Impact of time to treatment intensification on glycemic goal attainment among patients with type 2 diabetes failing metformin monotherapy

J Diabetes Complications. Nov-Dec 2014;28(6):831-5. doi: 10.1016/j.jdiacomp.2014.06.004. Epub 2014 Jun 19.


Background: Patients with type 2 diabetes on metformin monotherapy frequently require treatment intensification with another anti-hyperglycemic medication over time. Previous studies have indicated that a high proportion of patients with diabetes have a significant delay in the initiation of oral add-on therapy after metformin alone fails to achieve targeted glycemic control. In this study, we evaluated the impact of the timing of treatment intensification with oral add-on drug on glycemic goal attainment among diabetic patients failing metformin monotherapy.

Research design and methods: Using the General Electric (GE) Centricity Electronic Medical Record database (January 2004 through December 2009), we identified 5,870 patients with type 2 diabetes with treatment failure on metformin monotherapy - defined by a glycosylated hemoglobin (HbA1c) of ≥7.5% (index date). This cut-off of ≥7.5% (trigger HbA1c) was chosen rather than that of >7.0% to ensure that selected patients were more likely to be indicated for treatment intensification with add-on drug. Continuous enrollment of one year prior and two years after index date was required to be included in the study. Add-on treatment was defined as prescription of second oral agent from any available therapeutic classes while continuing metformin. Early treatment intensification was defined as initiation of oral add-on therapy within 3 months (n=1,012) of index date while late intensification was defined as add-on initiation between 10 and 15 months after index date (n=461). The study outcome was defined as glycemic goal attainment (HbA1c<7%), which was evaluated between 18 and 24 months after index date.

Results: Our results suggested that at the end of the follow-up period, 47.2% of patients in the early add-on group were at glycemic goal compared to 41.7% in the late add-on group (p=0.039). In a multivariable logistic regression model that accounted for age, gender, trigger HbA1c level, Charlson comorbidity index, anti-hypertensive and anti-hyperlipidemic drug use and history of cardiovascular disease, the adjusted odds ratio (OR) for glycemic goal attainment was 1.36 (95% confidence intervals [CI]: 1.09-1.72) comparing early add-on to late add-on treatment. This association was stronger among patients with higher trigger HbA1c at baseline; ORs of 1.53 (95% CI: 1.08-2.19) for HbA1c ≥8% and 2.63 (95% CI: 1.40-5.27) for HbA1c ≥9%.

Conclusion: These results suggest that earlier use of oral add-on drug in treatment regimen helps better achieve glycemic goal attainment in patients with metformin failure. Future studies should evaluate whether earlier treatment intensification is also associated with longer term health outcomes such as risk of microvascular and macrovascular complications.

Keywords: Diabetes; Failure; Glycemic; Goal; Intensification; Treatment.

MeSH terms

  • Administration, Oral
  • Aged
  • Blood Glucose / metabolism*
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / epidemiology
  • Drug Therapy, Combination / statistics & numerical data
  • Female
  • Glycated Hemoglobin A / metabolism
  • Goals*
  • Humans
  • Hypoglycemic Agents / administration & dosage*
  • Male
  • Metformin / therapeutic use*
  • Middle Aged
  • Retrospective Studies
  • Time-to-Treatment*
  • Treatment Failure


  • Blood Glucose
  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • hemoglobin A1c protein, human
  • Metformin