Background: Glucagon-like peptide 1 agonists differ in chemical structure, duration of action and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. Methods: We randomly assigned patients with type 2 diabetes and cardiovascular disease to the addition of once-weekly subcutaneous injection of albiglutide (30 mg to 50 mg) or matching placebo to standard care. We hypothesized that albiglutide would be noninferior to placebo for the primary outcome of first occurrence of cardiovascular death, myocardial infarction, or stroke. If noninferiority was confirmed by an upper limit of the 95% confidence interval for the hazard ratio of less than 1.30, closed-testing for superiority was prespecified. Findings: Overall, 9463 participants were followed for a median of 1.6 years. The primary composite outcome occurred in 338 of 4731 patients (7.1%; 4.6 events per 100 person-years) in the albiglutide group and in 428 of 4732 patients (9.0%; 5.9 events per 100 person-years) in the placebo group (hazard ratio, 0.78; 95% confidence interval [CI ], 0.68 to 0.90), indicating that albiglutide, was superior to placebo (P<0.0001 for noninferiority, P=0.0006 for superiority). The incidence of acute pancreatitis (albiglutide 10 patients and placebo 7 patients), pancreatic cancer (6 and 5), medullary thyroid carcinoma (0 and 0), and other serious adverse events did not differ significantly between the two groups. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. (Funded by GlaxoSmithKline; Harmony Outcomes ClinicalTrials.gov number, NCT02465515.) noninferiority; P = 0.06 for superiority). There seems to be variation in the results of existing trials with GLP-1 receptor agonists, which if correct, might reflect drug structure or duration of action, patients studied, duration of follow-up or other factors.
Aim
To evaluate the efficacy and safety of fast‐acting insulin aspart (faster aspart) vs insulin aspart (IAsp) used in continuous subcutaneous insulin infusion (CSII) in participants with type 1 diabetes (T1D).
Materials and Methods
This was a double‐blind, treat‐to‐target, randomized, 16‐week trial investigating CSII treatment with faster aspart (n = 236) or IAsp (n = 236). All available information, regardless of treatment discontinuation, was used for the evaluation of effect.
Results
Faster aspart was non‐inferior to IAsp regarding the change from baseline in glycated haemoglobin (HbA1c; primary endpoint). The mean HbA1c changed from 58.4 mmol/mol (7.5%) at baseline to 57.8 mmol/mol (7.4%) with faster aspart and to 56.8 mmol/mol (7.4%) with IAsp after 16 weeks' treatment, with an estimated treatment difference (ETD) of 1.0 mmol/mol (95% confidence interval [CI] 0.14; 1.87) or 0.09% (95% CI 0.01; 0.17; P < 0.001) for non‐inferiority (0.4% margin; P < 0.02 for statistical significance in favour of IAsp). Faster aspart was superior to IAsp in change from baseline in 1‐hour postprandial glucose (PPG) increment after a meal test (ETD −0.91 mmol/L [95% CI −1.43; −0.39] or −16.4 mg/dL [95% CI −25.7; −7.0]; P = 0.001), with statistically significant reductions also at 30 minutes and 2 hours. The improvement in PPG was reflected in the change from baseline in 1‐hour interstitial glucose increment after all meals (ETD −0.21 mmol/L [95% CI −0.31; −0.11] or −3.77 mg/dL [95% CI −5.53; −2.01]). There was no statistically significant difference in the overall rate of severe or blood glucose‐confirmed hypoglycaemia (estimated rate ratio 1.00 [95% CI 0.85; 1.16]). A numerical imbalance in severe hypoglycaemic episodes between faster aspart and IAsp was seen in the treatment (21 vs 7) and 4‐week run‐in periods (4 vs 0).
Conclusions
Faster aspart provides an effective and safe option for CSII treatment in T1D.
To assess the prevalence and risk factors for early and severe diabetic retinopathy and macular edema in a large cohort of patients with type 2 diabetes Retinopathy grading (any retinopathy, severe retinopathy, diabetic macular edema) and risk factors of 64784 were prospectively recorded between January 2000 and March 2013 and analyzed by Kaplan–Meier analysis and logistic regression. Retinopathy was present in 20.12% of subjects, maculopathy was found in 0.77%. HbA1c > 8%, microalbuminuria, hypertension, BMI > 35 kg/m2 and male sex were significantly associated with any retinopathy, while HbA1c and micro- and macroalbuminuria were the strongest risk predictors for severe retinopathy. Presence of macroalbuminuria increased the risk for DME by 177%. Retinopathy remains a significant clinical problem in patients with type 2 diabetes. Metabolic control and blood pressure are relevant factors amenable to treatment. Concomitant kidney disease identifies high risk patients and should be emphasized in interdisciplinary communication.
Decline of kidney function with time and its influencing factors were investigated in the present longitudinal study in Type 2 (non-insulin-dependent) diabetic patients with clinical diabetic nephropathy. Compared to a control group of Type 2 diabetic patients without proteinuria, the proteinuric patients showed a higher prevalence of hypertension, higher systolic blood pressure values and serum triglyceride levels. The annual loss of glomerular kidney function was much higher in the proteinuric patients (5.3 ml.min-1 x 1.73 m2) than in the control subjects (0.9 ml.min-1 x 1.73 m2). Correlation analyses revealed a close correlation between the annual decrease of kidney function and the factors, systolic and diastolic blood pressure, triglyceride and postprandial blood glucose level as well as body mass index. Regression analyses showed for the first time that in addition to the systolic blood pressure and metabolic control, the triglyceride level is also an independent factor influencing the progression of nephropathy. Higher values of these parameters were associated with a more rapid deterioration of kidney function.
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