Delay of insulin addition to oral combination therapy despite inadequate glycemic control: delay of insulin therapy

J Gen Intern Med. 2007 Apr;22(4):453-8. doi: 10.1007/s11606-007-0139-y.


Background: Patients and providers may be reluctant to escalate to insulin therapy despite inadequate glycemic control.

Objectives: To determine the proportion of patients attaining and maintaining glycemic targets after initiating sulfonylurea and metformin oral combination therapy (SU/MET); to assess insulin initiation among patients failing SU/MET; and to estimate the glycemic burden incurred, stratified by whether HbA(1c) goal was attained and maintained.

Design: Longitudinal observational cohort study.

Subjects: Type 2 diabetes patients, 3,891, who newly initiated SU/MET between 1 January 1996 and 31 December 2000.

Measurements: Subjects were followed until insulin was added, health plan disenrollment, or until 31 December 2005. We calculated the number of months subjects continued SU/MET therapy alone, in total, and during periods of inadequate glycemic control; the A1C reached during those time periods; and total glycemic burden, defined as the estimated cumulative monthly difference between measured A1C and 8%.

Results: During a mean follow-up of 54.6 +/- 28.6 months, 41.9% of the subjects added insulin, and 11.8% received maximal doses of both oral agents. Over half of SU/MET patients attained but failed to maintain A1C of 8%, yet continued SU/MET therapy for an average of nearly 3 years, sustaining glycemic burden equivalent to nearly 32 months of A1C levels of 9%. Another 18% of patients never attained the 8% goal with SU/MET, yet continued that therapy for an average of 30 months, reaching mean A1C levels of 10%.

Conclusions: Despite inadequate glycemic control, a minority of patients added insulin or maximized oral agent doses, thus, incurring substantial glycemic burden on SU/MET. Additional studies are needed to examine the benefits of rapid titration to maximum doses and earlier initiation of insulin therapy.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Aged
  • Blood Glucose / drug effects
  • Blood Glucose / metabolism
  • Cohort Studies
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / drug therapy
  • Drug Therapy, Combination
  • Female
  • Follow-Up Studies
  • Glycemic Index / drug effects*
  • Glycemic Index / physiology
  • Humans
  • Hypoglycemic Agents / administration & dosage*
  • Insulin / administration & dosage*
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Retrospective Studies
  • Time Factors


  • Blood Glucose
  • Hypoglycemic Agents
  • Insulin