Disease duration as an indicator of the efficacy of liraglutide in patients with type 2 diabetes mellitus

Wilbrink, Francis J; Mudde, Aart N.; Mulder, A. H.; Bhansing, Kavish J.

doi:10.1111/jdi.12857

Cited by 4 publications

(4 citation statements)

References 1 publication

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“…These findings suggest that in patients with relatively long duration of diabetes, GLP-1 RAs could be an effective treatment option. However, previously it was reported that in patients treated with liraglutide uncontrolled on insulins, the glucose-lowering effect depends on the duration of diabetes and beta-cell function [ 16 , 17 ]. In our study, the glucose-lowering effect did not vary based on duration of diabetes, which could be due to differences in study design and patient population.…”

Section: Discussionmentioning

confidence: 99%

Efficacy and Safety of Once Weekly Dulaglutide in East Asian Patients with Type 2 Diabetes: Subgroup Analysis by Potential Influential Factors

Ma¹,

Zhang

Hou

et al. 2020

Diabetes Ther

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Introduction: This subgroup analysis assessed the efficacy and safety of once weekly dulaglutide 1.5 mg and 0.75 mg in East Asian patients with type 2 diabetes (T2D) stratified by key demographic and baseline characteristics. Methods: Change from baseline in glycated hemoglobin (HbA1c), fasting blood glucose (FBG) and body weight were analyzed by age (\ 60 years, C 60 years), gender (male, female), body weight (\ 70 kg, C 70 kg), BMI (\ 25 kg/ m 2 , C 25 kg/m 2), duration of diabetes (\ 10 years, C 10 years), baseline HbA1c (\ 8.5%, C 8.5%) and concomitant oral antihyperglycemic medications (OAMs; metformin only, SU only, metformin ? SU) at week 26 and 52 in East Asian patients from the AWARD-CHN2 study. Incidence of gastrointestinal adverse events (GI AEs) and hypoglycemia was evaluated. Results: A total of 422 East Asian patients with T2D were included in this subgroup analysis. At week 26, the reduction of HbA1c and FBG from baseline were similar across subgroups, except that patients with baseline HbA1c C 8.5% had greater HbA1c and FBG reductions than patients with baseline HbA1c \ 8.5%. Gender analysis showed HbA1c difference that was not clinically significant. The decrease in body weight varied across different subgroups in both dulaglutide doses; however, the difference was not clinically significant. The incidence of GI AEs and total hypoglycemia was generally similar across subgroups in both doses. A similar trend was observed at week 52 in both dulaglutide doses. Conclusions: In East Asian patients with T2D, treatment with dulaglutide (1.5 mg and 0.75 mg) demonstrated significant improvements in glycemic control irrespective of all subgroups, except baseline HbA1c, with greater HbA1c and FBG reductions in patients with higher baseline HbA1c. Dulaglutide was well tolerated with a similar safety profile to other GLP-1 receptor agonists. Trial Registration: ClinicalTrials.gov Identifier: NCT01648582.

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Section: Discussionmentioning

confidence: 99%

Efficacy and Safety of Once Weekly Dulaglutide in East Asian Patients with Type 2 Diabetes: Subgroup Analysis by Potential Influential Factors

Ma¹,

Zhang

Hou

et al. 2020

Diabetes Ther

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“…This finding may suggest an added value of weight loss on glucose reduction in patients with T2D and overweight or obesity. In this study, a significantly greater reduction in HbA1c and SMBG profile was observed in younger patients receiving tirzepatide 15 mg. Interestingly, a previous study in patients with uncontrolled T2D on insulin showed that the glucose-lowering effect of liraglutide was dependent on beta cell function [ 19 , 20 ]. However, we observed that blood glucose control, including reductions in HbA1c, FSG and SMBG profiles, was similar across the three tirzepatide treatment groups by duration of T2D (< 10 vs. ≥ 10 years), which is consistent with the results of a previous subgroup analysis from the global phase 3 SURPASS studies that investigated the glycemic effect of tirzepatide by duration of diabetes [ 21 ].…”

Section: Discussionmentioning

confidence: 99%

Efficacy and Safety of Tirzepatide in Patients with Type 2 Diabetes: Analysis of SURPASS-AP-Combo by Different Subgroups

Bi,

Lu,

Tang

et al. 2024

Diabetes Ther

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Introduction Tirzepatide is a novel glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist. In the SURPASS-AP-Combo trial, once-weekly tirzepatide was associated with improved glycemic control and weight loss versus insulin glargine and was generally well tolerated in an Asia-Pacific, predominately Chinese, population with type 2 diabetes (T2D). This post hoc subgroup analysis of SURPASS-AP-Combo assessed the potential influence of patient baseline characteristics on the efficacy and safety of tirzepatide. Methods Changes from baseline to week 40 in HbA1c, body weight, fasting serum glucose (FSG), and daily glucose average from self-measured blood glucose profiles were analyzed by potential influential factors including age (< 65, ≥ 65 years), sex, baseline HbA1c (≤ 8.5, > 8.5%), body mass index (BMI) (< 25, ≥ 25 kg/m 2 ), body weight (< 75, ≥ 75 kg), duration of diabetes (< 10, ≥ 10 years), and concomitant oral antihyperglycemic medications (metformin, metformin plus sulphonylurea). Gastrointestinal adverse events and hypoglycemia were also evaluated. Results At week 40, all tirzepatide doses were associated with reduced HbA1c, body weight, FSG, and daily glucose average from baseline in all subgroups. Greater HbA1c reductions were achieved in patients with higher baseline HbA1c across all tirzepatide doses, higher body weight with 10 mg and younger age with 15 mg tirzepatide. Greater reductions in body weight were observed in patients with higher body weight across all tirzepatide doses, lower baseline HbA1c with 5 mg and higher BMI with 5 mg tirzepatide. Conclusions In this post hoc analysis, tirzepatide was associated with reduced blood glucose and body weight in a predominantly Chinese population with T2D across different subgroups, consistent with previous reports for tirzepatide. Clinical Trial Registration NCT04093752. Supplementary Information The online version contains supplementary material available at 10.1007/s13300-024-01561-2.

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“…A possible role of Gal-3 as a predictor of successful therapy in patients with T2DM has been previously discussed [ 44 ]. Since liraglutide seems most effective in patients with the highest remaining β‐cell function [ 45 , 46 ] our hypothesis is that low basal Gal-3 levels may serve as biomarkers to identify this subset of patients. This is supported by a recent experimental model of obesity-induced diabetogenesis, showing that Gal-3 overexpression facilitates β-cell damage, enhances oxidative stress and beta-cell apoptosis [ 47 ].…”

Section: Discussionmentioning

confidence: 99%

Effects of liraglutide vs. lifestyle changes on soluble suppression of tumorigenesis-2 (sST2) and galectin-3 in obese subjects with prediabetes or type 2 diabetes after comparable weight loss

Simeone

Tripaldi

Michelsen

et al. 2022

Cardiovasc Diabetol

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Background Soluble suppression of tumorigenesis-2 (sST2) and galectin (Gal)-3 are two biomarkers related to inflammation, metabolic disturbances and to myocardial fibrosis that characterize several cardiac pathological conditions. Increased circulating levels of these molecules have been associated with risk of cardiovascular death. Treatment with liraglutide, a glucagon-like peptide 1 analog, is associated with weight loss, improved glycemic control, and reduced cardiovascular risk. We wanted to assess (I) potential differences between subjects with prediabetes or type 2 diabetes mellitus (T2DM) and healthy controls in sST2 and Gal-3 circulating levels, and their relationship with glycemic control and markers of beta cell function and myocardial injury; (II) whether liraglutide treatment modulates these markers in subjects with prediabetes or early T2DM independently of weight loss; (III) whether baseline levels of any of these two molecules may predict the response to liraglutide treatment. Methods Forty metformin-treated obese subjects (BMI ≥ 30) with prediabetes [impaired fasting glucose (IFG) or impaired glucose tolerance (IGT) or both (n = 23)] or newly diagnosed T2DM (n = 17), were randomized to liraglutide or lifestyle counseling until achieving a comparable weight loss (7% of initial body weight). Thirteen subjects were enrolled as healthy controls for baseline sST2 and Gal-3 levels. Results Baseline sST2 levels were comparable between controls and obese patients (p = 0.79) whereas Gal-3 levels were significantly higher in patients as compared to controls (p < 0.001). Liraglutide treatment, but not weight loss achieved by lifestyle counseling, decreased plasma sST2 levels (− 9%, beta = − 14.9, standard deviation 6.9, p = 0.037) while Gal-3 levels did not change. A reduction in serum hs-Troponin I was observed after intervention, due to a 19% (p = 0.29) increase in the lifestyle arm, and a 25% decrease (p = 0.033) in the liraglutide arm (between-group difference p = 0.083). Lower baseline Gal-3 levels predicted a better improvement in beta cell function after liraglutide treatment. Conclusions Liraglutide-induced reduction in sST2 and possibly hs-TnI suggests that in obese patients with prediabetes or early T2DM this drug may have a positive effect on (cardiac) fibrosis, whereas plasma level of Gal-3 before liraglutide initiation may predict response to the drug in terms of beta cell function improvement. Trial registration Eudract: 2013-001356-36

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Disease duration as an indicator of the efficacy of liraglutide in patients with type 2 diabetes mellitus

Cited by 4 publications

References 1 publication

Efficacy and Safety of Once Weekly Dulaglutide in East Asian Patients with Type 2 Diabetes: Subgroup Analysis by Potential Influential Factors

Efficacy and Safety of Once Weekly Dulaglutide in East Asian Patients with Type 2 Diabetes: Subgroup Analysis by Potential Influential Factors

Efficacy and Safety of Tirzepatide in Patients with Type 2 Diabetes: Analysis of SURPASS-AP-Combo by Different Subgroups

Effects of liraglutide vs. lifestyle changes on soluble suppression of tumorigenesis-2 (sST2) and galectin-3 in obese subjects with prediabetes or type 2 diabetes after comparable weight loss

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