Response to Letter to the Editor Regarding OpT2mise Study

Dear Editor:

The Macedonian National Diabetes Committee ¹ has reported that 13 patients who had met criteria for enrollment in the OpT2mise study have subsequently claimed they have type 1 diabetes, in the context of seeking funding for their diabetes supplies from the national healthcare insurer. We disagree with the Committee's subsequent comment expressing concern that large numbers of patients with type 1 diabetes were enrolled into the OpT2mise study at the Macedonian investigator site.

Given the complexity of the diagnosis of type 2 diabetes (T2D) in patients who are insulin-requiring, the eligibility criteria for the OpT2mise study were developed by a panel of international endocrinologists who met in Vienna on September 30, 2009 for the first OpT2mise Advisory Board. As a result of this deliberation, the diagnosis of T2D in the OpT2mise study was based on both documented insulin resistance and a historical clinical diagnosis of T2D by the investigator. In addition, further insulin up-titration was required during the run-in phase to reach a minimum dose of 0.7 U/kg/day, which is typically higher than insulin dosing requirements of patients with type 1 diabetes. The Vienna Expert Panel decided not to exclude patients demonstrating anti–glutamic acid decarboxylase antibodies who otherwise met the criteria of insulin-resistant T2D, an approach similarly used in previous large trials. For example, 11.6% of the United Kingdom Prospective Diabetes Study cohort was anti–glutamic acid decarboxylase positive, and these patients were not excluded from the study analyses. ²

In the OpT2mise study, patients who enrolled at the Macedonian investigator site had met the study's eligibility criteria and had a historical diagnosis of T2D verified by the investigator. We can further confirm, considering patients' insulin resistance, metabolic syndrome (hypertension, high level of triglycerides, low level of high-density lipoprotein), age of onset, duration of diabetes, insulin dose, and C-peptide and anti–glutamic acid decarboxylase antibodies, that there is ample evidence that the patients from Macedonia were appropriately enrolled based on the inclusion criteria for T2D in the OpT2mise study.

Separately, since then we have performed a sensitivity analysis, excluding all patients from Macedonia, which found no significant effect on the overall primary study end point.

Finally, we cannot comment on the clinical information that was submitted individually by patients to the Macedonian National Diabetes Committee for funding purposes.