Dataset Information

Change in pharmacodynamic variables following once-weekly tirzepatide treatment versus dulaglutide in Japanese patients with type 2 diabetes (SURPASS J-mono substudy).

ABSTRACT:

Aim

To evaluate the pharmacodynamic effects of tirzepatide, a novel dual glucagon-like peptide-1 receptor and glucose-dependent insulinotropic polypeptide receptor agonist, compared with dulaglutide in patients with type 2 diabetes.

Materials and methods

SURPASS J-mono was a 52-week, multicentre, randomized, double-blind, parallel, active-controlled, Phase 3 study, conducted in Japan. This substudy of SURPASS J-mono evaluated postprandial metabolic variables and appetite after a meal tolerance test, and body composition measured by bioelectrical impedance analysis.

Results

Of 636 participants in SURPASS J-mono, 48 were included in this substudy and assigned to tirzepatide 5 mg (n = 9), tirzepatide 10 mg (n = 11), tirzepatide 15 mg (n = 9), or dulaglutide 0.75 mg (n = 19). Participants had a mean (standard deviation) age of 58.6 (7.5) years, duration of diabetes of 6.0 (6.3) years, and body mass index of 27.5 (3.5) kg/m² . Mean glycated haemoglobin at baseline was 66 mmol/mol (8.22%). Following a standardized meal test, statistically significant differences in change from baseline in area under the concentration versus time curve from time zero to 6 h after dose for glucose, insulin, glucagon, C-peptide and triglycerides were observed in all tirzepatide treatment arms, except triglycerides at 10 mg, compared with dulaglutide at Week 32. For body composition, tirzepatide 10 mg and 15 mg resulted in a significant reduction in body weight, and all doses of tirzepatide resulted in a significant reduction in body fat mass at Week 52.

Conclusions

Compared with dulaglutide, tirzepatide showed greater potential for normalizing metabolic factors after a standardized meal. Tirzepatide reduced body weight and body fat mass.

SUBMITTER: Yabe D

PROVIDER: S-EPMC10092154 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature

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Publications

Change in pharmacodynamic variables following once-weekly tirzepatide treatment versus dulaglutide in Japanese patients with type 2 diabetes (SURPASS J-mono substudy).

Yabe Daisuke D Kawamori Dan D Seino Yusuke Y Oura Tomonori T Takeuchi Masakazu M

Diabetes, obesity & metabolism 20221102 2

<h4>Aim</h4>To evaluate the pharmacodynamic effects of tirzepatide, a novel dual glucagon-like peptide-1 receptor and glucose-dependent insulinotropic polypeptide receptor agonist, compared with dulaglutide in patients with type 2 diabetes.<h4>Materials and methods</h4>SURPASS J-mono was a 52-week, multicentre, randomized, double-blind, parallel, active-controlled, Phase 3 study, conducted in Japan. This substudy of SURPASS J-mono evaluated postprandial metabolic variables and appetite after a m ...[more]

PMID: 36184780

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Project description:IntroductionThe objective of this work was to assess the association of tirzepatide with changes in insulin sensitivity and beta-cell function in Japanese patients with type 2 diabetes (T2D).MethodsThis was a prespecified analysis of SURPASS J-mono, a multicenter, randomized, double-blind, active-controlled phase 3 study in Japanese participants with T2D. Participants were randomly assigned to receive tirzepatide 5, 10, 15 mg, or dulaglutide 0.75 mg once weekly for 52 weeks. Changes from baseline in homeostatic model assessment (HOMA2) parameters were assessed by a mixed model for repeated measures. Post hoc subgroup analyses were conducted based on high and low baseline C-peptide categories (cutoff: median 1.86 µg/l).ResultsThis analysis included 636 participants (tirzepatide 5 mg: n = 159; 10 mg: n = 158; 15 mg: n = 160; dulaglutide 0.75 mg: n = 159). Fasting insulin and C-peptide levels were significantly reduced from baseline at week 52 at all three tirzepatide doses compared with dulaglutide 0.75 mg (estimated treatment differences [ETDs] for tirzepatide 5, 10, and 15 mg, respectively: insulin, - 22.6%, - 29.8%, and - 31.0%; C-peptide, - 14.2%, - 21.5%, and - 20.7%; p < 0.001 all comparisons). Insulin sensitivity and beta-cell function indices significantly increased in all tirzepatide groups compared with the dulaglutide 0.75-mg group (ETDs for tirzepatide 5, 10, and 15 mg, respectively: HOMA2-%S [insulin], 31.8%, 43.2%, and 49.9%; HOMA2-%S [C-peptide], 24.8%, 33.9%, and 38.2%; HOMA2-%B [insulin], 27.3%, 34.9%, and 40.6%; HOMA2-%B [C-peptide], 31.6%, 40.1%, and 46.7%; p < 0.001 all comparisons). Regardless of baseline C-peptide level, the tirzepatide groups showed significant improvement in glycated hemoglobin at week 52 compared with the dulaglutide group (C-peptide < 1.86 µg/l: - 2.31% to - 2.75% vs. - 1.45%; ≥ 1.86 µg/l: - 2.43% to - 2.89% vs. - 1.12%; p < 0.001).ConclusionsIn these prespecified and post hoc analyses, tirzepatide was associated with improved insulin sensitivity and insulin secretion in Japanese participants with T2D, which may result in reduced fasting insulin levels.ClinicaltrialsGOV: NCT03861052.

Project description:IntroductionThe presence of metabolic abnormalities in patients with type 2 diabetes (T2D) increases the risk of cardiovascular disease and other comorbidities. This analysis compared the effects of tirzepatide (5, 10, and 15 mg) and dulaglutide 0.75 mg on the prevalence of metabolic abnormalities in Japanese patients with T2D.MethodsThis was a post hoc analysis of SURPASS J-mono, a multicenter, randomized, double-blind, active-controlled, parallel-group, phase 3 trial that compared the efficacy and safety of tirzepatide monotherapy (5, 10, and 15 mg) to dulaglutide 0.75 mg in Japanese patients with T2D. Thresholds for abnormalities were based on the Japanese criteria for metabolic syndrome. Proportions of participants meeting a composite endpoint (visceral fat accumulation measured by waist circumference plus two or more of dyslipidemia, hypertension, or hyperglycemia) or individual component thresholds were calculated at baseline and week 52 for the overall population and for baseline body mass index (BMI) subgroups (< 25, 25 to < 30, and ≥ 30 kg/m2).ResultsOf 636 randomized participants, 431 (67.8%) met the composite endpoint at baseline, with similar findings observed across treatment arms. At week 52, the proportion of participants on treatment that met the composite endpoint was 31.7%, 23.0%, and 14.2% in the tirzepatide 5-, 10-, and 15-mg arms, respectively, and 56.5% in the dulaglutide arm (p < 0.001). A higher proportion met the composite endpoint at baseline in the BMI 25 to < 30 and ≥ 30 kg/m2 subgroups (73.2-79.3%) compared with the < 25 kg/m2 subgroup (45.3%), with reductions observed across all BMI subgroups treated with tirzepatide. The proportion of participants with individual metabolic abnormalities showed similar trends to those observed for the composite endpoint. Tirzepatide was consistently superior to dulaglutide across all assessments.ConclusionsTirzepatide reduced the prevalence of multiple metabolic abnormalities, indicating tirzepatide may have metabolic benefit in Japanese patients with T2D.Trial registrationClinicalTrials.gov, NCT03861052.

Project description:BackgroundType 2 Diabetes Mellitus (T2DM) is a highly prevalent disease worldwide and in Colombia, representing one of the main causes of death and placing a considerable burden on healthcare systems. 13 classes of drugs are approved for the treatment of T2DM, with Glucagon-like Peptide-1 (GLP-1) receptor agonists being a first-line treatment option for patients with or at high risk of certain cardiovascular diseases and chronic kidney disease. The objective of this study is to conduct a short-term cost-effectiveness analysis of once-weekly semaglutide versus once-weekly dulaglutide in Colombian adults with T2DM, from a third-party payer perspective.MethodsNumbers needed to treat were calculated for different single and composite endpoints of the SUSTAIN 7 trial, annual costs for once weekly semaglutide 1.0 mg and dulaglutide 1.5 mg were extracted from the public SISMED database. With these inputs a cost of control model was developed, to obtain the annual cost of bringing one T2DM patient to relevant clinical outcomes by using semaglutide or dulaglutide.ResultsSemaglutide was considered cost-effective compared to dulaglutide across all pre-specified endpoints, even in the different scenarios evaluated in the sensitivity analyses, and in a particularly pronounced manner for weight loss outcomes. Semaglutide at a dose of 1.0 mg once-weekly was cost-effective compared to dulaglutide 1.5 mg across all outcomes in the short-term, making it an appropriate first-line choice in the treatment of T2DM when deciding between these two GLP-1 receptor agonists.ConclusionsThis is the first short-term cost-effectiveness study of semaglutide and dulaglutide in T2DM Colombian patients. Our modeled results suggest that once-weekly semaglutide represents a cost-effective option for treating individuals with T2DM in Colombia who are not achieving glycaemia control with metformin, and it would be expected to improve HbA1C, promote greater weight loss and reduce costs from a third-payer perspective compared with treatment with dulaglutide.

Project description:IntroductionDulaglutide is a recombinant glucagon-like peptide-1 immunoglobulin G4 Fc fusion protein approved for treating patients with type 2 diabetes (T2D). The aim of this study was to assess postprandial data over 4 weeks for dulaglutide (0.75 mg) versus placebo after a standardized test meal in Japanese patients with T2D.MethodsThe pharmacodynamic (PD) effects of once-weekly dulaglutide (0.75 mg) in Japanese patients with T2D on diet and exercise therapy (N = 12) were evaluated by assessing postprandial data up to week 4 in a phase 4, single-center, randomized, cross-over, single-blind, placebo-controlled study. The primary end point was the change in 4-h glucose area under the concentration versus time curve [AUC (0-4 h)] from baseline to week 4. Secondary end points included changes from baseline in other PD parameters (insulin, C-peptide, glucagon, and triglycerides) at weeks 1, 2, and 4 and the safety and tolerability of dulaglutide 0.75 mg. Continuous glucose monitoring (CGM) during the 1st week was performed as an exploratory measure in each treatment period.ResultsThe decrease in AUC (0-4 h) from baseline to week 4 following dulaglutide administration was statistically significant compared with placebo at weeks 1, 2, and 4 (P < 0.0001). Insulin and C-peptide levels were also significantly increased (P < 0.05) with dulaglutide versus placebo at weeks 2 and 4. There were no statistically significant differences between groups in glucagon and triglyceride levels. Daily average glucose concentrations were decreased on the day after the first administration of dulaglutide and remained at similar levels for 4 days. The incidence of treatment-emergent adverse events was slightly higher with dulaglutide versus placebo.ConclusionIn conclusion, dulaglutide decreased postprandial glucose from week 1 in Japanese patients with T2D, indicating that dulaglutide treatment is associated with favorable PD effects soon after treatment begins.Trial registrationClinicalTrials.gov identifier: NCT03315780.FundingEli Lilly Japan K.K. (Kobe, Japan).

Dataset Information

Change in pharmacodynamic variables following once-weekly tirzepatide treatment versus dulaglutide in Japanese patients with type 2 diabetes (SURPASS J-mono substudy).

Aim

Materials and methods

Results

Conclusions

Publications

Change in pharmacodynamic variables following once-weekly tirzepatide treatment versus dulaglutide in Japanese patients with type 2 diabetes (SURPASS J-mono substudy).

Similar Datasets

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