Initial Presentation of Type 2 Diabetes in Adolescents Predicts Durability of Successful Treatment with Metformin Monotherapy: Insights from the Pediatric Diabetes Consortium T2D Registry

Abstract

Background/Aims: Many adolescents with type 2 diabetes (T2D) have rapid deterioration of glycemic control on metformin monotherapy within 2 years of diagnosis. Methods: Enrollment data from the Pediatric Diabetes Consortium T2D Registry were used to categorize 276 youth with a T2D duration ≥2 years into two groups: (1) participants with HbA_1c <7.5% on metformin monotherapy (group 1, n = 75) and (2) participants treated with insulin ± metformin (group 2, n = 201). The characteristics of the groups were compared. Results: At enrollment, groups 1 and 2 did not differ in age (16.2 vs. 16.8 years) or BMI percentile (99 vs. 98%); group 2 had higher HbA_1c (9.9% [85 mmol/mol] vs. 5.9% [41 mmol/mol], p < 0.001). Lower HbA_1c and metformin monotherapy at diagnosis were associated with a greater likelihood of adequate control with metformin alone (p < 0.001). In multivariable analysis, HbA_1c at diagnosis (p = 0.001) and diabetes duration (p = 0.009) were associated with adequate control on metformin. The HbA_1c trajectory after diagnosis was worse in group 2. Conclusion: Durable metabolic control of T2D with metformin monotherapy is most likely in youth presenting with lower HbA_1c and with shorter diabetes duration, independent of age, race-ethnicity, and BMI. Elevated HbA_1c levels in those on insulin therapy highlight the importance of early diagnosis and a better understanding of glycemic control barriers.

Eligibility for clinical trials is limited for youth with type 2 diabetes: Insights from the Pediatric Diabetes Consortium T2D Clinic Registry

“…Our findings suggest that patients with HbA1c levels <6.5% (<48 mmol/mol) could be eligible for enrollment in current trials of new drugs for youth with T2D, because superior efficacy of the experimental drug could be demonstrated by preventing the rise in HbA1c levels expected in the majority of well‐controlled patients randomized to the placebo group. Our data also point to the need for future studies of novel approaches to lowering HbA1c levels in very poorly controlled pediatric T2D patients, like supervised administration of long‐acting insulin analogs by school personnel or medically supervised dietary interventions …”

Type 2 Diabetes Mellitus in Adolescents: Should We Reconsider Screening?

“…Bacha et al [1] analyzed the impact of many variables, including metabolic parameters, ethnicity, weight status, and social background, on the outcome of type 2 diabetes mellitus (T2DM) in a large dataset of adolescents. They reported that adolescents with a milder manifestation, only needing treatment with metformin, had a better outcome (defined by HbA1c levels <7.5% four years after diagnosis) than adolescents with a more severe manifestation with initial insulin treatment.…”

“…Most importantly, shorter diabetes duration and lower HbA1c at manifestation were associated with a better outcome [1]. One might argue from a statistical point of view that a milder manifestation is more likely to be mild also in the follow-up.…”

“…However, we know that many adolescents with T2DM – also those treated with metformin alone – have a rapid deterioration of their glycemic control [2, 3]. Therefore, the study by Bacha et al [1] points towards the hypothesis that treating T2DM as early as possible may lead to a better outcome. Nearly half of the patients with a good outcome in this study demonstrated HbA1c levels <7.5% at manifestation, suggesting that they were identified at onset of the disease.…”

“…Since early treatment of T2DM is associated with a better treatment outcome in the analyses of Braha et al [1], this is an important argument for screening for T2DM in high-risk adolescents. Therefore, we should reconsider screening for T2DM, which can be easily performed by HbA1c measurements in pubertal children in high-risk populations [13].…”