Multiple randomized controlled trials (RCTs) in people with diabetes have demonstrated a substantial placebo effect, as a result of enhanced patient-physician interaction time. In RCTs focused on glycemic control, the non-pharmacological component of clinical inertia was independent of age and presence of microvascular complications. Here we explore if trial participation per se improves metabolic parameters in people with diabetic complications, independent of trial focus. Participants from a clinical development program focusing on progression of diabetic macular edema (DME) randomized to receive either a sham intravitreal injections or laser therapy were pooled. The primary 12-month outcomes were changes in retinal parameters while for this analysis we assessed the least square (LS) mean change in metabolic parameters, HbA1c and fasting plasma glucose (FPG). Participants were stratified by age (<70/≥70 years) and change in eGFR (an internal standard for monitoring disease progression). Participants (n=288, 46% women) had a mean±SD age of 62.9±9.2 years, diabetes and DME durations 12.6±9.0 and 1.5±2.2 years, respectively. The baseline HbA1c was well controlled, 7.4±1.1% and FPG was 8.9±3.3 mmol/l. The mean eGFR was 84.1±25.1 ml/min/1.73m2 and most subjects were at a normotensive target of mean BP 137/78 mmHg. At 12 months, the LS mean HbA1c change ±SEM from baseline was 0.1±0.1 and FPG 0.5±0.2 mmol/l. While no difference was seen between the age groups for HbA1c (0.1% for both), FPG reduction was numerically higher in elderly (0.8 vs. 0.4 mmol/l). The mean decline in eGFR was −6.5±0.8 ml/min/1.73m2 in both age groups. Trial participation per se does not improve metabolic parameters of people with diabetes, where the trial focus is not on metabolic control. This implies providing unfocused time for people with diabetes will not improve metabolic control, suggesting focused consultations between people with diabetes and healthcare providers for management of diabetes.
P.M. Paldánius: Employee; Self; Novartis AG. Stock/Shareholder; Self; Novartis AG. W.D. Strain: Research Support; Self; Bayer AG, Takeda Development Centre Europe Ltd. Speaker's Bureau; Self; NAPP Pharmaceuticals Limited, Novartis AG, Novo Nordisk A/S.