Clinical and Genetic Predictors of Secondary Sulfonylurea Failure in Type 2 Diabetes Patients: the Suclingen Study

Abstract

Background: Due to several limitations in the study designs of sulfonylurea pharmacogenomics studies, we investigated the clinical and genetic predictors of secondary sulfonylurea failure in Type 2 diabetes patients. Materials & methods: Patients receiving the maximum sulfonylurea and metformin doses for > year were enrolled. Secondary sulfonylurea failure was defined as HbA1c >7.0% (>53 mmol/mol) after a 12-month follow-up. Results: By multivariate analysis, increased insulin resistance (HOMA2-IR), baseline HbA1c >7.0%, residing in eastern Peninsular Malaysia, and the CC genotype of rs757110 ABCC8 gene polymorphism were independent predictors of secondary sulfonylurea failure (p < 0.05) while sulfonylurea-induced hypoglycemia was protective against such failure (p < 0.05). Conclusion: Sulfonylurea does not benefit patients with an increased risk of secondary sulfonylurea failure.

Keywords::

• ABCC8 gene polymorphism
• insulin resistance
• risk predictors
• secondary failure
• sulfonylurea

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: www.futuremedicine.com/doi/suppl/10.2217/pgs-2019-0171

Author contributions

NK Loganadan designed and conducted the study, analyzed the data and wrote the manuscript. HZ Huri, SR Vethakkan and Z Hussein provided advice regarding study design and manuscript revisions. All authors reviewed and approved the final manuscript. HZ Huri assumed the final responsibility of submitting the manuscript for publication.

Acknowledgments

The authors would like to thank K Chinna from the University of Malaya for his assistance in the statistical analysis. We also appreciate the cooperation of the heads of the out-patient clinics where patients were recruited, in addition to the patients, study nurses and laboratory officers.

Financial & competing interests disclosure

This research was funded by the University of Malaya through the University of Malaya Research Grant (no. RP024-14HTM) and Postgraduate Research Grant (no. PG056-2014A). The funder of the study had no role in the study design, data collection, data analysis, data interpretation, or writing of the report. NK Loganadan, HZ Huri and SR Vethakkan received grants from the University of Malaya during the performance of this study. NK Loganadan also received the Doctor of Philosophy scholarship from Ministry of Health, Malaysia. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

This study was approved by the Medical Research Ethics Committee of the Ministry of Health, Malaysia (approval reference no. (13)KKM/NIHSEC/P14-1055) and the Medical Ethics Committee of University of Malaya Medical Centre (approval reference no. 1059.6). The study was conducted following the principles outlined in the Declaration of Helsinki for all human investigations. In addition, informed consent has been obtained from the participants involved in the investigations involving human subjects.

Additional information

Funding

This research was funded by the University of Malaya through the University of Malaya Research Grant (no. RP024-14HTM) and Postgraduate Research Grant (no. PG056-2014A). The funder of the study had no role in the study design, data collection, data analysis, data interpretation, or writing of the report. NK Loganadan, HZ Huri and SR Vethakkan received grants from the University of Malaya during the performance of this study. NK Loganadan also received the Doctor of Philosophy scholarship from Ministry of Health, Malaysia. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.