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Randomized Controlled Trial
. 2023 Jan 9:13:1091421.
doi: 10.3389/fendo.2022.1091421. eCollection 2022.

Stratified glucose-lowering response to vildagliptin and pioglitazone by obesity and hypertriglyceridemia in a randomized crossover trial

Rebecca Brandon  1   2 , Yannan Jiang  3   4 , Rui Qian Yeu  1   2 , Ry Tweedie-Cullen  1   2 , Kate Smallman  5 , Glenn Doherty  6 , Kerry A Macaskill-Smith  7 , Rebekah J Doran  7 , Penny Clark  7 , Allan Moffitt  8 , Troy Merry  2   9 , Norma Nehren  10 , Frances King  11 , Jennie Harré Hindmarsh  11 , Megan Patricia Leask  2   12   13 , Tony R Merriman  2   12   13 , Brandon Orr-Walker  14 , Peter R Shepherd  2   15 , Ryan Paul  2   16 , Rinki Murphy  1   2
Affiliations
Randomized Controlled Trial

Stratified glucose-lowering response to vildagliptin and pioglitazone by obesity and hypertriglyceridemia in a randomized crossover trial

Rebecca Brandon et al. Front Endocrinol (Lausanne). .

Abstract

Background: Understanding 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.

Aims: We 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).

Methods: A 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.

Results: 346 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.

Conclusions: Comparative 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 registration: www.anzctr.org.au, identifier (ACTRN12618001907235).

Keywords: Māori; Pacific; dipeptidyl peptidase inhibitor; obesity; pioglitazone; precision medicine; stratified drug response; thiazolidinedione.

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Conflict of interest statement

Authors RP and RM have received speaking honoraria from Lilly, Boehringer Ingelheim, Astra Zeneca, Sanofi, Novo Nordisk, also Novartis (RM) and Inova pharmaceuticals (RP). RP is a member of the Lilly, Novo Nordisk and Dexcom New Zealand advisory boards. Authors KAM, RD, PC were employed by Ventures/Pinnacle Incorporated, a primary health care organisation which has no relevant commercial or financial relationships. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Flow diagram of the study participants included in this analysis.
See this image and copyright information in PMC

References

    1. American Diabetes Association . Pharmacologic approaches to glycemic treatment. Diabetes Care (2021) 44:S111–24. doi: 10.2337/dc21-S009 - DOI - PubMed
    1. Chung WK, Erion K, Florez JC, Hattersley AT, Hivert M-F, Lee CG, et al. . Precision medicine in diabetes: A consensus report from the American diabetes association (ADA) and the European association for the study of diabetes (EASD). Diabetes Care (2020) 43:1617–35. doi: 10.2337/dci20-0022 - DOI - PMC - PubMed
    1. Gan S, Dawed AY, Donnelly LA, Nair ATN, Palmer CAN, Mohan V, et al. . Efficacy of modern diabetes treatments DPP-4i, SGLT-2i, and GLP-1RA in white and Asian patients with diabetes: A systematic review and meta-analysis of randomized controlled trials. Diabetes Care (2020) 43:1948–57. doi: 10.2337/dc19-2419 - DOI - PMC - PubMed
    1. Williams LK, Padhukasahasram B, Ahmedani BK, Peterson EL, Wells KE, Gonzalez Burchard E, et al. . Differing effects of metformin on glycemic control by race-ethnicity. J Clin Endocrinol Metab (2014) 99:3160–8. doi: 10.1210/jc.2014-1539 - DOI - PMC - PubMed
    1. Weng J, Soegondo S, Schnell O, Sheu WH-H, Grzeszczak W, Watada H, et al. . Efficacy of acarbose in different geographical regions of the world: Analysis of a real-life database. Diabetes Metab Res Rev (2015) 31:155–67. doi: 10.1002/dmrr.2576 - DOI - PubMed

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