title: Long-term glycaemic efficacy and weight changes associated with thiazolidinediones when added at an advanced stage of type 2 diabetes.
abstract: OBJECTIVE
  To describe the outcome of 35 patients with type 2 diabetes prospectively followed for 6 years after the addition of a thiazolidinedione (TZD) to a failing regimen of a sulphonylurea and metformin -- triple oral therapy.
  
  
  METHODS
  Study patients were assessed for the need for the addition of insulin to their regimen, and follow-up clinical and laboratory findings were analysed.
  
  
  RESULTS
  At a mean follow-up of 72 +/- 1.5 months (range 53-80), 18 (51%) of patients remained well controlled on triple oral therapy with a mean glycosylated haemoglobin (HbA1c) value of 6.9 +/- 0.2% (upper limit of normal 6.2%). In 17 other patients, triple oral therapy failed and the use of insulin was necessary after a mean duration of 38 (range 18-68) months. The mean HbA1c in these patients was 8.0 +/- 0.3%. The group that was maintained on triple oral therapy gained 15.2 +/- 1.9 lbs over the 6-year study which was significantly higher than the baseline weight. Alternatively, the group that failed and had insulin added to their therapy gained 20.2 +/- 4.5 lbs over the same period which was also significantly different from baseline but not from the triple oral therapy group. Although after 3 years a trend towards weight loss occurred in the triple oral therapy group, the insulin-added group continued to gain weight. Stimulated C-peptide levels increased significantly in the triple therapy group from 3.6 +/- 0.9 to 4.3 +/- 1.2 ng/ml and had not increased or decreased non-significantly from 3.7 +/- 0.8 to 3.2 +/- 0.6 ng/ml at the time of insulin initiation in the insulin-requiring group.
  
  
  CONCLUSIONS
  When used late in the course of type 2 diabetes, TZDs result in improved and prolonged glycaemic control which persisted for a median time of 6 years. Weight gain with TZDs peaks and then plateaus (and even trends downwards) at 3 years, although the addition of insulin to a failing oral therapy regimen results in a further and continuing weight gain in spite of inferior glycaemic control. Continuing glycaemic control with triple oral therapy is dependent on preservation or augmentation of endogenous insulin production.
authors.affiliation: The University of Alabama at Birmingham School of Medicine, Birmingham, AL 35294, USA. dshbell@uab.edu
authors.forename: D S H
authors.initials: DS
authors.lastname: Bell
authors.forename: F
authors.initials: F
authors.lastname: Ovalle
mesh_terms: D000284:Administration, Oral; D001786:Blood Glucose / Q000032:analysis*; D002096:C-Peptide / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D004359:Drug Therapy, Combination; D005500:Follow-Up Studies; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage*; D007267:Injections; D007328:Insulin / Q000008:administration & dosage; D007333:Insulin Resistance; D008134:Long-Term Care / Q000379:methods; D008687:Metformin / Q000008:administration & dosage; D008875:Middle Aged; D013453:Sulfonylurea Compounds / Q000008:administration & dosage; D045162:Thiazolidinediones / Q000008:administration & dosage*; D017211:Treatment Failure; D016896:Treatment Outcome; D015430:Weight Gain / Q000187:drug effects*
chemical_list: D001786:Blood Glucose; D002096:C-Peptide; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D008687:Metformin; D013453:Sulfonylurea Compounds; D045162:Thiazolidinediones