Comparison of Placebo Effect between Asian and Caucasian Type 2 Diabetic Patients: A Meta-Analysis

Background: Placebo was defined as any therapy that is used for its nonspecific psychological and physiologic effect but has no specific pharmacologic impact on the condition being treated. Besides medication therapies, studies have found that the optimal dietary approach as well as physical activity and education are useful to control hyperglycemia in patients with type 2 diabetes (T2DM). The aim of this study was to evaluate the placebo effects of antidiabetic therapies in Asian and Caucasian T2DM patients and make a comparison between the two ethnicities. Methods: A search using the MEDLINE database, EMBASE, and Cochrane Database was performed, from when recording began until December 2016. The main concepts searched in English were sulfonylurea (SU); alpha glucosidase inhibitors (AGI); metformin (MET); thiazolidinediones (TZD); dipeptidyl peptidase-4 inhibitors (DPP-4i); sodium-glucose cotransporter 2 inhibitors (SGLT2i); glucagon-like peptide-1 receptor agonist (GLP-1RA); type 2 diabetes (T2DM); placebo controlled; and randomized controlled trials. Using the Cochrane instrument, we evaluated the adequacy of randomization, allocation concealment procedures, and blinding. Results: This study included 63 studies with a total of 7096 Asian patients involved and 262 studies with a total of 27,477 Caucasian patients involved. In Caucasian population, the use of placebo led to significant reductions of glycosylated hemoglobin (HbA1c), −0.683% (P = 0.008) in SU monotherapy treatment, −0.193% (P = 0.001) in DPP-4i treatment, and −0.230% (P < 0.001) in SGLT2i treatment, respectively. In Asian population, the use of placebo resulted in significant decreases of HbA1c, −0.162% (P = 0.012) in DPP-4i treatment and −0.269% (P = 0.028) in GLP-1RA add-on therapy, respectively. The placebo also significantly reduced body weight. In Caucasian population, placebo use resulted in 0.833 kg (P = 0.006) weight loss by SU treatment and 0.953 kg (P = 0.006) weight loss by GLP-1RA treatment. In Asian population, the placebo led to a weight change of 0.612 kg (P < 0.001) by GLP-1RA analog treatment. The changes of HbA1c and weight due to the placebo effect in other treatments were not significant in both Asian and Caucasian population. Comparisons of the placebo effect on HbA1c change and weight change in each treatment group indicated that no significant difference was found between Asian and Caucasian population. Conclusions: The overall differences of the placebo effect on HbA1c changes as well as on body weight changes were not significant between Asian and Caucasian T2DM patients. The placebo effect on HbA1c changes and weight changes was not associated with baseline age, gender, baseline body mass index, baseline HbA1c, duration of diabetes, or study duration