Differences in the glucose-lowering efficacy of dipeptidyl peptidase-4 inhibitors between Asians and non-Asians: a systematic review and meta-analysis

Abstract

Aims/hypothesis The aim of this work was to compare the glucose-lowering efficacy of dipeptidyl peptidase-4 (DPP-4) inhibitors between Asian and non-Asian patients with type 2 diabetes. Methods We searched MEDLINE, EMBASE, LILACS, CENTRAL, ClinicalTrials.gov and conference proceedings. Studies were eligible if they were randomised controlled trials with a treatment duration of at least 12 weeks, compared a DPP-4 inhibitor with a placebo as either monotherapy or oral combination therapy, had information on ethnicity and HbA 1c values and were published or described in English. A systematic review and meta-analysis with a meta-regression analysis was conducted. Results Among 809 potentially relevant studies, 55 trials were included. A meta-analysis revealed that DPP-4 inhibitors lowered HbA 1c to a greater extent in studies with ≥50% Asian participants (weighted mean difference [WMD] −0.92%; 95% CI −1.03, −0.82) than in studies with <50% Asian participants (WMD −0.65%; 95% CI −0.69, −0.60). The between-group difference was −0.26% (95% CI −0.36, −0.17, p<0.001). The baseline BMI significantly correlated with the HbA 1c -lowering efficacy of DPP-4 inhibitors. The RR of achieving the goal of HbA 1c <7.0% (53.0 mmol/mol) was higher in studies with ≥50% Asian participants (3.4 [95% CI 2.6, 4.7] vs 1.9 [95% CI 1.8, 2.0]). The fasting plasma glucose-lowering efficacy was higher with monotherapy in the Asiandominant studies, but the postprandial glucose-lowering efficacy and changes in body weight were comparable between the two groups. Conclusions/interpretation DPP-4 inhibitors exhibit a better glucose-lowering efficacy in Asians than in other ethnic groups; this requires further investigation to understand the underlying mechanism, particularly in relation to BMI.

Safety and efficacy of teneligliptin in Japanese patients with type 2 diabetes mellitus: a pooled analysis of two Phase III clinical studies

“…HbA 1c was significantly lower at week 52 than at baseline in all groups. DPP-4 inhibitors have a neutral or positive effect on bodyweight [14,15]. We observed a tendency toward weight gain of 0.3 --0.5 kg with monotherapy or combination therapy with a sulfonylurea or glinide at the end of 52 weeks; these differences, albeit small, were statistically significant at the end of 52 weeks.…”

“…Overall, there were no clinically significant changes in bodyweight throughout the 52-week period in any groups. Previous studies have shown that higher baseline HbA 1c , lower BMI and shorter duration of diabetes are related to reductions in HbA 1c when using DPP-4 inhibitors in T2DM patients [14,19]. Teneligliptin also produced greater HbA 1c reductions with higher baseline HbA 1c , and slightly improved HbA 1c in patients with lower BMI (< 25 kg/m 2 ), although these patients had lower baseline HbA 1c compared with patients with BMI ‡ 25 kg/m 2 (7.83 ± 0.73 vs 7.94 ± 0.81%, respectively).…”

“…Completed n = 68 Differences in the efficacy of DPP-4 inhibitors have been observed between Asian and non-Asian or Japanese and non-Japanese patients [14,15]. Because of these observed differences between populations, data from Japanese patients are important to evaluate the utility of DPP-4 inhibitors in the Japanese setting.…”

Relationship between deterioration of glycated hemoglobin‐lowering effects in dipeptidyl peptidase‐4 inhibitor monotherapy and dietary habits: Retrospective analysis of Japanese individuals with type 2 diabetes

“…Previous studies have shown that DPP4is exert greater glycated hemoglobin (HbA1c)‐lowering effects (HLE) in East Asians3, 4. This enhanced efficacy has been attributed to the unique type 2 diabetes phenotype in East Asians, who tend to be non‐obese and to show β‐cell dysfunction2, 5.…”

Once-weekly DPP-4 inhibitors: do they meet an unmet need?

“…This study also reported better efficacy of omarigliptin once weekly than placebo and non-inferiority versus sitagliptin once daily ( Table 1). The results of these two studies obtained in Japanese patients should be replicated in other ethnic groups, especially because DPP-4 inhibitors were shown to exhibit a better glucose-lowering efficacy in Asian than in Caucasian people and because doses of DPP-4 inhibitors may also differ 9 .…”