TY - JOUR
T1 - Effect of race on the glycaemic response to sitagliptin
T2 - Insights from the Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS)
AU - for the TECOS Study Group
AU - Davis, Timothy M.E.
AU - Mulder, Hillary
AU - Lokhnygina, Yuliya
AU - Aschner, Pablo
AU - Chuang, Lee Ming
AU - Raffo Grado, Carlos A.
AU - Standl, Eberhard
AU - Peterson, Eric D.
AU - Holman, Rury R.
N1 - Funding Information:
Funding for this research was provided by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, New Jersey.
Funding Information:
T. M. E. D. is supported by a National Health and Medical Research Council of Australia Practitioner Fellowship. R. R. H. is an NIHR Senior Investigator. T. M. E. D. has received grants and personal fees from AstraZeneca, Merck, Boehringer-Ingelheim and Novartis. Y. L. has received grants from Merck, Janssen Research & Development, AstraZeneca, GlaxoSmithKline and Bayer HealthCare AG. P. A. has received grants and personal fees from AstraZeneca, Boehringer Ingelheim, Eli Lilly, GlaxoSmithKline, Janssen, Merck, Sharpe & Dohme, Takeda, Novartis and Sanofi. E. S. has received personal fees from Oxford Diabetes Trials Unit, AstraZeneca, Bayer, Boehringer-Ingelheim, Merck Serono-Excemed, Novartis, NovoNordisk and Sanofi. E. D. P. has received grants and personal fees from AstraZeneca, Merck and Sanofi. R. R. H. has received grants and personal fees from Merck Sharp & Dohme, grants from AstraZeneca, grants and personal fees from Bayer, personal fees from Novartis, grants and personal fees from Boehringer Ingelheim, personal fees from Amgen and Servier, and other support from Elcelyx, GlaxoSmithKline, Janssen and Takeda. H. M., L-M. C. and C. A. R. G. have no disclosures. T. M. E. D. was a local TECOS investigator, conceived this sub-study and produced the first draft of the manuscript. H. M. performed statistical analyses and reviewed/edited the manuscript. Y. L. performed statistical analyses and reviewed/edited the manuscript. P. A. was a country lead investigator, member of the TECOS Operations Committee and reviewed/edited the manuscript. L-M. C was a country lead investigator, member of the TECOS Operations Committee and reviewed/edited the manuscript. C. A. R. G. was a country lead investigator, member of the TECOS Operations Committee and reviewed/edited the manuscript. E. S. was a member of the TECOS Executive Committee and reviewed/edited the manuscript. E. D. P. was Joint Chair of the TECOS Executive Committee and reviewed/edited the manuscript. R. R. H. was Joint Chair of the TECOS Executive Committee and reviewed/edited the manuscript.
Funding Information:
T. M. E. D. is supported by a National Health and Medical Research Council of Australia Practitioner Fellowship. R. R. H. is an NIHR Senior Investigator.
Publisher Copyright:
© 2018 John Wiley & Sons Ltd
PY - 2018/6
Y1 - 2018/6
N2 - Aim: Pooled efficacy studies suggest that glycaemic responses to dipeptidyl-peptidase 4 inhibitors in type 2 diabetes are greatest in Asians, who may also respond better to alpha-glucosidase inhibitors. We assessed the glycaemic impact of sitagliptin by race in the Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS), and whether this was enhanced in Asians with concomitant acarbose therapy. Materials and methods: TECOS enrolled 14 671 patients with type 2 diabetes, cardiovascular disease and HbA1c of 48–64 mmol/mol (6.5%-8.0%), and randomized them, double-blind, to sitagliptin or placebo. There were 3265 patients (22.3%) from Asian countries. Background glucose-lowering therapies were unaltered for the first 4 months post randomization unless clinically essential, facilitating comparison of sitagliptin-associated effects in self-identified East Asian, Other (South) Asian, White Caucasian, Hispanic, Black and Indigenous groups. Results: Median baseline HbA1c by race was 54 to 57 mmol/mol (7.1%-7.4%). Mean 4-month reduction in placebo-adjusted HbA1c was greatest in East Asians (−6.6 mmol/mol [−0.60%] vs ≤6.0 mmol/mol [≤0.55%] in other groups), with significantly greater reduction vs the 2 largest groups (White Caucasians, Other Asians; P <.0001) after adjustment for covariates. After the first 4 months, East and Other Asians were more likely to initiate additional oral therapy (metformin and/or sulfonylureas) than insulin vs White Caucasians (P <.0001). Acarbose use increased in the Asian patients, but no glycaemic interaction with allocated study medication was observed (adjusted P =.12). Conclusions: The greatest initial reduction in HbA1c with sitagliptin in the TECOS population was in East Asians. No enhanced glycaemic effect was seen when sitagliptin was given with acarbose.
AB - Aim: Pooled efficacy studies suggest that glycaemic responses to dipeptidyl-peptidase 4 inhibitors in type 2 diabetes are greatest in Asians, who may also respond better to alpha-glucosidase inhibitors. We assessed the glycaemic impact of sitagliptin by race in the Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS), and whether this was enhanced in Asians with concomitant acarbose therapy. Materials and methods: TECOS enrolled 14 671 patients with type 2 diabetes, cardiovascular disease and HbA1c of 48–64 mmol/mol (6.5%-8.0%), and randomized them, double-blind, to sitagliptin or placebo. There were 3265 patients (22.3%) from Asian countries. Background glucose-lowering therapies were unaltered for the first 4 months post randomization unless clinically essential, facilitating comparison of sitagliptin-associated effects in self-identified East Asian, Other (South) Asian, White Caucasian, Hispanic, Black and Indigenous groups. Results: Median baseline HbA1c by race was 54 to 57 mmol/mol (7.1%-7.4%). Mean 4-month reduction in placebo-adjusted HbA1c was greatest in East Asians (−6.6 mmol/mol [−0.60%] vs ≤6.0 mmol/mol [≤0.55%] in other groups), with significantly greater reduction vs the 2 largest groups (White Caucasians, Other Asians; P <.0001) after adjustment for covariates. After the first 4 months, East and Other Asians were more likely to initiate additional oral therapy (metformin and/or sulfonylureas) than insulin vs White Caucasians (P <.0001). Acarbose use increased in the Asian patients, but no glycaemic interaction with allocated study medication was observed (adjusted P =.12). Conclusions: The greatest initial reduction in HbA1c with sitagliptin in the TECOS population was in East Asians. No enhanced glycaemic effect was seen when sitagliptin was given with acarbose.
KW - ethnicity
KW - glycaemic control
KW - sitagliptin
KW - type 2 diabetes
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U2 - 10.1111/dom.13242
DO - 10.1111/dom.13242
M3 - Article
C2 - 29405540
AN - SCOPUS:85042521916
SN - 1462-8902
VL - 20
SP - 1427
EP - 1434
JO - Diabetes, Obesity and Metabolism
JF - Diabetes, Obesity and Metabolism
IS - 6
ER -