Comparative effectiveness of second line glucose lowering drug treatments using real world data: emulation of a target trial
Objective To build on the recently completed GRADE (Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study) randomised trial examining the comparative effectiveness of second line glucose lowering drugs in achieving and maintaining glycaemic control in adults with type 2 diabet...
Saved in:
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMJ Publishing Group
2023-07-01
|
| Series: | BMJ Medicine |
| Online Access: | https://bmjmedicine.bmj.com/content/2/1/e000419.full |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850138362349879296 |
|---|---|
| author | Jeph Herrin Joseph S Ross Joshua D Wallach Rozalina G McCoy Eric C Polley Yihong Deng |
| author_facet | Jeph Herrin Joseph S Ross Joshua D Wallach Rozalina G McCoy Eric C Polley Yihong Deng |
| author_sort | Jeph Herrin |
| collection | DOAJ |
| description | Objective To build on the recently completed GRADE (Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study) randomised trial examining the comparative effectiveness of second line glucose lowering drugs in achieving and maintaining glycaemic control in adults with type 2 diabetes.Design Emulation of a target trial.Setting Medical and pharmacy claims data from the OptumLabs Data Warehouse, a de-identified US national dataset of beneficiaries of commercially insured and Medicare Advantage plans, 29 March 2013 to 30 June 2021.Participants Adults (≥18 years) with type 2 diabetes who first started taking glimepiride, sitagliptin, liraglutide, insulin glargine, or canagliflozin between 29 March 2013 and 30 June 2021. Participants were treatment naive or were receiving metformin monotherapy at the time of starting the study drug.Main outcome measures The main outcomes were time to primary and secondary metabolic failure of the assigned treatment, calculated as days to haemoglobin A1c levels of ≥7.0% and >7.5%, respectively. Secondary metabolic, cardiovascular, and microvascular outcomes were analysed as specified in the GRADE statistical analysis plan. Propensity scores were estimated with the gradient boosting method, and inverse propensity score weighting was used to emulate randomisation to the treatment groups, which were then compared with Cox proportional hazards regression.(Results The study cohort included participants starting treatment with glimepiride (n=20 511), liraglutide (n=5569), sitagliptin (n=13 039), insulin glargine (n=7262), and canagliflozin (n=5290). The insulin glargine arm was excluded because of insufficient control of confounding. Median times to primary metabolic failure were 439 (95% confidence interval 400 to 489) days in the canagliflozin arm, 439 (426 to 453) days in the glimepiride arm, 624 (567 to 731) days in the liraglutide arm, and 461 (442 to 482) days in the sitagliptin arm. Median time to secondary metabolic failure was also longest in the liraglutide arm. Adults receiving liraglutide had the lowest one year cumulative incidence rate of primary metabolic failure (0.37, 95% confidence interval 0.35 to 0.40) followed by sitagliptin (0.44, 0.43 to 0.45), glimepiride (0.45, 0.44 to 0.45), and canagliflozin (0.46, 0.44 to 0.48). Similarly, the one year cumulative incidence rate of secondary metabolic failure was 0.27 (0.25 to 0.29) in the canagliflozin arm, 0.28 (0.27 to 0.29) in the glimepiride arm, 0.23 (0.21 to 0.26) in the liraglutide arm, and 0.28 (0.27 to 0.29) in the sitagliptin arm. No differences were observed between the study arms in the rates of microvascular and macrovascular complications.Conclusions In this target trial emulation of an expanded GRADE study framework, liraglutide was more effective in achieving and maintaining glycaemic control as a second line glucose lowering drug than canagliflozin, sitagliptin, or glimepiride. |
| format | Article |
| id | doaj-art-ecd168df0594419a8c5745ee205d8d27 |
| institution | OA Journals |
| issn | 2754-0413 |
| language | English |
| publishDate | 2023-07-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | BMJ Medicine |
| spelling | doaj-art-ecd168df0594419a8c5745ee205d8d272025-08-20T02:30:35ZengBMJ Publishing GroupBMJ Medicine2754-04132023-07-012110.1136/bmjmed-2022-000419Comparative effectiveness of second line glucose lowering drug treatments using real world data: emulation of a target trialJeph Herrin0Joseph S Ross1Joshua D Wallach2Rozalina G McCoy3Eric C Polley4Yihong Deng5Section of Cardiovascular Medicine, Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut, USADepartment of Health Policy and Management, Yale School of Public Health, New Haven, CT, USAassistant professorDivision of Community Internal Medicine, Geriatrics, and Palliative Care, Department of Medicine, Mayo Clinic, Rochester, Minnesota, USADepartment of Public Health Sciences, University of Chicago, Chicago, Illinois, USARobert D and Patricia E Kern Center for the Science of Health Care Delivery, Mayo Clinic, Rochester, Minnesota, USAObjective To build on the recently completed GRADE (Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study) randomised trial examining the comparative effectiveness of second line glucose lowering drugs in achieving and maintaining glycaemic control in adults with type 2 diabetes.Design Emulation of a target trial.Setting Medical and pharmacy claims data from the OptumLabs Data Warehouse, a de-identified US national dataset of beneficiaries of commercially insured and Medicare Advantage plans, 29 March 2013 to 30 June 2021.Participants Adults (≥18 years) with type 2 diabetes who first started taking glimepiride, sitagliptin, liraglutide, insulin glargine, or canagliflozin between 29 March 2013 and 30 June 2021. Participants were treatment naive or were receiving metformin monotherapy at the time of starting the study drug.Main outcome measures The main outcomes were time to primary and secondary metabolic failure of the assigned treatment, calculated as days to haemoglobin A1c levels of ≥7.0% and >7.5%, respectively. Secondary metabolic, cardiovascular, and microvascular outcomes were analysed as specified in the GRADE statistical analysis plan. Propensity scores were estimated with the gradient boosting method, and inverse propensity score weighting was used to emulate randomisation to the treatment groups, which were then compared with Cox proportional hazards regression.(Results The study cohort included participants starting treatment with glimepiride (n=20 511), liraglutide (n=5569), sitagliptin (n=13 039), insulin glargine (n=7262), and canagliflozin (n=5290). The insulin glargine arm was excluded because of insufficient control of confounding. Median times to primary metabolic failure were 439 (95% confidence interval 400 to 489) days in the canagliflozin arm, 439 (426 to 453) days in the glimepiride arm, 624 (567 to 731) days in the liraglutide arm, and 461 (442 to 482) days in the sitagliptin arm. Median time to secondary metabolic failure was also longest in the liraglutide arm. Adults receiving liraglutide had the lowest one year cumulative incidence rate of primary metabolic failure (0.37, 95% confidence interval 0.35 to 0.40) followed by sitagliptin (0.44, 0.43 to 0.45), glimepiride (0.45, 0.44 to 0.45), and canagliflozin (0.46, 0.44 to 0.48). Similarly, the one year cumulative incidence rate of secondary metabolic failure was 0.27 (0.25 to 0.29) in the canagliflozin arm, 0.28 (0.27 to 0.29) in the glimepiride arm, 0.23 (0.21 to 0.26) in the liraglutide arm, and 0.28 (0.27 to 0.29) in the sitagliptin arm. No differences were observed between the study arms in the rates of microvascular and macrovascular complications.Conclusions In this target trial emulation of an expanded GRADE study framework, liraglutide was more effective in achieving and maintaining glycaemic control as a second line glucose lowering drug than canagliflozin, sitagliptin, or glimepiride.https://bmjmedicine.bmj.com/content/2/1/e000419.full |
| spellingShingle | Jeph Herrin Joseph S Ross Joshua D Wallach Rozalina G McCoy Eric C Polley Yihong Deng Comparative effectiveness of second line glucose lowering drug treatments using real world data: emulation of a target trial BMJ Medicine |
| title | Comparative effectiveness of second line glucose lowering drug treatments using real world data: emulation of a target trial |
| title_full | Comparative effectiveness of second line glucose lowering drug treatments using real world data: emulation of a target trial |
| title_fullStr | Comparative effectiveness of second line glucose lowering drug treatments using real world data: emulation of a target trial |
| title_full_unstemmed | Comparative effectiveness of second line glucose lowering drug treatments using real world data: emulation of a target trial |
| title_short | Comparative effectiveness of second line glucose lowering drug treatments using real world data: emulation of a target trial |
| title_sort | comparative effectiveness of second line glucose lowering drug treatments using real world data emulation of a target trial |
| url | https://bmjmedicine.bmj.com/content/2/1/e000419.full |
| work_keys_str_mv | AT jephherrin comparativeeffectivenessofsecondlineglucoseloweringdrugtreatmentsusingrealworlddataemulationofatargettrial AT josephsross comparativeeffectivenessofsecondlineglucoseloweringdrugtreatmentsusingrealworlddataemulationofatargettrial AT joshuadwallach comparativeeffectivenessofsecondlineglucoseloweringdrugtreatmentsusingrealworlddataemulationofatargettrial AT rozalinagmccoy comparativeeffectivenessofsecondlineglucoseloweringdrugtreatmentsusingrealworlddataemulationofatargettrial AT ericcpolley comparativeeffectivenessofsecondlineglucoseloweringdrugtreatmentsusingrealworlddataemulationofatargettrial AT yihongdeng comparativeeffectivenessofsecondlineglucoseloweringdrugtreatmentsusingrealworlddataemulationofatargettrial |