Consequences of delaying treatment intensification in type 2 diabetes: evidence from a UK database

Abstract

Objective: Type 2 diabetes mellitus (TD2M) treatment focuses on achieving glycemic control, with HbA1c targeted at 6.5–7.5%. Clinicians commonly delay treatment intensification despite patients failing glycemic targets. This study evaluated longitudinal clinical and cost outcomes in patients failing metformin monotherapy using electronic medical records. Research design and methods: Adults with incident T2DM were identified in the UK Clinical Practice Research Datalink (CPRD) from 1 January 2000 to 31 March 2014. Patients were initiated on metformin monotherapy but had not reached target (HbA1c <7%). Patients were grouped by time to intensification of second-line therapy from first recorded HbA1c ≥7%: Group A, rapid intensification within 365 days; Group B, delayed intensification days 366–1824; Group C, never intensified. Patients were followed from day 366 for 5 years until end of study, switch to insulin, migration or death. Main outcome measures: The study evaluated baseline clinical and medication characteristics which were re-evaluated each year, including HbA1c, weight, cholesterol and concomitant prescribing. Results: A total of 6710 patients were included (Group A 2647, Group B 2452, Group C 1611). Group A achieved a significant decline in HbA1c at 1 year post-index date compared to Groups B and C (−1.13% Group A; +0.26% Group B, +0.16% Group C). A significantly higher proportion of patients achieved HbA1c target < 7% in Group A (Group A [45.8%]; Group B [19.1%], p < 0.0001). Using an adjusted hazard model, Group A was found to achieve the HbA1c target from the index date significantly faster than Group B (hazard ratio 3.25 [95% CI 2.87–3.69]). The most commonly prescribed second-line medications were sulfonylureas in Groups A and B throughout observation and were associated with significant weight gain (+1.3 kg per patient) in the adjusted models. Conclusions: Patients who were rapidly intensified achieved a maintained reduction in HbA1c faster than those with delayed intensification or no second-line therapy, despite a higher baseline HbA1c.

Keywords:

• Diabetes
• epidemiology
• hyperglycemia
• intensification
• metformin

Transparency

Declaration of funding

This work was fully funded by MSD UK.

Author contributions: L.W. developed the study protocol, conducted the analyses with R.F. and developed the manuscript. R.D. and H.L. contributed to the study protocol and manuscript. R.F. conducted analyses and contributed to protocol planning and manuscript preparation. A.H.B. contributed to study and protocol design, reviewed data and contributed to manuscript preparation.

Declaration of financial/other relationships

L.W. has disclosed that she is an epidemiological consultant to MSD and was fully funded by them to conduct this study; L.W. additionally consults for a variety of other pharmaceutical companies. R.F. has disclosed that she was the senior statistician for the project, working for Explore-Epi. R.D. and H.L. have disclosed that they are full time employees of MSD UK Ltd with no other interests or shareholdings. A.H.B. has disclosed that he has received honoraria for lectures and advisory work from MSD, Novartis, B-I, Astra-Zeneca, Janssen, Takeda, Eli Lilly, Novo Nordisk and Sanofi-Aventis.

CMRO peer reviewer 1 has received consulting and/or speaker fees from Eli Lilly, Sanofi, Novo Nordisk, Glaxo-Smith-Kline, Taisho Pharmaceutical, Astellas Pharma, BD, Boehringer Ingelheim, Johnson & Johnson and Takeda; and clinical commissioned/joint research grants from Boehringer Ingelheim, Eli Lilly and MSD. CMRO peer reviewers 2 and 3 have no relevant financial or other relations to disclose.

Acknowledgments

The authors thank Dr. Aiden Flynn for his contribution to the statistical analysis of this study.