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Efficacy and safety of once-weekly dulaglutide versus insulin glargine in mainly Asian patients with type 2 diabetes mellitus on metformin and/or a sulphonylurea: A 52-week open-label, randomized phase III trial.

ABSTRACT: AIM:To compare the efficacy and safety of once-weekly dulaglutide with that of insulin glargine in combination with metformin and/or a sulphonylurea in mainly Asian patients with type 2 diabetes mellitus (T2DM). MATERIALS AND METHODS:In this 52-week, randomized, parallel-arm open-label study, we enrolled patients aged ?18 years with T2DM for at least 6 months and a glycated haemoglobin (HbA1c) concentration ?53.0 mmol/mol (7.0%) and ?96.7 mmol/mol (11.0%). The primary outcome was change in HbA1c from baseline to week 26 to determine non-inferiority of dulaglutide 1.5 mg versus glargine. RESULTS:A total of 774 patients from China, South Korea, Mexico and Russia were randomly assigned (1:1:1) to dulaglutide 1.5 mg, dulaglutide 0.75 mg or glargine treatment groups. The patients' mean age was 55 years and the average T2DM duration was ~8 years. The least squares mean (SE) changes from baseline in HbA1c at 26 weeks were - 18.9 (0.73) mmol/mol (-1.73 [0.067]%) for dulaglutide 1.5 mg and -14.5 (0.73) mmol/mol (-1.33 [0.067]%) for dulaglutide 0.75 mg, compared with -12.7 (0.73) mmol/mol (-1.16 [0.067]%) for glargine. Statistical criteria for superiority were met with both dulaglutide 1.5 mg and dulaglutide 0.75 mg. More patients in the dulaglutide 1.5 and 0.75 mg groups achieved HbA1c target <53.0 mmol/mol (<7.0%) than in the glargine group at week 26 (P < 0.001 and P = 0.004, respectively). Body weight decreased with dulaglutide and increased with glargine. The incidence and rate of total hypoglycaemia were lower with dulaglutide versus glargine. Gastrointestinal adverse events, including diarrhoea and nausea, were the most frequently reported for patients taking dulaglutide. CONCLUSIONS:Once-weekly dulaglutide provides greater improvement in HbA1c, with weight loss and less hypoglycaemia, than once-daily insulin glargine in a population of mainly Asian patients with T2DM who had failed to achieve optimal glycaemic control on metformin and/or a sulphonylurea.

SUBMITTER: Wang W

PROVIDER: S-EPMC6585712 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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Efficacy and safety of once-weekly dulaglutide versus insulin glargine in mainly Asian patients with type 2 diabetes mellitus on metformin and/or a sulphonylurea: A 52-week open-label, randomized phase III trial.

Wang Weiqing W Nevárez Luis L Filippova Ekaterina E Song Ki Ho KH Tao Bei B Gu Liqun L Wang Feng F Li Pengfei P Yang Jun J

Diabetes, obesity & metabolism 20181007 2

<h4>Aim</h4>To compare the efficacy and safety of once-weekly dulaglutide with that of insulin glargine in combination with metformin and/or a sulphonylurea in mainly Asian patients with type 2 diabetes mellitus (T2DM).<h4>Materials and methods</h4>In this 52-week, randomized, parallel-arm open-label study, we enrolled patients aged ≥18 years with T2DM for at least 6 months and a glycated haemoglobin (HbA1c) concentration ≥53.0 mmol/mol (7.0%) and ≤96.7 mmol/mol (11.0%). The primary outcome was ...[more]

PMID: 30129089

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Project description:IntroductionThis 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.MethodsChange from baseline in glycated hemoglobin (HbA1c), fasting blood glucose (FBG) and body weight were analyzed by age (< 60 years, ≥ 60 years), gender (male, female), body weight (< 70 kg, ≥ 70 kg), BMI (< 25 kg/m2, ≥ 25 kg/m2), duration of diabetes (< 10 years, ≥ 10 years), baseline HbA1c (< 8.5%, ≥ 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.ResultsA 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 ≥ 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.ConclusionsIn 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 registrationClinicalTrials.gov Identifier: NCT01648582.

Project description:ObjectiveAmong patients with type 2 diabetes uncontrolled with metformin, exenatide once weekly (QW) plus dapagliflozin combination produced greater reductions in glycemia, weight, and systolic blood pressure (SBP) at 28 weeks than exenatide QW or dapagliflozin alone (DURATION-8). Here, we investigated the safety and maintenance of efficacy at 52 weeks, after a 24-week extension.Research design and methodsThis phase 3, multicenter, double-blind study randomized adults with type 2 diabetes (with glycated hemoglobin [HbA1c] 8.0-12.0% [64-108 mmol/mol] and on metformin ≥1,500 mg/day) to exenatide QW (2-mg subcutaneous injection) plus once-daily dapagliflozin (10-mg oral tablet), exenatide QW plus oral placebo, or dapagliflozin plus injected placebo. Extension-period P values were nominal.ResultsOf 1,375 patients screened, 695 were randomized (mean baseline HbA1c 9.3% [78 mmol/mol]); 81.2% completed the study, and 75.3% completed treatment. At 52 weeks, HbA1c reductions were greater with exenatide QW plus dapagliflozin (least squares mean change -1.75% [-19.1 mmol/mol]) versus exenatide QW (-1.38% [-15.1 mmol/mol]; P = 0.006) or dapagliflozin (-1.23% [-13.4 mmol/mol]; P < 0.001); mean HbA1c values were 6.9% (52 mmol/mol), 7.2% (55 mmol/mol), and 7.4% (57 mmol/mol), respectively. Weight and SBP reductions were greater with exenatide QW plus dapagliflozin (-3.31 kg and -4.5 mmHg) versus exenatide QW (-1.51 kg and -0.7 mmHg; both P < 0.001) but similar to those with dapagliflozin (-2.28 kg and -2.7 mmHg; P = 0.057 and P = 0.100, respectively). The exenatide QW plus dapagliflozin regimen was well tolerated with no unexpected safety findings; more patients treated with exenatide QW experienced gastrointestinal and injection site-related adverse events. No major hypoglycemia occurred.ConclusionsAmong patients with type 2 diabetes uncontrolled with metformin, exenatide QW plus dapagliflozin provided sustained improvements in glycemia, weight, and SBP over 52 weeks, with no unexpected safety findings.

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:The aim of this monocentric retrospective observational study was to evaluate the 18-month safety and effectiveness of GLP-1 receptor agonist (GLP-1 RA) dulaglutide (DU) 1.5 mg/once weekly as an add-on to metformin (MET) or MET plus conventional insulin secretagogues in a study cohort with excess body weight and type 2 diabetes (T2D). Comparative efficacy versus liraglutide (LIRA) 1.2-1.8 mg/once daily in a study sample naïve to GLP-1 RAs, frequency matching for age, gender, T2D duration, degree of glycemic impairment, cardiovascular comorbidities, and medications, was addressed as a secondary aim. Clinical and biochemical data for efficacy outcomes and information on drug discontinuation due to adverse events (AEs) were collected from digital records. Initial analysis included 126 overweight and obese T2D patients (48.4% females). Out of these, 13 discontinued DU due to moderate-severe gastrointestinal AEs after a mean follow-up of 6 (4 standard deviations (SD)) months, while 65 completed 18 months of continuous therapy. At 6 months, there was a significant mean HbA1c reduction of -0.85% (1.17 SD) with respect to baseline values (p < 0.001), which remained stable during 18 months follow-up. These results were accompanied by a moderate weight loss sustained over time, with a mean reduction of -2.0% (4.3 SD) at 6 months and -1.3% (4.8 SD) at 18 months (p = 0.091). At univariate analysis, a negative correlation between baseline body mass index (BMI) and risk of drug discontinuation due to gastrointestinal AEs was observed. The protective effect of obesity against drug discontinuation was confirmed by logistic regression analysis. Neither gender, nor age, nor T2D duration, nor concomitant conventional insulin secretagogue use, nor switching to DU from other GLP-1 RAs influenced its long-term effectiveness. However, higher baseline HbA1c values emerged as predictors of clinically relevant efficacy outcomes, either in terms of HbA1c reduction ≥ 0.5% or body weight loss ≥ 5%. The efficacy outcomes were corroborated by head-to-head comparison with LIRA, a GLP-1 RA with durable beneficial effects on glycemic control and body weight in real-world experiences. With the advantage of once-weekly administration, at 18-month follow-up, a significantly larger fraction of patients on DU therapy reached glycemic targets (HbA1c ≤ 7.0%) when compared to those on LIRA: from 14.8% at baseline (both groups) to 64.8% with DU and 42.6% with LIRA (p = 0.033). Although limited by a retrospective design and lack of constant up-titration for LIRA to the highest dose, these findings indicate that the beneficial responses to DU on a background of MET or MET plus insulin secretagogues are durable, especially in the presence of obesity and greater HbA1c impairment.

Project description:Objective:To evaluate the effects of once-weekly dulaglutide injection and once-daily glimepiride on glucose fluctuation in patients with type 2 diabetes mellitus (T2DM) using the Continuous Glucose Monitoring System (CGMS). Methods:A total of 23 patients with T2DM were randomly assigned into two groups for 26 weeks: the dulaglutide group (n = 13) and the glimepiride group (n = 10). 72-hour CGMS was applied to all patients: before and after the treatment. General clinical data were collected and measured, such as fasting blood glucose (FBG), glycosylated hemoglobin (HbA1c), tumor necrosis factor-? (TNF-?), 8-iso-prostaglandin F2? (8-iso-PGF2?), and interleukin-6 (IL-6). Results:HbA1c of the dulaglutide group was reduced from 8.38 ± 0.93% to 6.68 ± 0.73% after the treatment (P < 0.05); similarly, it was reduced from 7.91 ± 0.98% to 6.67 ± 0.74% (P < 0.05) in the glimepiride group. The levels of serum 8-iso-PGF2?, TNF-?, and IL-6 all decreased significantly in both groups after treatment, and there was no significant difference found between the two groups (P > 0.05). The Mean Blood Glucose (MBG) of the two groups declined significantly after therapy (P < 0.05). However, the Standard Deviation of Blood Glucose (SDBG) decreased significantly only in the dulaglutide group (from 2.57 ± 0.74 mmol/L to 1.98 ± 0.74 mmol/L, P < 0.05). There were no significant changes of Mean Amplitude of Glycemic Excursion (MAGE) and Absolute Means of Daily Difference (MODD) after treatment in both groups. Furthermore, no statistically significant difference was found between the two groups in MBG, SDBG, MAGE, and MODD (P > 0.05). The percentage time (PT) (>10?mmol/L and 3.9-10?mmol/L) of the two groups was significantly changed after the treatment (P < 0.05). However, this was not seen in the PT < 3.9 mmol/L after the treatment (P > 0.05). Conclusion:Once-weekly dulaglutide injection has the same effectiveness as daily glimepiride on lowering blood glucose and decreasing oxidation stress and inflammation and is more effective in controlling glucose fluctuation as compared with glimepiride. This trial is registered with ClinicalTrials.gov NCT01644500.

Dataset Information

Efficacy and safety of once-weekly dulaglutide versus insulin glargine in mainly Asian patients with type 2 diabetes mellitus on metformin and/or a sulphonylurea: A 52-week open-label, randomized phase III trial.

Publications

Efficacy and safety of once-weekly dulaglutide versus insulin glargine in mainly Asian patients with type 2 diabetes mellitus on metformin and/or a sulphonylurea: A 52-week open-label, randomized phase III trial.

Similar Datasets

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