Search

Aims/hypothesis: The aims of this work were to assess glycaemic control in metformin users receiving their first add-on glucose-lowering therapy and to examine the real-life effectiveness of different add-on drugs., Methods: We carried out a population-based cohort study using healthcare databases in northern Denmark during 2000-2012. We included 4,734 persons who initiated metformin monotherapy and added another glucose-lowering drug within 3 years. Attainment of recommended HbA1c goals within 6 months of add-on was investigated, using Poisson regression analysis adjusted for age, sex, baseline HbA(1c), diabetes duration, complications and Charlson Comorbidity Index., Results: Median metformin treatment duration at intensification was 12 months (interquartile range [IQR] 4-23 months) and pre-intensification HbA(1c) was 8.0% (IQR 7.2-9.2%) (64 [IQR 55-77] mmol/mol). Median HbA(1c) dropped 1.2% (13 mmol/mol) with a sulfonylurea (SU) add-on, 0.8% (9 mmol/mol) with a dipeptidyl peptidase-4 (DPP-4) inhibitor, 1.3% (14 mmol/mol) with a glucagon-like peptide-1 (GLP-1) receptor agonist, 0.9% (10 mmol/mol) with other non-insulin drugs and 2.4% (26 mmol/mol) with insulin. Compared with SU add-on, attainment of HbA(1c) <7% (<53 mmol/mol) was higher with GLP-1 receptor agonists (adjusted RR [aRR] 1.10; 95% CI 1.01, 1.19) and lower with DPP-4 inhibitors (aRR 0.94; 95% CI 0.89, 0.99), other drugs (aRR 0.86; 95% CI 0.77, 0.96) and insulin (aRR 0.88; 95% CI 0.77, 0.99). The proportion of metformin add-on users who attained HbA(1c) <7% (<53 mmol/mol) increased from 46% in 2000-2003 to 59% in 2010-2012, whereas attainment of HbA(1c) <6.5% (<48 mmol/mol) remained 30% among patients aged <65 years without comorbidities., Conclusions/interpretation: Among early type 2 diabetes patients receiving their first metformin add-on treatment, HbA(1c) reduction with different non-insulin drugs is similar to, and comparable with, that observed in randomised trials, yet 41% do not achieve HbA(1c) <7% (<53 mmol/mol) within 6 months.

Aims/hypothesis: Sulfonylureas (SUs) may impair outcome in patients with acute coronary syndrome. Most experimental studies of the myocardial effects of SU treatment are performed in non-diabetic models. We compared the effect of two widely used SUs, glibenclamide (gb) and gliclazide (gc), with high and low myocardial K(ATP) channel affinity, respectively, at therapeutic concentrations on infarct size, left ventricular (LV) function and myocardial glycogen, lactate and alanine content before and after ischaemia/reperfusion (I/R)., Methods: Non-diabetic Wistar and diabetic Goto-Kakizaki rat hearts were investigated in a Langendorff preparation. Gb (0.1 μmol/l) and gc (1.0 μmol/l) were administrated throughout the study. Infarct size was evaluated after 120 min of reperfusion. Myocardial metabolite content was measured before and after ischaemia., Results: Infarct size was smaller in diabetic hearts than in non-diabetic hearts (0.33 ± 0.03 vs 0.51 ± 0.05, p < 0.05). Gb increased infarct size (0.54 ± 0.04 vs 0.33 ± 0.03, p < 0.05) and reduced post-ischaemic LV developed pressure (60 ± 3 vs 76 ± 3 mmHg, p < 0.05) and coronary flow (4.9 ± 0.5 vs 7.1 ± 0.4 ml min(-1) g(-1), p < 0.05) in gb-treated diabetic rats compared with untreated diabetic rats. On comparing gb-treated diabetic rats with untreated diabetic rats, glycogen content was reduced before (9.1 ± 0.6 vs 13.6 ± 1.0 nmol/mg wet weight, p < 0.01) and after ischaemia (0.9 ± 0.2 vs 1.8 ± 0.2 nmol/mg wet weight, p < 0.05), and lactate (4.8 ± 0.4 vs 3.2 ± 0.3 nmol/mg wet weight, p < 0.01) and alanine (1.38 ± 0.12 vs 0.96 ± 0.09 nmol/mg wet weight, p < 0.05) contents were increased during reperfusion. Gc-treatment of diabetic and non-diabetic rats did not affect any of the measured variables., Conclusions/interpretations: Gb, but not gc, exacerbates I/R injury and deteriorates LV function in diabetic hearts. These effects of gb on diabetic hearts may be due to detrimental effects on myocardial carbohydrate metabolism.