Early glycaemic control in metformin users receiving their first add-on therapy: a population-based study of 4,734 people with type 2 diabetes

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 HbA(1c) 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.