Early glycaemic control in metformin users receiving their first add-on therapy: a population-based study of 4,734 people with type 2 diabetes.
OBJECTIVE
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
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.
Department of Clinical Epidemiology, Institute of Clinical Medicine, Aarhus University Hospital, Olof Palmes Allé 43-45, 8200, Aarhus N, Denmark. rwt@clin.au.dk.
Reimar W
RW
Thomsen
Department of Clinical Epidemiology, Institute of Clinical Medicine, Aarhus University Hospital, Olof Palmes Allé 43-45, 8200, Aarhus N, Denmark.
Lisbeth M
LM
Baggesen
Department of Clinical Epidemiology, Institute of Clinical Medicine, Aarhus University Hospital, Olof Palmes Allé 43-45, 8200, Aarhus N, Denmark.
Mette
M
Søgaard
Department of Clinical Epidemiology, Institute of Clinical Medicine, Aarhus University Hospital, Olof Palmes Allé 43-45, 8200, Aarhus N, Denmark.
Lars
L
Pedersen
Department of Clinical Epidemiology, Institute of Clinical Medicine, Aarhus University Hospital, Olof Palmes Allé 43-45, 8200, Aarhus N, Denmark.
Helene
H
Nørrelund
Novo Nordisk Scandinavia AB, Ørestad, Copenhagen, Denmark.
Esben S
ES
Buhl
Novo Nordisk Scandinavia AB, Ørestad, Copenhagen, Denmark.
Christiane L
CL
Haase
Department of Clinical Epidemiology, Institute of Clinical Medicine, Aarhus University Hospital, Olof Palmes Allé 43-45, 8200, Aarhus N, Denmark.
Søren P
SP
Johnsen
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001786:Blood Glucose / Q000032:analysis*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D008297:Male; D008687:Metformin / Q000627:therapeutic use*; D008875:Middle Aged; D013453:Sulfonylurea Compounds / Q000627:therapeutic use*; D016896:Treatment Outcome
D001786:Blood Glucose; D054873:Dipeptidyl-Peptidase IV Inhibitors; D007004:Hypoglycemic Agents; D013453:Sulfonylurea Compounds; D008687:Metformin
Antidiabetic agents; Clinical quality; Comparative effectiveness; Glucose-lowering therapy; Glycaemic control; HbA1c; Hypoglycaemic agents; Metformin; Pharmacoepidemiology; Type 2 diabetes