title: A 24-week, prospective, randomized, open-label, treat-to-target pilot study of obese type 2 diabetes patients with severe insulin resistance to assess the addition of exenatide on the efficacy of u-500 regular insulin plus metformin.
abstract: OBJECTIVE
  To compare the efficacy of 500 U/mL (U-500) regular insulin + metformin with U-500 regular insulin + metformin + exenatide in improving glycemic control in patients with severely insulin-resistant type 2 diabetes mellitus (T2DM).
  
  
  METHODS
  Thirty patients with T2DM and severe insulin resistance were screened, and 28 were randomized to regular insulin U-500 + metformin or the GLP-1 analog exenatide, U-500, and metformin. Glycated hemoglobin (HbA1c) levels, body weight, and insulin doses were documented at baseline and at 3 and 6 months. The number and severity hypoglycemic episodes were noted.
  
  
  RESULTS
  There were 7 males and 7 females in each group (U-500 + metformin and U-500 + metformin + exenatide). Overall, U-500 insulin + metformin, either alone or with the addition of exenatide, resulted in a significant improvement in HbA1c in both groups, with no significant difference between the 2 groups. There was no meaningful weight change in those utilizing exenatide. Those on U-500 insulin and metformin alone had a tendency toward some weight gain. No severe hypoglycemia occurred during the study period. Symptomatic hypoglycemia was more common in the group on exenatide, but this occurred in only 5 patients, and the clinical significance of this is uncertain. Insulin dosage changes on U-500 regular insulin were variable but tended to be lower in those subjects on exenatide.
  
  
  CONCLUSIONS
  U-500 regular insulin + metformin is effective for the treatment of T2DM patients with severe insulin resistance. The addition of exenatide may ameliorate potential weight gain but provides no additional improvement in glycemia.
authors.affiliation: Centre for Diabetes and Endocrinology, Johannesburg, South Africa.
authors.forename: Larry A
authors.initials: LA
authors.lastname: Distiller
authors.affiliation: N1 City Medical Chambers, Goodwood, Cape Town, South Africa.
authors.forename: Hendrik
authors.initials: H
authors.lastname: Nortje
authors.affiliation: Helderberg Clinical Trials Centre, Somerset West, South Africa.
authors.forename: Holger
authors.initials: H
authors.lastname: Wellmann
authors.affiliation: Life Chatsmed Garden Hospital and Nelson R Mandela School of Medicine, Durban, South Africa.
authors.forename: Aslam
authors.initials: A
authors.lastname: Amod
authors.affiliation: Kuils River Netcare Hospital, Cape Town, South Africa.
authors.forename: Landman
authors.initials: L
authors.lastname: Lombard