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 multi-center 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% female, aged 13.7±2.0 years 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 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%. Co-morbid conditions were common; 18.8% had hypertension, 24.2% had elevated cholesterol, and 6.5% had abnormal liver enzymes. After a median 71 days 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). Change in z-BMI was not significantly different between the two groups, however. Conclusions Most youth with recent onset type 2 diabetes can achieve target HbA1c <8.0% with short-term metformin monotherapy and standard diabetes education.

Presentation and effectiveness of early treatment of type 2 diabetes in youth: lessons from the TODAY study

“…A previous report (7) described changes in HbA1c and BMI during the run-in phase of TODAY, but focused on a comparison of those subjects who could be randomized and those who could not. The goal of the current analysis was to evaluate the effectiveness of initial treatment with metformin and standardized diabetes education in recently diagnosed youth with T2D by examining all subjects who completed the minimum run-in period, whether or not they were randomized.…”

“…Details of screening for TODAY and the run-in phase were previously described (5, 7). Briefly, subjects were identified from the participating pediatric diabetes centers and partners.…”

“…In order to successfully complete run-in, participants were required to demonstrate ≥ 80% medication adherence for at least 6 weeks, tolerate metformin at a dose of at least 500 mg twice daily, miss no more than two run-in visits, maintain a HbA1c of ≤ 8% (64 mmol/mol) for at least 2 months on metformin alone, and demonstrate mastery of basic diabetes education. The run-in period lasted from 2-6 months during which time participants had a minimum of 6 and maximum of 12 visits for mastery of diabetes education (9); the median time in run-in for all those screened was 2.4 months (25 th and 75 th percentiles = 2.0 and 3.0 months, respectively) (7). A total of 228 screened participants (24%) failed to meet criteria for randomization and their characteristics have been previously described (7).…”

“…The run-in period lasted from 2-6 months during which time participants had a minimum of 6 and maximum of 12 visits for mastery of diabetes education (9); the median time in run-in for all those screened was 2.4 months (25 th and 75 th percentiles = 2.0 and 3.0 months, respectively) (7). A total of 228 screened participants (24%) failed to meet criteria for randomization and their characteristics have been previously described (7). The study protocol was approved by the institutional review board of each participating institution.…”

“…Prior to randomization, potential subjects participated in a run-in phase focused on establishing consistent dosing of metformin, delivering standard diabetes education, and weaning insulin in individuals who were receiving it at the time of screening. We previously compared the characteristics of those who successfully completed run-in and those who did not, including change in hemoglobin A1c (HbA1c) and body mass index (BMI) (7). The objectives of the current secondary analyses were to: (1) provide a more complete description of a large geographically and ethnically diverse cohort of youth with recent onset T2D receiving routine clinical care in the US, (2) assess the effect of short-term (8 weeks) standardized diabetes management, including education and treatment with metformin, on clinical and biochemical parameters, and (3) identify potential predictors of improvement in HbA1c and BMI during this short-term intervention.…”