Efficacy and Safety of Sodium-Glucose Cotransporter 2 Inhibitors in East Asians with Type 2 Diabetes: A Systematic Review and Meta-Analysis

Abstract

IntroductionThe aim of this study was to assess the efficacy and safety of sodium-glucose cotransporter 2 (SGLT2) inhibitors in East Asians with type 2 diabetes mellitus (T2DM).MethodsA literature search that focused primarily on the PubMed, Embase, and Cochrane library databases was performed. All randomized controlled trials (RCTs) which satisfied the inclusion and exculsion criteria were eligible to be included in the meta-analysis. Risk ratios (RRs) and weighted mean differences (WMDs) were used as statistical indicators for the analysis of dichotomous data and continuous outcomes, respectively. Pooled estimates were obtained using random-effects models in RevMan version 5.3.5.ResultsThirty-three RCTs (8496 randomized patients) fulfilled the eligibility criteria for inclusion in the meta-analysis. The meta-analysis showed that, compared with the control group, the use of SGLT2 inhibitors improved both glycated hemoglobin (HbA1c) in patients (WMD − 0.73%; 95% confidence interval [CI] − 0.84, − 0.61) and the percentage of patients with HbA1c < 7% (RR 2.33; 95% CI 1.74, 3.12); lowered both fasting plasma glucose (WMD − 28.47 mg/dl; 95% CI − 32.86, − 24.08) and postprandial glucose (WMD − 52.32 mg/dl; 95% CI − 67.67, − 39.96); reduced body weight (WMD − 1.73 kg; 95% CI − 2.28, − 1.17); and did not increase the risk of hypoglycemia (RR 1.27; 95% CI 0.89, 1.82) and urinary tract infections (RR 0.93; 95% CI 0.68, 1.27). However, SGLT2 inhibitors did increase the risk of genital tract infections (GTIs) (RR 1.73; 95% CI 1.02, 2.96). The stratified analysis showed that patients with higher HbA1c levels at baseline may achieve a greater improvement in HbA1c after taking SGLT2 inhibitors, while those with higher body weight or a longer history of diabetes may have an increased risk of developing GTIs.ConclusionCurrent research suggests that SGLT2 inhibitors have favorable efficacy and safety in East Asian patients with T2DM.Electronic Supplementary MaterialThe online version of this article (10.1007/s13300-019-0674-7) contains supplementary material, which is available to authorized users.

Efficacy and safety of ertugliflozin in East/Southeast Asian patients with type 2 diabetes mellitus

“…A possible explanation for the lower incidence in E/SE Asians compared with non‐E/SE Asians may be that it is in part a result of cultural reporting bias, which was proposed as a possible explanation for similar findings in a study with canagliflozin in Asian patients with T2DM . A recent meta‐analysis of East Asian patients also reported a higher incidence of genital tract infections in those receiving SGLT2 inhibitors compared with the control treatment arms (placebo or non‐SGLT2 inhibitor antihyperglycaemic drugs) . Few patients in the E/SE Asian population had documented hypoglycaemia.…”

Efficacy of Modern Diabetes Treatments DPP-4i, SGLT-2i, and GLP-1RA in White and Asian Patients With Diabetes: A Systematic Review and Meta-analysis of Randomized Controlled Trials

“…In the meta-regression, the percentage of the population who were white and BMI at baseline were associated with HbA 1c reduction, whereas baseline HbA 1c was not correlated. A recent meta-analysis showed that efficacy and safety of SGLT-2i were favorable in East Asian patients with type 2 diabetes ( 13 ). It is interesting to know that SGLT-2i also show greater, albeit nonsignificant, cardiovascular risk reduction in Asians compared with other ethnic groups ( 18 ).…”

“…Where studies were conducted in relatively homogenous populations in Asian countries (e.g., Korea, China, Japan, and Taiwan), we have considered the participants to be in the "Asian" group. We have also followed the definitions of "East Asians" (China, Japan, Mongolia, North Korea, and South Korea) and "South Asians" (Afghanistan, Bangladesh, Bhutan, India, Maldives, Mauritius, Nepal, Pakistan, and Sri Lanka) from previous reports (13,14).…”

Update on the efficacy and safety of sodium–glucose cotransporter 2 inhibitors in Asians and non‐Asians

“…The rate of developing positive colonization and symptomatic vaginitis by the use of SGLT2 inhibitors in women who attended outpatient clinics in Japan appears to be higher in real‐world practice than in clinical trials. Meta‐analysis of the efficacy and safety profiles of SGLT2 inhibitors in East Asian patients with type 2 diabetes showed that the drugs significantly increased the risk of genital tract infection, but did not significantly increase the risk of hypoglycemia, urinary tract infection, hypotension or mortality.…”

“…The major benefits and risks of using SGLT2 inhibitors are listed in Table ; they should be carefully considered for appropriate use of the drugs. Reports regarding the clinical use of SGLT2 inhibitors are accumulating for both Asians and non‐Asians, and are expected to further clarify the risks and benefits of these drugs.…”