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

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.

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.

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.

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.