29,479), linagliptin (n=220,672), or gemigliptin (n=49,607) between January 2013 and June 2015 using the claims database of the Korean National Health Insurance System. A Cox proportional hazards model was used to estimate hazard ratios (HRs) for major CVD events (myocardial infarction, stroke, or death) among users of different DPP-4is. The model was adjusted for sex, age, duration of DPP-4i use, use of other glucose-lowering drugs, use of antiplatelet agents, hypertension, dyslipidemia, atrial fibrillation, chronic kidney disease, microvascular complications of diabetes, Charlson comorbidity index, and the calendar index year as potential confounders. RESULTS: Compared to sitagliptin users, the fully adjusted HRs for CVD events were 0.97 (95% confidence interval [CI], 0.94–1.01; p=0.163) for vildagliptin, 0.76 (95% CI, 0.71–0.81; p < 0.001) for saxagliptin, 0.95 (95% CI, 0.92–0.98; p < 0.001) for linagliptin, and 0.84 (95% CI, 0.80–0.88; p < 0.001) for gemigliptin. CONCLUSIONS Compared to sitagliptin therapy, saxagliptin, linagliptin, and gemigliptin therapies were all associated with a lower risk of cardiovascular events.

To investigate conditions that cause temporal lens opacity, we tested chemical and physical factors, such as anaesthesia dose, ocular surface dryness, and infrared (IR) light exposure in anaesthetised C57BL/6 N mice. Mice were anaesthetised with a low (80%; tiletamine/zolazepam 32 mg/kg and xylazine 8 mg/kg, intraperitoneal injection) or high (120%; 48 mg/kg and 12 mg/kg) dose of anaesthetic and examined every 5 min from 10 to 30 min after anaesthesia was induced. Lens opacity levels were assessed and graded (1–6) using the standard classification system. Regardless of the anaesthetic dose, lens opacity grade was 1–2 in moisturised eyes with application of 0.5% carboxymethylcellulose, and 5–6 in dry ocular surface conditions. Lens opacity in mice with high-dose anaesthetic in the dry ocular surface condition was not different from that of mice with low-dose anaesthetic. Lens opacity grade 1–2 was noted in eyes in the wet ocular surface condition, regardless of IR light exposure. During IR light exposure in eyes in the dry ocular surface condition, lens opacity (grade 6) in mice with high-dose anaesthetic was not different from that (grade 6) in mice with low-dose anaesthetic. We demonstrated that ocular surface dryness might be a relevant factor for the formation and progression of lens opacity in anesthetized C57BL/6 N mice. Anaesthesia dose and IR light exposure did not strongly influence lens opacity formation. Furthermore, eyes with corneal dryness-induced lens opacity recovered to normal status without additional intervention.

To investigate conditions that cause temporal lens opacity, we tested chemical and physical factors, such as anaesthesia dose, ocular surface dryness, and infrared (IR) light exposure in anaesthetised C57BL/6 N mice. Mice were anaesthetised with a low (80%; tiletamine/zolazepam 32 mg/kg and xylazine 8 mg/kg, intraperitoneal injection) or high (120%; 48 mg/kg and 12 mg/kg) dose of anaesthetic and examined every 5 min from 10 to 30 min after anaesthesia was induced. Lens opacity levels were assessed and graded (1–6) using the standard classification system. Regardless of the anaesthetic dose, lens opacity grade was 1–2 in moisturised eyes with application of 0.5% carboxymethylcellulose, and 5–6 in dry ocular surface conditions. Lens opacity in mice with high-dose anaesthetic in the dry ocular surface condition was not different from that of mice with low-dose anaesthetic. Lens opacity grade 1–2 was noted in eyes in the wet ocular surface condition, regardless of IR light exposure. During IR light exposure in eyes in the dry ocular surface condition, lens opacity (grade 6) in mice with high-dose anaesthetic was not different from that (grade 6) in mice with low-dose anaesthetic. We demonstrated that ocular surface dryness might be a relevant factor for the formation and progression of lens opacity in anesthetized C57BL/6 N mice. Anaesthesia dose and IR light exposure did not strongly influence lens opacity formation. Furthermore, eyes with corneal dryness-induced lens opacity recovered to normal status without additional intervention.