Filling the Knowledge Gap in Diabetes Management During Ramadan: the Evolving Role of Trial Evidence.

UNLABELLED: Muslim patients with type 2 diabetes (T2D) who fast during Ramadan face challenges in diabetes management due to substantial alterations in lifestyle and treatment that frequently accompany the decision to fast. International guidelines for treating T2D do not fully address the clinical issues unique to fasting, and other guidance documents lack the large and high-quality evidence base available for non-fasting conditions. We reviewed 10 randomized controlled trials and 20 observational studies in T2D during Ramadan to assess the quality of evidence and identify issues in trial design that should be addressed in future studies. Results indicated that heterogeneity in key aspects of trial design precluded meaningful comparisons across studies. These included patients' baseline treatment at entry; use of a cutoff for glycemic control [glycated hemoglobin (HbA1c)] for eligibility; exclusion of patients with a history of recurrent hypoglycemia or hypoglycemia unawareness, or with other serious systemic diseases; duration of treatment and follow-up, selection of safety versus efficacy as primary end point; and definition and measurement of those end points. Fructosamine was rarely used as an efficacy end point, despite the advantage of reflecting glycemic control over a period more closely aligned with the duration of Ramadan fasting than HbA1c. Adherence to treatment, definition and adherence to fasting, and changes in diet and exercise were reported inconsistently, and when reported, not in a fashion that would allow adequate control of confounding due to these variables. Despite a large body of evidence demonstrating their safety and efficacy in non-fasting populations, only two trials reported data for glucagon-like peptide-1 analogs, and neither involved a head-to-head comparison against dipeptidyl peptidase-4 inhibitors. More rigorous studies using trial designs suited to the unique conditions of a fasting population and capturing both standardized efficacy and safety end points are needed to provide better guidance to optimal treatment of T2D during Ramadan fasting.

FUNDING: Novo Nordisk AG.