GLP-1 Receptor Agonists for Obesity in Asians: Evidence From East Asia and Research Gaps in South Asia
Year: 2025
Type: article
Abstract: Dear Editor, Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have redefined obesity management, offering weight reductions previously achievable only with bariatric surgery. Given ethnic differences in adiposity and cardiovascular (CV) risk, it is critical to evaluate whether Asians derive similar or greater benefit compared with Caucasians. The SLIMMER trial represents the most recent addition to obesity randomized controlled trials (RCTs) in Asian populations, the first phase 3 study of ecnoglutide, a novel cyclic adenosine monophosphate-biased GLP-1RA, conducted exclusively in China. At 48 weeks, ecnoglutide produced –9.9% (1.2 mg), –13.3% (1.8 mg), and –15.4% (2.4 mg) mean weight loss from baseline, compared with –0.3% with placebo (placebo-adjusted –9.6% to –15.1%), with 78%–93% of participants achieving ≥5% weight reduction. Efficacy was consistent across sex, baseline body mass index (BMI), and age categories, and adverse events were mainly gastrointestinal and transient.[1] Other pivotal Asian obesity RCTs have demonstrated comparable results [Table 1]. In STEP-7, semaglutide 2.4 mg achieved –12.1% mean weight loss from baseline (–8.5% placebo-adjusted) in predominantly Chinese adults with obesity.[2] In STEP-6, conducted in Japan and Korea, semaglutide 2.4 mg produced –13.2% weight loss from baseline (–11.1% placebo-adjusted), with 83% achieving ≥5% reduction and a 40% decline in visceral adiposity.[3] In SURMOUNT-CN, tirzepatide 10 mg and 15 mg achieved –12.9% and –15.8% weight loss from baseline (–11.3% and –15.1% placebo-adjusted), with ≥5% response rates of 86%–88%.[4]Table 1: Key obesity randomized controlled trials with glucagon-like peptide-1 receptor agonists in Asian populationsWhen compared with global trials such as STEP-1 (semaglutide 2.4 mg: –14.9% from baseline, –12.4% placebo-adjusted)[5] and SURMOUNT-1 (tirzepatide 15 mg: –20.9% from baseline, –17.8% placebo-adjusted),[6] weight loss outcomes in Asian trials are comparable to those reported in predominantly White populations, possibly reflecting greater visceral adiposity and responsiveness at lower BMI thresholds. Beyond weight loss, CV benefits are critical. In a meta-analysis of eight CV outcome trials, Lee et al.[7] reported that GLP-1RAs reduced MACE by 31% in Asians ((hazard ratio [HR] = 0.69, 95% confidence interval [CI] = 0.58–0.83) compared with 15% in Whites (HR = 0.85, 95% CI = 0.79–0.91; Pinteraction = 0.045), with absolute benefit nearly doubled (absolute risk reduction [ARR] = 2.9%; number needed to treat [NNT] = 35 vs. ARR = 1.4%; NNT = 73). However, the regional distribution of evidence is imbalanced. Most obesity RCTs have been conducted in East Asia. In contrast, South Asia, including India, Pakistan, Bangladesh, and Nepal, lacks large obesity-focused RCTs, despite being home to 1.9 billion people and projected to contribute substantially to the global obesity burden by 2030.[8] Distinctive features of South Asian obesity include the “thin-fat phenotype,” earlier onset of obesity, and visceral adiposity at lower BMI.[8] The SLIMMER trial, together with STEP-6, STEP-7, and SURMOUNT-CN, supports the efficacy of GLP-1RAs in Asian populations. Importantly, both SLIMMER and SURMOUNT-CN enrolled participants at lower BMI thresholds (≥28 or ≥24 with ≥1 comorbidity) than other obesity RCTs, yet achieved comparable efficacy, underscoring the relevance of GLP-1RAs in populations where obesity is defined at lower cutoffs. Dedicated studies in South Asia are required to establish efficacy and safety in this region, and to assess whether lower doses may provide outcomes comparable to maximal dosing, given differences in body composition, adiposity patterns, and drug responsiveness. Biased GLP-1 receptor agonists such as ecnoglutide represent an innovative therapeutic design, though their potential to confer clinical advantages over balanced GLP-1 analogues is yet to be established. Head-to-head studies against pharmacokinetically matched comparators will be required to define their clinical relevance. Nevertheless, ecnoglutide represents a promising addition to the GLP-1RA class and may help improve access to effective obesity treatments worldwide. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.
Source: Journal of Diabetology
Author: Ahmad Alam
Institution: Aligarh Muslim University
Language: English
Subfield: Pharmacology
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
OpenAlex ID: W7118002582