Dataset Information

Liraglutide vs insulin glargine and placebo in combination with metformin and sulfonylurea therapy in type 2 diabetes mellitus (LEAD-5 met+SU): a randomised controlled trial.

ABSTRACT: The aim of the study was to compare the efficacy and safety of liraglutide in type 2 diabetes mellitus vs placebo and insulin glargine (A21Gly,B31Arg,B32Arg human insulin), all in combination with metformin and glimepiride.This randomised (using a telephone or web-based randomisation system), parallel-group, controlled 26 week trial of 581 patients with type 2 diabetes mellitus on prior monotherapy (HbA(1c) 7.5-10%) and combination therapy (7.0-10%) was conducted in 107 centres in 17 countries. The primary endpoint was HbA(1c). Patients were randomised (2:1:2) to liraglutide 1.8 mg once daily (n = 232), liraglutide placebo (n = 115) and open-label insulin glargine (n = 234), all in combination with metformin (1 g twice daily) and glimepiride (4 mg once daily). Investigators, participants and study monitors were blinded to the treatment status of the liraglutide and placebo groups at all times.The number of patients analysed as intention to treat were: liraglutide n = 230, placebo n = 114, insulin glargine n = 232. Liraglutide reduced HbA(1c) significantly vs glargine (1.33% vs 1.09%; -0.24% difference, 95% CI 0.08, 0.39; p = 0.0015) and placebo (-1.09% difference, 95% CI 0.90, 1.28; p < 0.0001). There was greater weight loss with liraglutide vs placebo (treatment difference -1.39 kg, 95% CI 2.10, 0.69; p = 0.0001), and vs glargine (treatment difference -3.43 kg, 95% CI 4.00, 2.86; p < 0.0001). Liraglutide reduced systolic BP (-4.0 mmHg) vs glargine (+0.5 mmHg; -4.5 mmHg difference, 95% CI 6.8, -2.2; p = 0.0001) but not vs placebo (p = 0.0791). Rates of hypoglycaemic episodes (major, minor and symptoms only, respectively) were 0.06, 1.2 and 1.0 events/patient/year, respectively, in the liraglutide group (vs 0, 1.3, 1.8 and 0, 1.0, 0.5 with glargine and placebo, respectively). A slightly higher number of adverse events (including nausea at 14%) were reported with liraglutide, but only 9.8% of participants in the group receiving liraglutide developed anti-liraglutide antibodies.Liraglutide added to metformin and sulfonylurea produced significant improvement in glycaemic control and bodyweight compared with placebo and insulin glargine. The difference vs insulin glargine in HbA(1c) was within the predefined non-inferiority margin.ClinicalTrials.gov NCT00331851.The study was funded by Novo Nordisk A/S.

SUBMITTER: Russell-Jones D

PROVIDER: S-EPMC2744824 | biostudies-literature | 2009 Oct

REPOSITORIES: biostudies-literature

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Liraglutide vs insulin glargine and placebo in combination with metformin and sulfonylurea therapy in type 2 diabetes mellitus (LEAD-5 met+SU): a randomised controlled trial.

Russell-Jones D D Vaag A A Schmitz O O Sethi B K BK Lalic N N Antic S S Zdravkovic M M Ravn G M GM Simó R R

Diabetologia 20090814 10

<h4>Aims/hypothesis</h4>The aim of the study was to compare the efficacy and safety of liraglutide in type 2 diabetes mellitus vs placebo and insulin glargine (A21Gly,B31Arg,B32Arg human insulin), all in combination with metformin and glimepiride.<h4>Methods</h4>This randomised (using a telephone or web-based randomisation system), parallel-group, controlled 26 week trial of 581 patients with type 2 diabetes mellitus on prior monotherapy (HbA(1c) 7.5-10%) and combination therapy (7.0-10%) was co ...[more]

PMID: 19688338

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Project description:ImportanceMetformin may have a protective association against developing osteoarthritis (OA), but robust epidemiological data are lacking.ObjectiveTo determine the risk of OA and joint replacement in individuals with type 2 diabetes treated with metformin compared with a sulfonylurea.Design, setting, and participantsThis retrospective cohort study used claims data from the Optum deidentified Clinformatics Data Mart Database between December 2003 and December 2019. Participants included individuals aged 40 years or older with at least 1 year of continuous enrollment and type 2 diabetes. Individuals with type 1 diabetes or a prior diagnosis of OA, inflammatory arthritis, or joint replacement were excluded. Time-conditional propensity score matching was conducted using age, sex, race, Charlson comorbidity score, and treatment duration to create a prevalent new-user cohort. Data were analyzed from April to December 2021.ExposuresTreatment with metformin or a sulfonylurea.Main outcomes and measuresThe outcomes of interest were incident OA and joint replacement. Cox proportional hazard models were used to calculate adjusted hazard ratios (aHRs) of incident OA and joint replacement. In a sensitivity analysis, individuals only ever treated with metformin were compared with individuals only ever treated with a sulfonylurea, allowing for longer-term follow up of the outcome (even after stopping the medication of interest).ResultsAfter time-conditional propensity score matching, the metformin and control groups each included 20 937 individuals (mean [SD] age 62.0 [11.5] years; 24 379 [58.2%] males). In the adjusted analysis, the risk of developing OA was reduced by 24% for individuals treated with metformin compared with a sulfonylurea (aHR, 0.76; 95% CI, 0.68-0.85; P < .001), but there was no significant difference for risk of joint replacement (aHR, 0.80; 95% CI, 0.50-1.27; P = .34). In the sensitivity analysis, the risk of developing OA remained lower in individuals treated with metformin compared with a sulfonylurea (aHR, 0.77; 95% CI, 0.65-0.90; P < .001) and the risk of joint replacement remained not statistically significant (aHR, 1.04; 95% CI, 0.60-1.82; P = .89).Conclusions and relevanceIn this cohort study of individuals with diabetes, metformin treatment was associated with a significant reduction in the risk of developing OA compared with sulfonylurea treatment. These results further support preclinical and observational data that suggest metformin may have a protective association against the development of OA; future interventional studies with metformin for the treatment or prevention of OA should be considered.

Project description:IntroductionThis study assessed the safety and efficacy of ertugliflozin (an oral sodium-glucose cotransporter 2 inhibitor) vs. glimepiride in patients with type 2 diabetes mellitus (T2DM) inadequately controlled on metformin.MethodsThis phase III, double-blind, non-inferiority study (NCT01999218) randomized patients with HbA1c ≥ 7.0% and ≤ 9.0% on stable metformin ≥ 1500 mg/day 1:1:1 to ertugliflozin 15 or 5 mg once-daily (QD), or glimepiride (titrated from 1 mg QD). The primary hypothesis was that ertugliflozin 15 mg was non-inferior to glimepiride on HbA1c (non-inferiority criterion: upper bound of the 95% confidence interval [CI] about the treatment difference < 0.3%).ResultsMean baseline HbA1c of randomized patients (N = 1326) was 7.8%. Mean and median doses of glimepiride were 3.0 mg/day throughout the study. At week 52, the least squares mean change (95% CI) from baseline in HbA1c was - 0.6% (- 0.7, - 0.5), - 0.6% (- 0.6, - 0.5), and - 0.7% (- 0.8, - 0.7) in the ertugliflozin 15 mg, ertugliflozin 5 mg, and glimepiride groups, respectively. The between-group difference for ertugliflozin 15 mg and glimepiride of 0.1% (- 0.0, 0.2) met the pre-specified non-inferiority criterion. Relative to glimepiride, greater body weight and systolic blood pressure (SBP) reductions were observed with ertugliflozin. The overall incidence of adverse events (AEs) was similar across groups. The incidence of symptomatic hypoglycemia and genital mycotic infection (GMI) were, respectively, lower and higher with ertugliflozin relative to glimepiride. The incidences of urinary tract infection and hypovolemia AEs were not meaningfully different among the groups.ConclusionsErtugliflozin 15 mg was non-inferior to glimepiride in reducing HbA1c when added to metformin in patients with T2DM. Ertugliflozin had an acceptable safety profile and resulted in less hypoglycemia and more GMIs than glimepiride.Clinical trial registrationClinicaltrials.gov NCT01999218.

Dataset Information

Liraglutide vs insulin glargine and placebo in combination with metformin and sulfonylurea therapy in type 2 diabetes mellitus (LEAD-5 met+SU): a randomised controlled trial.

Publications

Liraglutide vs insulin glargine and placebo in combination with metformin and sulfonylurea therapy in type 2 diabetes mellitus (LEAD-5 met+SU): a randomised controlled trial.

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