Risk of overall mortality and cardiovascular events in patients with type 2 diabetes on dual drug therapy including metformin: A large database study from the Cleveland Clinic.

BACKGROUND: The aim of the present study was to assess the risk of overall mortality, coronary artery disease (CAD), and congestive heart failure (CHF) in patients with type 2 diabetes mellitus (T2DM) treated with metformin (MF) and an additional antidiabetic agent. METHODS: A retrospective cohort study was conducted using an academic health center enterprise-wide electronic health record (EHR) system to identify 13,185 adult patients (>18 years) with T2DM from January 2008 to June 2013 and received a prescription for MF in combination with a sulfonylurea (SU; n = 9419), thiazolidinedione (TZD; n = 1846), dipeptidyl peptidase-4 inhibitor (DPP-4i; n = 1487), or a glucagon-like peptide-1 receptor agonist (GLP-1a; n = 433). Multivariate Cox models with propensity analysis were used to compare cohorts, with MF+SU serving as the comparator group. RESULTS: The mean (±SD) age was 60.6 ± 12.6 years, with 54.6% male and 75.8% Caucasians. The median follow-up was 4 years. There were 1077 deaths, 1733 CAD events, and 528 CHF events in 55,100 person-years of follow-up. A higher risk of CHF was observed with MF+DPP-4i use (hazard ratio [HR] 1.104; 95% confidence interval [CI] 1.04-1.17; P = 0.001). A trend towards improved overall survival for users of MF+TZD (HR 0.86; 95% CI 0.74-1.0; P = 0.05) and MF+GLP-1a (HR 0.569; 95% CI 0.30-1.07; P = 0.08) was observed. No significant differences in the risk of CAD were identified. CONCLUSIONS: Consistent with recent studies, our results raise concern for an increased risk of CHF with use of DPP-4i.

Impact of insulin treatment in diabetic macular edema therapy in type 2 diabetes.

OBJECTIVE: To evaluate the impact of insulin therapy on the outcomes of diabetic macular edema (DME) treatment with vascular endothelial growth factor (VEGF) inhibitors in people with type 2 diabetes. METHODS: A retrospective consecutive case series of 95 patients with type 2 diabetes and DME who were treated with anti-VEGF therapy. We examined 2 cohorts: patients taking only oral antidiabetic agents and patients on insulin therapy. The main outcome measures were change in visual acuity and change in central subfield macular thickness measured by spectral-domain optical coherence tomography. The additional variables analyzed included glycated hemoglobin (A1C), creatinine, blood pressure and body mass index and their correlations with clinical findings. RESULTS: Both groups had a statistically significant improvement in visual acuity (oral antidiabetic agents group: 20/61 to 20/49, p=0.003; insulin therapy group: 20/76 to 20/56, p=0.005). There was no difference between groups at initial or 12-month examination (p=0.239 and p=0.489, respectively). From an anatomic standpoint, central subfield macular thickness also improved significantly in both groups: from 454.7 µm to 354.9 µm (p<0.001) in the oral antidiabetic agents group and from 471.5 µm to 368.4 µm (p<0.001) in the insulin therapy group. Again, there was no significant difference between groups at initial or 12-month follow-up examinations (p=0.586 and p=0.591, respectively). Mean A1C levels remained relatively stable during the follow up in both groups. CONCLUSION: Anti-VEGF therapy is a useful treatment for DME. This study suggests that chronic insulin therapy, compared with oral antidiabetic agents, does not modify the anatomic or functional effectiveness of DME treatment.

The impact of metabolic parameters on clinical response to VEGF inhibitors for diabetic macular edema.

AIMS: Evaluate the role of systemic factors on the functional and anatomic outcomes of anti-VEGF therapy for diabetic macular edema (DME). METHODS: A retrospective consecutive case series of 124 patients with DME treated with anti-VEGF therapy was collected. The main outcome measures were change in best corrected visual acuity (BCVA) and change central subfield macular thickness (CST) measured with spectral-domain ocular tomography coherence (SD-OCT); and their correlation with clinical findings. RESULTS: Patients with serum hemoglobin A1c values (HbA1c) ≤ 7.0% had a statistically significant improvement in BCVA (20/66 to 20/43, p < 0.001), and those patients with HBA1c > 7.0% also had a significant but less robust improvement in BCVA (20/78 to 20/62, p = 0.024). CST improved significantly in both groups, but showed a larger magnitude of improvement in the group with better DM control [-140.7 microns (p < 0.001) and -83.3 microns (p < 0.001)]. Mean HBA1c levels remained relatively stable during the follow-up in both groups, but patients with improved glucose control during the study duration had a significantly lower retinal thickness than patients that had a stable or worsening HbA1c (mean final CST of 324.3 versus 390.0 µm, respectively, p = 0.042). Other systemic parameters were not correlated with changes in OCT thickness or BCVA. There was not a significant difference related to number of intravitreal injection in the HbA1c ≤ 7.0% group compared to HbA1c > 7.0% group, mean of 5.48 and 6.0 intravitreal injections respectively (p = 0.362). CONCLUSION: This study suggests that glucose regulation can impact the response to anti-VEGF therapy in the management of DME.