Insulin 70/30 Mix Plus Metformin Versus Triple Oral Therapy in the Treatment of Type 2 Diabetes After Failure of Two Oral Drugs

Abstract

OBJECTIVE -Subjects (n ϭ 188) with type 2 diabetes and inadequate response to two oral medications (A1C Ͼ8.0%) were randomly assigned to treatment with either a third oral medication or an insulin 70/30 mix b.i.d. plus metformin for a comparison of efficacy, safety, and cost.RESEARCH DESIGN AND METHODS -The protocol called for aggressive dose titration to achieve target values of fasting blood glucose (80 -120 mg/dl), postprandial glucose (Ͻ160 mg/dl), and A1C (Ͻ7%). These efficacy parameters were evaluated at weeks 2, 6, 12, and 24 of therapy. If dose adjustments failed to achieve targeted glycemic control, subjects were switched to an alternate therapy.RESULTS -At the end of study (week 24 of therapy), A1C and fasting plasma glucose (FPG) values showed comparable decreases in the two treatment groups. Only 31% (oral therapy) and 32% (insulin plus metformin) of subjects achieved target values of A1C (Ͻ7%). A total of 10 of the 98 subjects randomized to triple oral therapy (10.2%) who failed to improve sufficiently were switched to insulin therapy. An additional four subjects dropped out of the oral treatment group due to adverse events felt to be potentially drug related. Only two of the subjects randomized to insulin plus metformin had to be switched to basal-bolus regimens (regular insulin and NPH insulin). Cost analysis determined that insulin plus metformin (mean cost $3.20/day) provided efficacy equal to that of a triple oral drug regimen ($10.40/day).CONCLUSIONS -Insulin 70/30 mix plus metformin was as effective as triple oral therapy in lowering A1C and FPG values. The triple oral regimen was not as cost effective, and a high percentage of subjects (total of 16.3%) did not complete this regimen due to lack of efficacy or side effects.

Management of hyperglycaemia in type 2 diabetes: a consensus algorithm for the initiation and adjustment of therapy

“…1). When HbA 1c is close to goal (<8.0%), addition of a third oral agent could be considered; however, this approach is relatively more costly and potentially not as effective in lowering glycaemia compared with adding or intensifying insulin [72]. Intensification of insulin therapy usually consists of additional injections that might include a shortor rapid-acting insulin given before selected meals to reduce postprandial glucose excursions (Fig.…”

A comparison of twice-daily exenatide and biphasic insulin aspart in patients with type 2 diabetes who were suboptimally controlled with sulfonylurea and metformin: a non-inferiority study

“…In addition, a fear of hypoglycaemic episodes or pronounced increases in body weight may have precluded the use of higher insulin doses. It should also be considered that all patients in the current trial remained on both metformin and sulfonylurea, whereas in the previous premixed insulin trials, metformin and sulfonylurea therapy were stopped [27] or only metformin was continued [20,26,28]. Certainly, a notable strength of the present study is the long duration.…”

“…The question arises of whether the titration of insulin doses should have been more aggressive, potentially leading to better glycaemic control. Investigators in the current trial were encouraged to titrate insulin doses as high as clinically possible, yet the daily insulin doses at endpoint, as well as the proportion of patients who achieved a target HbA 1c of ≤7.0%, were generally lower than in previous studies of premixed insulin preparations [20,[26][27][28]. In addition to biases intrinsic to open-label studies [29], multiple factors could have influenced the comparatively low endpoint mean insulin dose observed in this trial.…”

Medical management of hyperglycaemia in type 2 diabetes mellitus: a consensus algorithm for the initiation and adjustment of therapy

“…When insulin injections are started, insulin secretagogues (sulfonylurea or glinides) should be discontinued, or tapered and then discontinued, since they are not considered to be synergistic. Although addition of a third oral agent can be considered, especially if the HbA 1c level is close to target (HbA 1c <8.0%), this approach is usually not preferred as it is no more effective in lowering glycaemia, and is more costly, than initiating or intensifying insulin [91].…”