GRAPHICAL ABSTRACT

Highlights

• Dulaglutide improved glycemic control over 24 weeks, independent of BMI or fat.

• Decreased leptin and increased obestatin were independently linked to HbA1c reduction.

• These hormonal shifts may explain individual differences in GLP-1 RA response.

INTRODUCTION

Glucagon-like peptide-1 (GLP-1) is an incretin hormone released from enteroendocrine cells in response to food intake, which enhances glucose-dependent insulin secretion [1,2]. GLP-1 receptor agonists (GLP-1 RAs) have emerged as a cornerstone in the management of type 2 diabetes mellitus (T2DM) and obesity, offering significant glycemic control, weight reduction, and cardiovascular benefits [3,4]. These agents enhance insulin secretion, suppress glucagon release, and slow gastric emptying, thereby improving both postprandial and fasting glucose levels [5,6].

Although the classical mechanisms of GLP-1 RAs are well established, growing evidence suggests that their metabolic benefits may also be mediated through the modulation of adipokines such as leptin and adiponectin [7-9]. Adipokines, bioactive molecules secreted by adipose tissue, play pivotal roles in glucose metabolism, insulin sensitivity, and systemic inflammation [10]. Additionally, GLP-1 has been shown to influence the secretion of gut hormones, including peptide YY and ghrelin, and affect adipokine profiles [11-13]. However, whether these alterations in adipokines and gut hormones are directly involved in the glycemic benefits of GLP-1 RAs remains unclear.

According to the 2024 American Diabetes Association (ADA) guidelines, GLP-1 RAs are recommended as part of a glucose-lowering regimen regardless of glycosylated hemoglobin (HbA1c) levels in patients with T2DM at a high atherosclerotic cardiovascular risk [14]. Regarding glycemic control, individuals with poorly controlled hyperglycemia associated with T2DM can be effectively treated with GLP-1 RAs [14]. However, few studies have evaluated the predictors of glycemic response to GLP-1 RA treatment in patients with T2DM. Although GLP-1 RAs are known to be effective in patients with overweight or obesity due to their weight-loss properties, it remains unclear whether their glycemic control effects are proportional to the extent of weight loss or appetite suppression induced by GLP-1 RAs. Furthermore, it has not been determined which individuals should be prioritized for GLP-1 RA therapy for glycemic control among patients without obesity, who constitute a substantial proportion of the T2DM population in Asia [15].

Therefore, this study aimed to investigate changes in abdominal fat, food cravings, and circulating levels of adipokines and gut hormones following dulaglutide treatment in patients with T2DM and to determine which of these changes were related to the glucose-lowering effects of dulaglutide.

METHODS

Study participants

Between June 2019 and December 2022, 82 patients were recruited from the endocrinology outpatient clinic at Korea University Ansan Hospital. We enrolled patients aged 20 to 70 years with T2DM who had HbA1c levels ≥7% despite ongoing treatment with one of the following antidiabetic regimens: (1) metformin and sulfonylurea; (2) basal insulin with or without metformin; (3) basal insulin, metformin, and another oral hypoglycemic agent (OHA); (4) metformin, sulfonylurea, and another OHA; or (5) basal insulin, rapid-acting insulin, and metformin.

Participants were excluded if they had type 1 diabetes mellitus, a history of pancreatitis, or advanced renal or hepatic failure. Additional exclusion criteria included a personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2, active psychiatric disorders, current malignancies, rheumatic systemic diseases, systemic infections, or chronic obstructive pulmonary disease. Individuals who had received systemic corticosteroids, immunosuppressive agents, anti-obesity medications (oral or injectable), or GLP-1 RAs within the previous 6 months were also excluded. Furthermore, participants who were pregnant, planning to become pregnant during the study period, or had a body mass index (BMI) <18.5 kg/m² were not eligible for inclusion.

Study design and procedures

This single-center, prospective, observational study was designed to evaluate changes in visceral and subcutaneous fat, food cravings, and circulating levels of adipokines and gastrointestinal hormones following treatment with dulaglutide. Following baseline assessments after enrollment, participants initiated dulaglutide treatment at a dose of 0.75 mg once weekly. Dulaglutide was either added to the existing antidiabetic regimens (1 and 2) or substituted for one OHA or rapid-acting insulin in the other regimens. The treatment was continued for 24 weeks.

The participants attended three study visits: at baseline (week 0, visit 1 [V1]), week 12 (visit 2 [V2]), and week 24 (visit 3 [V3]). At each visit, a comprehensive physical examination and anthropometric measurements were performed. At V1 and V3, blood and urine samples were collected after a 12-hour overnight fast to assess adipokine and gastrointestinal hormone levels. Participants also completed the General Food Cravings Questionnaire (FCQ)-Trait and underwent non-contrast abdominal computed tomography (CT) scans at these two time points. At V2, only routine blood tests (excluding adipokines and gastrointestinal hormones) and anthropometric measurements were performed.

Demographic, anthropometric, and laboratory measurements

Smoking status and alcohol consumption were categorized as never, former, or current. Regular exercise was defined as physical activity performed three to four times per week for at least 30 minutes per session during the previous month. Trained nurses obtained anthropometric measurements, including height, weight, and waist circumference. Trained nurses measured blood pressure using standard methods.

BMI was calculated as weight in kilograms divided by the square of height in meters. Fasting plasma glucose (FPG), HbA1c, serum total cholesterol, triglycerides, high-density lipoprotein (HDL) cholesterol, and low-density lipoprotein (LDL) cholesterol levels were measured after a 12-hour overnight fast using an autoanalyzer (ADVIA 1650, Siemens, Tarrytown, NY, USA). Serum insulin levels were measured using an immunoradiometric assay kit (INS-IRMA Kit, BioSource, Nivelles, Belgium) with a Packard γ counter system. Insulin resistance was estimated using the homeostasis model assessment of insulin resistance index (HOMA-IR) using the following formula: HOMA-IR=(fasting insulin [μU/mL]×FPG [mg/dL])/405 [16]. HOMA of β-cell function (HOMA-β) was calculated using the following formula: HOMA-β=360×fasting insulin (μU/mL)/(FPG [mg/dL]–63) [16].

Measurement of visceral and subcutaneous fat

The abdominal adipose tissue area was assessed using non-contrast abdominal CT scans at V1 and V3. Visceral and subcutaneous fat were measured at the level of the L4–L5 vertebrae using a 128-slice CT scanner (Ingenuity Core 128, Philips Healthcare, Cleveland, OH, USA), and the images were converted into a format compatible with commercial software (Extended Brilliance Workspace, Philips Healthcare, Cleveland, OH, USA). Visceral and subcutaneous fat areas were quantified based on attenuation thresholds ranging from –190 to –30 Hounsfield units.

Food craving questionnaires

General tendencies toward food cravings were assessed at baseline (V1) and week 24 (V3) using the General FCQ-Trait [17]. This standardized, self-administered questionnaire comprises 21 items evaluating an individual’s habitual inclination toward food cravings across four subscales: (1) preoccupation with food (six items); (2) loss of control over eating (six items); (3) positive outcome expectancy (five items); and (4) emotional craving (four items). Responses were rated on a six-point Likert scale ranging from 1 (never/not applicable) to 6 (always), with higher scores indicating greater tendencies toward food cravings. The total General FCQ-Trait score was calculated as the sum of the four subscale scores. The Korean version of the General FCQ-Trait, validated with good reliability in prior studies [18], was used in this study.

Measurement of adipokines and gastrointestinal hormones

Circulating levels of adipokines and gastrointestinal hormones were measured using enzyme-linked immunosorbent assay (ELISA) kits, according to the manufacturer’s protocols. Obestatin levels were measured using the Human Obestatin EIA kit (RayBiotech, Peachtree Corners, GA, USA; Cat No. EIA-OBS-1). Leptin was assessed using the Human Leptin ProQuantum Immunoassay Kit (Invitrogen, Thermo Fisher Scientific, Waltham, MA, USA; Cat No. A45250). Adiponectin was measured using the Human Adiponectin ProQuantum Immunoassay Kit (Invitrogen, Thermo Fisher Scientific; Cat No. A44838). Ghrelin levels were determined using the Ghrelin Human ELISA kit (Invitrogen, Thermo Fisher Scientific; Cat No. BMS2192). Resistin was quantified using the Resistin Human ELISA Kit (Invitrogen, Thermo Fisher Scientific; Cat No. BMS2040).

Statistical analysis

The sample size was calculated based on the results of a previous study [19] using G*power version 3.1.6 (Heinrich Heine University, Düsseldorf, Germany) with an effect size of 0.355 (β=0.20, α=0.05). Assuming a dropout rate of 20%, the calculated sample size was increased from 65 to 82 participants to ensure sufficient power. Baseline characteristics are presented as number (%), mean±standard deviation, or median with interquartile range (IQR), as appropriate. Changes in metabolic parameters, adipokine concentrations, and gastrointestinal hormone levels after 12 and 24 weeks of dulaglutide treatment were analyzed using either paired t-tests or Wilcoxon signed-rank tests, depending on the normality of distribution for each variable. Changes in subscale scores on the General FCQ-Trait from baseline to week 24 were assessed using the Wilcoxon signed-rank test. The internal consistency of the General FCQ-Trait was evaluated using Cronbach’s α coefficient.

Spearman’s correlation analysis was used to explore the associations between the total General FCQ-Trait score at baseline (V1) and various metabolic parameters. Partial Spearman’s correlation, adjusted for age, sex, and BMI, was conducted to assess the relationship between baseline FCQ scores and leptin levels. Participants were classified as glycemic responders if their HbA1c decreased by ≥0.5% and/or reached <7.0% from baseline to week 24, and as non-responders if their HbA1c decreased by <0.5% and remained ≥7.0% at week 24. Differences in baseline characteristics between glycemic responders and non-responders were analyzed using the Student’s t-test, Wilcoxon rank-sum test, or chi-square test, depending on the distribution and nature of the variables.

Multivariable linear regression analysis was performed to investigate the association between hormonal changes and the change in HbA1c from baseline to week 24 (ΔHbA1c [V3–V1]). The model was adjusted for potential confounders, including age, sex, smoking status, alcohol consumption, physical activity, diabetes duration, BMI, use of anti-hypertensive and lipid-lowering medications, basal insulin use, antidiabetic agents replaced by dulaglutide, and baseline HbA1c levels. All P values were two-tailed, with values <0.05 considered statistically significant. Statistical analyses were conducted using SAS software version 9.4 (SAS Institute Inc., Cary, NC, USA).

Ethics statement

This study was conducted in accordance with the principles of the Declaration of Helsinki of the World Medical Association and was approved by the Institutional Review Board (IRB) of Korea University Ansan Hospital (IRB No. 2019AS0002). All participants provided written informed consent. The study was registered at https://cris.nih.go.kr in accordance with the World Health Organization International Clinical Trials Registry Platform.

RESULTS

Baseline characteristics

Of the 91 patients who were screened, 82 were enrolled in the study, and 67 completed the final visit at week 24 (Supplementary Fig. 1). The baseline demographic and clinical characteristics of the participants are summarized in Table 1. The mean age was 52.0±9.6 years, and 49.3% of the participants were male. The median BMI and duration of diabetes were 27.8 kg/m² and 10 years, respectively. Additionally, the mean HbA1c level was 8.7%±1.1%. The most frequently discontinued hypoglycemic agents upon initiation of dulaglutide were dipeptidyl peptidase IV inhibitors (53.7%), followed by sulfonylureas (19.4%), and sodium-glucose cotransporter-2 (SGLT2) inhibitors (17.9%). The most common antidiabetic regimen maintained in combination with dulaglutide was metformin and sulfonylurea (59.7%), followed by basal insulin with or without metformin (40.3%). There was no significant change in the metformin dose between baseline and week 24 (1,820.9±492.0 mg at baseline vs. 1,798.5±506.1 mg at week 24, P=0.358).

Changes in metabolic variables after 12- and 24-week dulaglutide treatment

The median HbA1c reduction from baseline was –0.7% (IQR, –1.6 to –0.1) at week 12 and –0.7% (IQR, –1.3 to 0.2) at week 24 after dulaglutide treatment; both changes were statistically significant (P<0.001) (Table 2). Waist circumference, FPG, total cholesterol, and both HDL and LDL cholesterol levels also significantly decreased at week 12. At week 24, median HOMA-β increased by 10.4 (IQR, –3.6 to 37.3; P=0.005), and median waist circumference decreased by 1.0 cm (IQR, –3.0 to 0.5; P=0.001). No significant changes were observed in blood pressure, BMI, triglyceride, HOMA-IR, albumin-to-creatinine ratio, or visceral and subcutaneous fat mass over 24 weeks.

Changes in food craving and adipokine levels after dulaglutide treatment

In patients with T2DM, the total General FCQ-Trait score significantly decreased at 24 weeks after dulaglutide treatment (P=0.009) (Table 3). Among the subscales of the questionnaire, the scores for preoccupation with food (P=0.02), loss of control (P=0.024), and positive outcome expectancy (P<0.001) were significantly reduced, whereas emotional craving remained unchanged. The total General FCQ-Trait score at baseline was positively correlated with BMI, total cholesterol, and LDL cholesterol levels (Supplementary Table 1).

Regarding adipokine changes (Fig. 1), fasting levels of leptin (P<0.001) and adiponectin (P=0.002) decreased after 24 weeks of dulaglutide treatment. In contrast, obestatin levels increased, although this change was not statistically significant. Ghrelin and resistin levels also showed no significant changes during the study period. At baseline, leptin levels were positively correlated with the total General FCQ-Trait score (Supplementary Table 1); however, this association was no longer statistically significant after adjusting for BMI (data not shown).

Clinical and hormonal characteristics of glycemic responders vs. non-responders

At week 24, HbA1c levels significantly decreased from 8.9%±0.2% to 7.4%±0.18% in 39 of 67 patients (58.2%) with T2DM (P<0.001), whereas in the remaining 28 patients, HbA1c significantly increased from 8.3%±0.13% to 8.9%±0.25% despite dulaglutide treatment (P=0.002) (Fig. 2A). Compared to glycemic responders, non-responders had higher baseline BMI and waist circumference and lower baseline HbA1c levels (Supplementary Table 2), while no significant differences were observed in age, sex, lifestyle factors, or baseline food cravings. After 24 weeks, glycemic responders showed significant reductions in General FCQ-Trait scores and increases in HOMA-β values (Fig. 2B and C). Although BMI remained unchanged in both groups, waist circumference decreased significantly in responders but increased in non-responders (Fig. 2D and E). At week 24, leptin levels were significantly reduced only in responders, whereas adiponectin levels decreased significantly only in non-responders (Fig. 2F and G). Obestatin levels increased exclusively in the responder group, although the change did not reach statistical significance (P=0.063) (Fig. 2H).

Hormonal changes associated with glycemic response to dulaglutide treatment

Multivariable linear regression analyses were performed to evaluate the association between changes in adipokines, gut hormones, and glycemic improvement following dulaglutide treatment (Table 4). A greater reduction in leptin levels (standardized β=0.536, P<0.001) and a greater increase in obestatin levels (β=–0.387, P=0.002) were independently associated with HbA1c reduction. Furthermore, higher baseline levels of leptin and obestatin were associated with greater HbA1c improvement (both P<0.001, data not shown). In contrast, a decrease in adiponectin levels was significantly associated with an increase in HbA1c (β=–0.401, P=0.005). However, neither baseline values nor changes in BMI, total General FCQ-Trait score, or abdominal fat mass were significantly associated with the glycemic response to dulaglutide over 24 weeks (data not shown).

DISCUSSION

In this prospective observational study, we investigated the metabolic, hormonal, and behavioral factors associated with the glycemic response to once-weekly low-dose dulaglutide in patients with T2DM. Over 24 weeks, dulaglutide significantly improved glycemic control, with over half of participants achieving clinically meaningful reduction in HbA1c. Treatment also enhanced β-cell function and reduced food cravings, despite no significant changes in BMI or visceral fat. Notably, decreases in leptin and increases in obestatin were independently associated with glycemic improvement, whereas decreases in adiponectin were linked to worsening outcomes. These findings suggest weight-independent mechanisms that may underlie the heterogeneous glycemic responses to GLP-1 RA therapy.

According to the joint recommendations of the ADA and the European Association for the Study of Diabetes [20,21], GLP-1 RAs are prescribed following inadequate glycemic control with metformin, in combination with two or more oral antidiabetic agents, or as an add-on to basal insulin for treatment intensification. Despite their well-established efficacy, clinical responses to GLP-1 RA therapy vary considerably among individuals. A recent meta-analysis suggested that factors such as age, sex, ethnicity, BMI, and baseline HbA1c levels may influence the glycemic response to GLP-1 RAs in patients with T2DM [22]. However, in our study, we found no association between age, sex, or BMI and changes in HbA1c levels following dulaglutide treatment. Additionally, contrary to our expectations, baseline food cravings, visceral fat mass, and insulin resistance were not related to the glycemic response. These findings suggest that traditional demographic and metabolic characteristics may not reliably predict glycemic outcomes with GLP-1 RA therapy.

Our study provides valuable insights into the relationship between glycemic improvement and changes in adipokines and appetite-related hormones following GLP-1 RA treatment. We found that reductions in HbA1c levels after dulaglutide treatment were independently associated with alterations in circulating leptin and adiponectin, which are key hormones involved in insulin sensitivity and metabolic regulation [23-25]. To date, limited evidence is available on the correlation between GLP-1 RA-induced glycemic changes and adipokine dynamics. Several studies have examined the modulation of adipokines by GLP-1 RAs in patients with T2DM. A meta-analysis of 13 randomized controlled trials reported significant reductions in leptin levels with GLP-1 RA therapy [7]. Moreover, recent clinical data suggest that GLP-1 RAs may enhance leptin sensitivity by increasing leptin receptor expression [8], supporting the hypothesis that GLP-1 RA treatment may help overcome leptin resistance, a common pathophysiological feature in T2DM.

However, our findings regarding adiponectin differ from those of previous reports showing increased or unchanged levels after GLP-1 RA treatment [9]. In our study, adiponectin levels decreased after dulaglutide treatment, whereas resistin levels remained largely unchanged. These discrepancies may stem from differences in the study populations, including racial and ethnic backgrounds, as well as variations in the specific GLP-1 RA used, treatment duration, and concurrent medications. Further research is warranted to clarify the clinical relevance of adipokine responses to GLP-1 RA therapy and to determine whether these hormonal changes mediate differential glycemic outcomes across diverse patient populations.

In this study, we measured obestatin, a gut-derived peptide that has not been well characterized in the context of GLP-1 RA therapy. Ghrelin and obestatin are derived from the same preprohormone but exert opposite effects; ghrelin stimulates appetite, while obestatin suppresses it [26]. In addition to its anorexigenic properties, obestatin has shown beneficial effects in various organ systems. Experimental studies have suggested that obestatin promotes pancreatic β-cell proliferation, inhibits β-cell apoptosis, and may enhance insulin secretion and the regeneration of β-cells [27,28]. Although the specific receptor for obestatin remains unclear, GLP-1 receptor signaling has been proposed to mediate some of its biological effects [28].

Previous studies have reported lower obestatin levels in individuals with obesity and T2DM [29,30]. However, to the best of our knowledge, no prior study has evaluated the changes in obestatin levels before and after GLP-1 RA treatment. Our study is the first to demonstrate that a greater increase in fasting obestatin levels is significantly associated with a larger reduction in HbA1c levels after 24 weeks of dulaglutide therapy. This observation is consistent with experimental evidence suggesting that obestatin upregulates GLP-1R expression and enhances β-cell survival and insulin secretion through GLP-1 receptor-dependent mechanisms [28]. Given that higher baseline obestatin levels were also associated with a more favorable glycemic response to dulaglutide treatment (data not shown), this finding warrants further investigation into its potential as a predictive biomarker.

In addition, we observed that once-weekly low-dose dulaglutide (0.75 mg/week) improved β-cell function without significant changes in BMI. Although the weight-reducing effects of GLP-1 RAs may be less pronounced in Asians than in other ethnic groups [31,32], their glucose-lowering efficacy appears greater in Asians, likely due to the predominant role of β-cell dysfunction rather than insulin resistance in the pathophysiology of T2DM [33,34]. Our findings therefore suggest that low-dose dulaglutide may be an effective therapeutic option for glycemic control in non-obese Asian patients with T2DM.

In our subgroup analysis, patients who discontinued SGLT2 inhibitors and switched to dulaglutide had a lower proportion of glycemic responders than those who discontinued other OHAs (33% vs. 65%, P=0.056; data not shown). This finding suggests that prior exposure to SGLT2 inhibitors may attenuate the therapeutic efficacy of subsequent GLP-1 RA treatment, potentially due both to the loss of complementary glucose-, weight-, and adipokine-modulating effects of SGLT2 inhibition [35] and to a greater metabolic burden in this subgroup, such as obesity, insulin resistance or cardiorenal complications. However, given the limited sample size in each subgroup, these results should be interpreted with caution and confirmed in larger studies.

This study had several limitations. First, its single-center design and relatively small sample size may have limited the generalizability of our findings. Second, the observational nature of the study precludes causal inference regarding the associations between adipokine changes and glycemic response. Third, dulaglutide was administered at a relatively low dose of 0.75 mg once weekly, which is commonly used in Asian populations but lower than the standard 1.5 mg dose used in broader clinical practice. Therefore, the observed metabolic and hormonal changes may not fully reflect the effects of higher doses of dulaglutide. Fourth, prior drug discontinuation or other unmeasured factors may have affected adipokine and hormone levels, influencing the observed associations with glycemic outcomes. Finally, the study population primarily consisted of Korean patients, which may limit its applicability to other ethnic groups with different adipokine profiles or treatment responses.

Despite these limitations, our study is the first to comprehensively evaluate adipokines and gastrointestinal hormones related to appetite and energy balance before and after dulaglutide treatment. Notably, we included hormones such as obestatin and resistin, which have not been extensively evaluated in previous studies on GLP-1 RAs, thereby providing novel insights. Another key strength is the simultaneous assessment of food craving using the General FCQ-Trait and serum adipokine levels, enabling the integrated analysis of food craving and hormonal changes in relation to insulin resistance and glycemic markers. We found that patients with significant HbA1c improvement exhibited greater hormonal changes over 24 weeks, including increased obestatin and decreased leptin levels. These findings offer new perspectives on the characteristics of glycemic responders to dulaglutide, particularly in the Asian population, and suggest the potential utility of specific hormone markers, especially obestatin and leptin, as predictors of therapeutic response to GLP-1 RAs.

In summary, our study demonstrated that dulaglutide improves glycemic control in patients with T2DM, independent of changes in BMI or abdominal fat. Hormonal changes were significantly associated with glycemic response, with reduced leptin and increased obestatin levels linked to improvements and decreased adiponectin levels associated with worse outcomes. These findings suggest that specific adipokines and gut hormones may contribute to the therapeutic effects of GLP-1 RAs and could offer insights into individual variability in treatment response. Further large-scale, multi-ethnic studies are warranted to confirm these associations and evaluate their potential relevance in personalized diabetes management.

SUPPLEMENTARY MATERIALS

NOTES

CONFLICTS OF INTEREST

No potential conflict of interest relevant to this article was reported.

AUTHOR CONTRIBUTIONS

Conception or design: I.J., J.H.Y.

Acquisition, analysis, or interpretation of data: all authors.

Drafting the work or revising: I.J., J.H.Y.

Final approval of the manuscript: J.H.Y.

FUNDING

This work was supported by a grant (Ji Hee Yu, 2018F-6) from the Korean Diabetes Association and the National Research Foundation of Korea (NRF) grants funded by the Korea government (MSIT) (2020R1F1A1074265, RS-2025-00562220), and a Korea University Ansan Hospital grant (O2515231 to Inha Jung).

ACKNOWLEDGMENTS

Generative artificial intelligence (ChatGPT, OpenAI) was used for grammar editing purposes. All content was reviewed and approved by the authors, who take full responsibility for its integrity and accuracy.

DATA AVAILABILITY

The datasets generated and/or analyzed in the current study are not publicly available because of Institutional Review Board (IRB) restrictions. Access to the data was strictly limited to individuals explicitly approved by the IRB for this specific research purpose. Any request for data sharing by external parties requires the submission of a formal proposal and subsequent approval by the relevant IRB or institutional authority.

Fig. 1.

Changes in adipokine and gut hormone levels after 24 weeks of dulaglutide treatment. Values are presented as mean±standard error (SE). (A) Leptin, (B) adiponectin, (C) obestatin, (D) ghrelin, and (E) resistin. Statistical significance is indicated as follows: ^aP<0.01, ^bP<0.001 vs. baseline (week 0).

Fig. 2.

Metabolic, food craving, and adipokine changes in glycemic responders vs. non-responders to dulaglutide. Glycemic responders are shown as black circles with solid lines and non-responders as white circles with dashed lines. Values are presented as mean±standard error. (A) Glycosylated hemoglobin (HbA1c), (B) General Food Cravings Questionnaire (FCQ)-Trait score, (C) homeostatic model assessment of β-cell function (HOMA-β), (D) waist circumference, (E) body mass index (BMI), (F) leptin, (G) adiponectin, and (H) obestatin. Statistical significance is indicated as follows: ^aP<0.05, ^bP<0.01, ^cP<0.001 vs. baseline (week 0).

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Jung I, Choi H, Choi IY, Cho HJ, Park SY, Lee DY, Seo JA, Kim NH, Yu JH. Glycemic Improvement with Low-Dose Dulaglutide Is Associated with Leptin and Obestatin Modulation in Type 2 Diabetes Mellitus. Diabetes Metab J. 2025 Nov 24. doi: 10.4093/dmj.2025.0681. Epub ahead of print.

Received: Jul 28, 2025; Accepted: Sep 23, 2025

DOI: https://doi.org/10.4093/dmj.2025.0681.

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