Metformin monotherapy in youth with recent onset type 2 diabetes: experience from the prerandomization run-in phase of the TODAY study

Abstract

Background: TODAY (Treatment Options for type 2 Diabetes in Adolescents and Youth) is a federally funded multicenter randomized clinical trial comparing three treatments of youth onset type 2 diabetes.

Objective: To describe the experience of youth participating in a 2-6 month run-in period in preparation for randomization into TODAY.

Subjects: An ethnically diverse sample of 927 youth, 65.4% females, aged 13.7 ± 2.0 yr old, with type 2 diabetes for a median of 2 months (0.7-7.8 months, 25th-75th percentiles).

Methods: A run-in period was conducted to achieve HbA1c <8% with metformin monotherapy and diabetes education, and to evaluate adherence to pill taking, visit attendance, and other procedures.

Results: At entry, mean body mass index (BMI) and z-BMI were 35.6 ± 7.7 and 2.3 ± 0.4, respectively, mean HbA1c was 7.7 ± 2.2%, only 42.5% were on a hypoglycemic treatment, and 35.6% had HbA1c ≥8%. Comorbid conditions were common; 18.8% had hypertension, 24.2% had elevated cholesterol, and 6.5% had abnormal liver enzymes. After a median 71 d of run-in, 90.9% had HbA1c <8%, 77.9% had HbA1c <7%, and 46.4% had HbA1c <6%. Of the 772 youth achieving the target HbA1c <8%, 704 (91.2%) were randomized; non-adherence to metformin treatment was the main cause for non-randomization. Youth proceeding to randomization decreased weight by 0.68 kg and HbA1c by 1.45% compared to a weight gain of 0.71 kg and HbA1c decrease of 0.74% in the non-randomized youth (p = 0.01 in both cases). However, change in z-BMI was not significantly different between the two groups.

Conclusions: Most youth with recent onset type 2 diabetes can achieve target HbA1c <8.0% with short-term metformin monotherapy and standard diabetes education (ClinicalTrials.gov identifier: NCT00081328).

Figure 1. Distribution of Change in Weight and HbA1c of Participants during Run-in (Pre-Randomization Phase) of TODAY

Figure 1A. The 704 participants who met all randomization criteria, including HbA1c <8% on metformin monotherapy, experienced significantly more weight loss than the 223 who did not meet criteria. Six participants lost >10 kg (5 among the successes and 1 among the failures). Figure 1B. A greater proportion of the 704 participants who met all randomization criteria, including HbA1c <8% on metformin monotherapy, experienced a decline in HbA1c compared with the 223 who did not meet criteria. Eleven participants had HbA1c decline by >7% during run-in (8 among the successes and 3 among the failures).