Treatment Response Between Asian and Non-Asian Patients with Type 2 Diabetes: Similarities and Differences
The global rise in diabetes prevalence has disproportionately affected Asian populations, particularly in China. Asian patients with type 2 diabetes often present distinct physiological characteristics compared to non-Asian populations, including lower body mass index (BMI) at diagnosis, earlier onset of β-cell dysfunction, and genetic predispositions. These differences raise critical questions about whether treatment responses to glucose-lowering therapies vary between ethnic groups. This article synthesizes evidence from meta-analyses, post-hoc analyses, and clinical trials to explore similarities and differences in therapeutic outcomes for Asian and non-Asian patients.
Physiological and Pathological Background
Asian populations exhibit a higher prevalence of type 2 diabetes at lower BMIs than non-Asian populations. This phenomenon is attributed to differences in body composition, with Asians having higher visceral adiposity and lower lean mass for the same BMI. Additionally, Asian patients often demonstrate a more pronounced defect in β-cell function rather than insulin resistance compared to non-Asians. Genetic and pharmacogenetic variations further contribute to potential disparities in drug efficacy and safety. For instance, polymorphisms in drug-metabolizing enzymes and transporters may influence responses to medications such as metformin or sulfonylureas.
Oral Anti-Diabetes Drugs
Alpha-Glucosidase Inhibitors (AGIs)
Meta-analyses comparing AGIs in Asian and non-Asian populations reveal no significant differences in glycemic control or safety outcomes. A meta-analysis of 67 trials found comparable reductions in hemoglobin A1c (HbA1c) (difference: 0.097%, 95% CI: −0.42% to 0.62%, P=0.709), fasting plasma glucose (FPG) (difference: 0.39 mmol/L, 95% CI: −0.40 to 1.19, P=0.318), and postprandial glucose (PPG) (difference: −0.29 mmol/L, 95% CI: −1.80 to 1.22, P=0.692). Weight changes and hypoglycemia incidence were also similar between groups. These findings suggest that AGIs, which delay carbohydrate absorption, are equally effective across ethnicities.
Dipeptidyl Peptidase-4 (DPP-4) Inhibitors
DPP-4 inhibitors demonstrate nuanced differences in efficacy. A meta-analysis reported a greater HbA1c reduction in Asians compared to non-Asians (between-group difference: −0.26%, 95% CI: −0.36% to −0.17%, P<0.001). However, body weight changes after placebo adjustment were comparable (Asians: +0.37 kg; non-Asians: +0.45 kg). A separate study using individual patient data found no significant difference in HbA1c reduction when DPP-4 inhibitors were used as third-line therapy after metformin and sulfonylurea failure. These conflicting results highlight the need for context-specific evaluations, as treatment line and baseline therapies may modulate ethnic-specific responses.
Sodium-Glucose Cotransporter 2 (SGLT2) Inhibitors
SGLT2 inhibitors show similar glucose-lowering effects between Asian and non-Asian patients. A meta-analysis of 56 trials found no significant differences in HbA1c reduction (difference: 0.05%, P>0.05) or weight loss (difference: 0.08 kg, P>0.05). However, Asian patients experienced greater improvements in triglycerides (−0.14 mmol/L vs. non-Asians, P<0.05) and high-density lipoprotein cholesterol (+0.09 mmol/L, P<0.05). These cardiometabolic benefits may reflect ethnic variations in lipid metabolism or adherence to therapy.
Metformin, Sulfonylureas, and Thiazolidinediones (TZDs)
Direct comparisons of metformin, sulfonylureas, and TZDs between ethnic groups are limited. Indirect evidence suggests similarities in HbA1c reduction. For example, Chinese patients treated with metformin achieved HbA1c reductions of −1.84% (normal weight), −1.78% (overweight), and −1.78% (obese), comparable to the −1.12% reduction in Caucasians from the ADOPT trial. Similarly, glibenclamide lowered HbA1c by −0.66% in Chinese patients, aligning with −0.63% in ADOPT. TZDs, such as pioglitazone, reduced HbA1c by −0.67% in Japanese patients, consistent with −0.80% in Caucasians. These parallels suggest that insulin secretagogues and sensitizers may have comparable efficacy across ethnicities despite differences in β-cell function.
Glucagon-Like Peptide-1 Receptor Agonists (GLP-1RAs)
GLP-1RAs exhibit ethnic disparities in glucose-lowering efficacy and hypoglycemia risk. A meta-analysis of 15 trials found greater HbA1c reductions in Asian-dominant studies (between-group difference: −0.32%, 95% CI: −0.64 to −0.01, P=0.04). Weight loss was similar, but hypoglycemia risk was higher in Asians (risk ratio=2.8, 95% CI: 2.3–3.5) compared to non-Asians (risk ratio=1.5, 95% CI: 1.2–1.8). This heightened hypoglycemia risk may relate to stricter glycemic targets in Asian protocols or differences in concomitant therapies.
Insulin Therapy
Insulin regimens yield distinct outcomes between ethnic groups. Post-hoc analyses of insulin lispro mix 75/25 (LM75/25) and insulin glargine (GL) showed smaller HbA1c reductions in Asians (−1.46% vs. −1.84% for LM75/25; −1.25% vs. −1.78% for GL) despite higher insulin doses (LM75/25: 0.63 vs. 0.44 U/kg; GL: 0.47 vs. 0.39 U/kg). Asian patients also experienced less weight gain (LM75/25: +2.6 vs. +3.6 kg; GL: +1.3 vs. +1.9 kg) and lower hypoglycemia rates (15 vs. 23 events/patient-year). These differences may stem from dietary patterns, insulin sensitivity, or adherence to titration protocols.
Limitations and Considerations
Existing evidence has notable limitations. Most studies were post-hoc analyses or meta-analyses not prospectively designed to assess ethnic differences. Confounding factors such as diet, exercise, healthcare access, and socioeconomic status were rarely adjusted for. Additionally, genetic and pharmacogenetic studies remain sparse, limiting mechanistic insights into observed disparities.
Conclusion
Asian and non-Asian patients with type 2 diabetes exhibit both similarities and differences in treatment responses. Oral agents like AGIs, metformin, sulfonylureas, and SGLT2 inhibitors demonstrate comparable efficacy, while DPP-4 inhibitors and GLP-1RAs show modest ethnic variations in glucose-lowering effects. Insulin therapy highlights significant differences in HbA1c reduction, weight gain, and hypoglycemia risk. Clinicians should consider ethnic-specific factors—such as β-cell function, genetic background, and lifestyle—when tailoring treatment plans. Future research should prioritize prospective, ethnically stratified trials to optimize therapeutic strategies for diverse populations.
doi.org/10.1097/CM9.0000000000000012
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