Stratified glucose-lowering response to vildagliptin and pioglitazone by obesity and hypertriglyceridemia in a randomized crossover trial
BackgroundUnderstanding which group of patients with type 2 diabetes will have the most glucose lowering response to certain medications (which target different aspects of glucose metabolism) is the first step in precision medicine.AimsWe hypothesized that people with type 2 diabetes who generally h...
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Frontiers Media S.A.
2023-01-01
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| Series: | Frontiers in Endocrinology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fendo.2022.1091421/full |
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| author | Rebecca Brandon Rebecca Brandon Yannan Jiang Yannan Jiang Rui Qian Yeu Rui Qian Yeu Ry Tweedie-Cullen Ry Tweedie-Cullen Kate Smallman Glenn Doherty Kerry A. Macaskill-Smith Rebekah J. Doran Penny Clark Allan Moffitt Troy Merry Troy Merry Norma Nehren Frances King Jennie Harré Hindmarsh Megan Patricia Leask Megan Patricia Leask Megan Patricia Leask Tony R. Merriman Tony R. Merriman Tony R. Merriman Brandon Orr-Walker Peter R. Shepherd Peter R. Shepherd Ryan Paul Ryan Paul Rinki Murphy Rinki Murphy |
| author_facet | Rebecca Brandon Rebecca Brandon Yannan Jiang Yannan Jiang Rui Qian Yeu Rui Qian Yeu Ry Tweedie-Cullen Ry Tweedie-Cullen Kate Smallman Glenn Doherty Kerry A. Macaskill-Smith Rebekah J. Doran Penny Clark Allan Moffitt Troy Merry Troy Merry Norma Nehren Frances King Jennie Harré Hindmarsh Megan Patricia Leask Megan Patricia Leask Megan Patricia Leask Tony R. Merriman Tony R. Merriman Tony R. Merriman Brandon Orr-Walker Peter R. Shepherd Peter R. Shepherd Ryan Paul Ryan Paul Rinki Murphy Rinki Murphy |
| author_sort | Rebecca Brandon |
| collection | DOAJ |
| description | BackgroundUnderstanding which group of patients with type 2 diabetes will have the most glucose lowering response to certain medications (which target different aspects of glucose metabolism) is the first step in precision medicine.AimsWe hypothesized that people with type 2 diabetes who generally have high insulin resistance, such as people of Māori/Pacific ethnicity, and those with obesity and/or hypertriglyceridemia (OHTG), would have greater glucose-lowering by pioglitazone (an insulin sensitizer) versus vildagliptin (an insulin secretagogue).MethodsA randomised, open-label, two-period crossover trial was conducted in New Zealand. Adults with type 2 diabetes, HbA1c>58mmol/mol (>7.5%), received 16 weeks of either pioglitazone (30mg) or vildagliptin (50mg) daily, then switched to the other medication over for another 16 weeks of treatment. Differences in HbA1c were tested for interaction with ethnicity or OHTG, controlling for baseline HbA1c using linear mixed models. Secondary outcomes included weight, blood pressure, side-effects and diabetes treatment satisfaction.Results346 participants were randomised (55% Māori/Pacific) between February 2019 to March 2020. HbA1c after pioglitazone was lower than after vildagliptin (mean difference -4.9mmol/mol [0.5%]; 95% CI -6.3, -3.5; p<0.0001). Primary intention-to-treat analysis showed no significant interaction effect by Māori/Pacific vs other ethnicity (1.5mmol/mol [0.1%], 95% CI -0.8, 3.7), and per-protocol analysis (-1.2mmol/mol [0.1%], 95% CI -4.1, 1.7). An interaction effect (-4.7mmol/mol [0.5%], 95% CI -8.1, -1.4) was found by OHTG status. Both treatments generated similar treatment satisfaction scores, although there was greater weight gain and greater improvement in lipids and liver enzymes after pioglitazone than vildagliptin.ConclusionsComparative glucose-lowering by pioglitazone and vildagliptin is not different between Māori/Pacific people compared with other New Zealand ethnic groups. Presence of OHTG predicts greater glucose lowering by pioglitazone than vildagliptin.Clinical trial registrationwww.anzctr.org.au, identifier (ACTRN12618001907235). |
| first_indexed | 2024-04-10T23:52:52Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 1664-2392 |
| language | English |
| last_indexed | 2024-04-10T23:52:52Z |
| publishDate | 2023-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Endocrinology |
| spelling | doaj.art-cffdbcc133504c5d9b4a6129c12786b92023-01-10T15:07:17ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922023-01-011310.3389/fendo.2022.10914211091421Stratified glucose-lowering response to vildagliptin and pioglitazone by obesity and hypertriglyceridemia in a randomized crossover trialRebecca Brandon0Rebecca Brandon1Yannan Jiang2Yannan Jiang3Rui Qian Yeu4Rui Qian Yeu5Ry Tweedie-Cullen6Ry Tweedie-Cullen7Kate Smallman8Glenn Doherty9Kerry A. Macaskill-Smith10Rebekah J. Doran11Penny Clark12Allan Moffitt13Troy Merry14Troy Merry15Norma Nehren16Frances King17Jennie Harré Hindmarsh18Megan Patricia Leask19Megan Patricia Leask20Megan Patricia Leask21Tony R. Merriman22Tony R. Merriman23Tony R. Merriman24Brandon Orr-Walker25Peter R. Shepherd26Peter R. Shepherd27Ryan Paul28Ryan Paul29Rinki Murphy30Rinki Murphy31Department of Medicine, Faculty of Medical and Health Sciences, The University of Auckland, Auckland, New ZealandMaurice Wilkins Centre for Molecular Biodiscovery, Auckland, New ZealandDepartment of Statistics, Faculty of Sciences, The University of Auckland, Auckland, New ZealandNational Institute for Health Innovation, School of Population Health, The University of Auckland, Auckland, New ZealandDepartment of Medicine, Faculty of Medical and Health Sciences, The University of Auckland, Auckland, New ZealandMaurice Wilkins Centre for Molecular Biodiscovery, Auckland, New ZealandDepartment of Medicine, Faculty of Medical and Health Sciences, The University of Auckland, Auckland, New ZealandMaurice Wilkins Centre for Molecular Biodiscovery, Auckland, New ZealandDiabetes Foundation Aotearoa, Auckland, New ZealandTongan Health Society, Auckland, New ZealandVentures/Pinnacle Incorporated, Hamilton, New ZealandVentures/Pinnacle Incorporated, Hamilton, New ZealandVentures/Pinnacle Incorporated, Hamilton, New ZealandProcare Primary Health Organisation, Auckland, New ZealandMaurice Wilkins Centre for Molecular Biodiscovery, Auckland, New ZealandDiscipline of Nutrition, University of Auckland, Auckland, New Zealand0Te Hiku Hauora, Northland District Health Board, Kaitaia, New Zealand1Ngāti Porou Hauora, Tairāwhiti, New Zealand1Ngāti Porou Hauora, Tairāwhiti, New ZealandMaurice Wilkins Centre for Molecular Biodiscovery, Auckland, New Zealand2Department of Biochemistry, University of Otago, Dunedin, New Zealand3Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, Birmingham, AL, United StatesMaurice Wilkins Centre for Molecular Biodiscovery, Auckland, New Zealand2Department of Biochemistry, University of Otago, Dunedin, New Zealand3Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, Birmingham, AL, United States4Middlemore Clinical Trials, Auckland, New ZealandMaurice Wilkins Centre for Molecular Biodiscovery, Auckland, New Zealand5Department of Molecular Medicine and Pathology, School of Medical Sciences, The University of Auckland, Auckland, New ZealandMaurice Wilkins Centre for Molecular Biodiscovery, Auckland, New Zealand6Department of Medicine, University of Waikato, Waikato, New ZealandDepartment of Medicine, Faculty of Medical and Health Sciences, The University of Auckland, Auckland, New ZealandMaurice Wilkins Centre for Molecular Biodiscovery, Auckland, New ZealandBackgroundUnderstanding which group of patients with type 2 diabetes will have the most glucose lowering response to certain medications (which target different aspects of glucose metabolism) is the first step in precision medicine.AimsWe hypothesized that people with type 2 diabetes who generally have high insulin resistance, such as people of Māori/Pacific ethnicity, and those with obesity and/or hypertriglyceridemia (OHTG), would have greater glucose-lowering by pioglitazone (an insulin sensitizer) versus vildagliptin (an insulin secretagogue).MethodsA randomised, open-label, two-period crossover trial was conducted in New Zealand. Adults with type 2 diabetes, HbA1c>58mmol/mol (>7.5%), received 16 weeks of either pioglitazone (30mg) or vildagliptin (50mg) daily, then switched to the other medication over for another 16 weeks of treatment. Differences in HbA1c were tested for interaction with ethnicity or OHTG, controlling for baseline HbA1c using linear mixed models. Secondary outcomes included weight, blood pressure, side-effects and diabetes treatment satisfaction.Results346 participants were randomised (55% Māori/Pacific) between February 2019 to March 2020. HbA1c after pioglitazone was lower than after vildagliptin (mean difference -4.9mmol/mol [0.5%]; 95% CI -6.3, -3.5; p<0.0001). Primary intention-to-treat analysis showed no significant interaction effect by Māori/Pacific vs other ethnicity (1.5mmol/mol [0.1%], 95% CI -0.8, 3.7), and per-protocol analysis (-1.2mmol/mol [0.1%], 95% CI -4.1, 1.7). An interaction effect (-4.7mmol/mol [0.5%], 95% CI -8.1, -1.4) was found by OHTG status. Both treatments generated similar treatment satisfaction scores, although there was greater weight gain and greater improvement in lipids and liver enzymes after pioglitazone than vildagliptin.ConclusionsComparative glucose-lowering by pioglitazone and vildagliptin is not different between Māori/Pacific people compared with other New Zealand ethnic groups. Presence of OHTG predicts greater glucose lowering by pioglitazone than vildagliptin.Clinical trial registrationwww.anzctr.org.au, identifier (ACTRN12618001907235).https://www.frontiersin.org/articles/10.3389/fendo.2022.1091421/fulldipeptidyl peptidase inhibitorMāoriPacificpioglitazoneprecision medicinestratified drug response |
| spellingShingle | Rebecca Brandon Rebecca Brandon Yannan Jiang Yannan Jiang Rui Qian Yeu Rui Qian Yeu Ry Tweedie-Cullen Ry Tweedie-Cullen Kate Smallman Glenn Doherty Kerry A. Macaskill-Smith Rebekah J. Doran Penny Clark Allan Moffitt Troy Merry Troy Merry Norma Nehren Frances King Jennie Harré Hindmarsh Megan Patricia Leask Megan Patricia Leask Megan Patricia Leask Tony R. Merriman Tony R. Merriman Tony R. Merriman Brandon Orr-Walker Peter R. Shepherd Peter R. Shepherd Ryan Paul Ryan Paul Rinki Murphy Rinki Murphy Stratified glucose-lowering response to vildagliptin and pioglitazone by obesity and hypertriglyceridemia in a randomized crossover trial Frontiers in Endocrinology dipeptidyl peptidase inhibitor Māori Pacific pioglitazone precision medicine stratified drug response |
| title | Stratified glucose-lowering response to vildagliptin and pioglitazone by obesity and hypertriglyceridemia in a randomized crossover trial |
| title_full | Stratified glucose-lowering response to vildagliptin and pioglitazone by obesity and hypertriglyceridemia in a randomized crossover trial |
| title_fullStr | Stratified glucose-lowering response to vildagliptin and pioglitazone by obesity and hypertriglyceridemia in a randomized crossover trial |
| title_full_unstemmed | Stratified glucose-lowering response to vildagliptin and pioglitazone by obesity and hypertriglyceridemia in a randomized crossover trial |
| title_short | Stratified glucose-lowering response to vildagliptin and pioglitazone by obesity and hypertriglyceridemia in a randomized crossover trial |
| title_sort | stratified glucose lowering response to vildagliptin and pioglitazone by obesity and hypertriglyceridemia in a randomized crossover trial |
| topic | dipeptidyl peptidase inhibitor Māori Pacific pioglitazone precision medicine stratified drug response |
| url | https://www.frontiersin.org/articles/10.3389/fendo.2022.1091421/full |
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