Reimar W Thomsen1, Lisbeth M Baggesen2, Mette Søgaard2, Lars Pedersen2, Helene Nørrelund2, Esben S Buhl3, Christiane L Haase3, Søren P Johnsen2. 1. Department of Clinical Epidemiology, Institute of Clinical Medicine, Aarhus University Hospital, Olof Palmes Allé 43-45, 8200, Aarhus N, Denmark. rwt@clin.au.dk. 2. Department of Clinical Epidemiology, Institute of Clinical Medicine, Aarhus University Hospital, Olof Palmes Allé 43-45, 8200, Aarhus N, Denmark. 3. Novo Nordisk Scandinavia AB, Ørestad, Copenhagen, Denmark.
Abstract
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: 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 diabetespatients 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.
Authors: Marsha A Raebel; Jennifer L Ellis; Emily B Schroeder; Stanley Xu; Patrick J O'Connor; Jodi B Segal; Melissa G Butler; Julie A Schmittdiel; H Lester Kirchner; Glenn K Goodrich; Jean M Lawrence; Gregory A Nichols; Katherine M Newton; Ram D Pathak; John F Steiner Journal: Pharmacoepidemiol Drug Saf Date: 2014-03-18 Impact factor: 2.890
Authors: R W Thomsen; L M Baggesen; E Svensson; L Pedersen; H Nørrelund; E S Buhl; C L Haase; S P Johnsen Journal: Diabetes Obes Metab Date: 2015-06-08 Impact factor: 6.577
Authors: Christianne L Roumie; Robert A Greevy; Carlos G Grijalva; Adriana M Hung; Xulei Liu; Harvey J Murff; Tom A Elasy; Marie R Griffin Journal: JAMA Date: 2014-06-11 Impact factor: 56.272
Authors: Anton Pottegård; Bine Kjøller Bjerregaard; Michael Due Larsen; Kasper Søltoft Larsen; Jesper Hallas; Filip K Knop; Søren Ilsøe Moreno Journal: Eur J Clin Pharmacol Date: 2013-10-22 Impact factor: 2.953
Authors: Helene Hausner; Julie Derving Karsbøl; Anders G Holst; Jacob B Jacobsen; Frank-Dietrich Wagner; Georg Golor; Thomas W Anderson Journal: Clin Pharmacokinet Date: 2017-11 Impact factor: 6.447
Authors: Sanjay Kalra; Silver Bahendeka; Rakesh Sahay; Sujoy Ghosh; Fariduddin Md; Abbas Orabi; Kaushik Ramaiya; Sameer Al Shammari; Dina Shrestha; Khalid Shaikh; Sachitha Abhayaratna; Pradeep K Shrestha; Aravinthan Mahalingam; Mazen Askheta; Aly Ahmed A Rahim; Fatimah Eliana; Hari K Shrestha; Sandeep Chaudhary; Nancy Ngugi; Jean Claude Mbanya; Than Than Aye; Tint Swe Latt; Zhanay A Akanov; Abbas Raza Syed; Nikhil Tandon; A G Unnikrishnan; S V Madhu; Ali Jawa; Subhankar Chowdhury; Sarita Bajaj; Ashok Kumar Das Journal: Indian J Endocrinol Metab Date: 2018 Jan-Feb
Authors: Andrzej Śliwczyński; Melania Brzozowska; Andrzej Jacyna; Petre Iltchev; Tymoteusz Iwańczuk; Waldemar Wierzba; Michał Marczak; Katarzyna Orlewska; Piotr Szymański; Ewa Orlewska Journal: PLoS One Date: 2017-06-05 Impact factor: 3.240
Authors: Kasper Adelborg; Péter Szentkúti; Jan Erik Henriksen; Reimar Wernich Thomsen; Lars Pedersen; Jens Sundbøll; Henrik Toft Sørensen; Ole Hother-Nielsen; Henning Beck-Nielsen Journal: BMJ Open Date: 2020-04-06 Impact factor: 2.692
Authors: Tracey Weiss; Lingfeng Yang; Richard D Carr; Sampriti Pal; Baanie Sawhney; Robert Boggs; Swapnil Rajpathak; Kristy Iglay Journal: BMJ Open Diabetes Res Care Date: 2022-01