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Semaglutide versus dulaglutide once weekly in patients with type 2 diabetes (SUSTAIN 7): a randomised, open-label, phase 3b trial.

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Citation: The Lancet Diabetes & Endocrinology. 6(4):275-286, 2018 04.PMID: 29397376Institution: MedStar Health Research InstituteForm of publication: Journal ArticleMedline article type(s): Journal ArticleSubject headings: *Diabetes Mellitus, Type 2/dt [Drug Therapy] | *Glucagon-Like Peptides/aa [Analogs & Derivatives] | *Hypoglycemic Agents/tu [Therapeutic Use] | *Immunoglobulin Fc Fragments/tu [Therapeutic Use] | *Recombinant Fusion Proteins/tu [Therapeutic Use] | Blood Glucose/an [Analysis] | Body Weight | Female | Glucagon-Like Peptides/tu [Therapeutic Use] | Humans | Male | Middle Aged | PrognosisYear: 2018 ISSN:

2213-8587

Name of journal: The lancet. Diabetes & endocrinologyAbstract: BACKGROUND: Despite common mechanisms of actions, glucagon-like peptide-1 receptor agonists differ in structure, pharmacokinetic profile, and clinical effects. This head-to-head trial compared semaglutide with dulaglutide in patients with inadequately controlled type 2 diabetes.Copyright (c) 2018 Elsevier Ltd. All rights reserved.FINDINGS: Between Jan 6, 2016, and June 22, 2016, 1201 patients were randomly assigned to treatment; of these, 301 were exposed to semaglutide 0.5 mg, 299 to dulaglutide 0.75 mg, 300 to semaglutide 1.0 mg, and 299 to dulaglutide 1.5 mg. 72 (6%) patients withdrew from the trial (22 receiving semaglutide 0.5 mg, 13 receiving dulaglutide 0.75 mg, 21 receiving semaglutide 1.0 mg, and 16 receiving dulaglutide 1.5 mg). From overall baseline mean, mean percentage HbA1c was reduced by 1.5 (SE 0.06) percentage points with semaglutide 0.5 mg versus 1.1 (0.05) percentage points with dulaglutide 0.75 mg (estimated treatment difference [ETD] -0.40 percentage points [95% CI -0.55 to -0.25]; p<0.0001) and by 1.8 (0.06) percentage points with semaglutide 1.0 mg versus 1.4 (0.06) percentage points with dulaglutide 1.5 mg (ETD -0.41 percentage points [-0.57 to -0.25]; p<0.0001). From overall baseline mean, mean bodyweight was reduced by 4.6 kg (SE 0.28) with semaglutide 0.5 mg compared with 2.3 kg (0.27) with dulaglutide 0.75 mg (ETD -2.26 kg [-3.02 to -1.51]; p<0.0001) and by 6.5 kg (0.28) with semaglutide 1.0 mg compared with 3.0 kg (0.27) with dulaglutide 1.5 mg (ETD -3.55 kg [-4.32 to -2.78]; p<0.0001). Gastrointestinal disorders were the most frequently reported adverse event, occurring in 129 (43%) of 301 patients receiving semaglutide 0.5 mg, 133 (44%) of 300 patients receiving semaglutide 1.0 mg, 100 (33%) of 299 patients receiving dulaglutide 0.75 mg, and in 143 (48%) of 299 patients receiving dulaglutide 1.5 mg. Gastrointestinal disorders were also the most common reason for discontinuing treatment with semaglutide and dulaglutide. There were six fatalities: one in each semaglutide group and two in each dulaglutide group.FUNDING: Novo Nordisk.INTERPRETATION: At low and high doses, semaglutide was superior to dulaglutide in improving glycaemic control and reducing bodyweight, enabling a significantly greater number of patients with type 2 diabetes to achieve clinically meaningful glycaemic targets and weight loss, with a similar safety profile.METHODS: This was an open-label, parallel-group, phase 3b trial done at 194 hospitals, clinical institutions or private practices in 16 countries. Eligible patients were aged 18 years or older and had type 2 diabetes with HbA1c 7.0-10.5% (53.0-91.0 mmol/mol) on metformin monotherapy. Patients were randomly assigned (1:1:1:1) by use of an interactive web-response system to once a week treatment with either semaglutide 0.5 mg, dulaglutide 0.75 mg, semaglutide 1.0 mg, or dulaglutide 1.5 mg subcutaneously. The primary endpoint was change from baseline in percentage HbA1c; the confirmatory secondary endpoint was change in bodyweight, both at week 40. The primary analysis population included all randomly assigned patients exposed to at least one dose of trial product obtained while on treatment and before the onset of rescue medication. The safety population included all randomly assigned patients exposed to at least one dose of trial product obtained while on treatment. The trial was powered for HbA1c non-inferiority (margin 0.4%) and bodyweight superiority. This trial is registered with ClinicalTrials.gov, number NCT02648204.All authors: Andreassen C, Aroda VR, Lingvay I, Ludemann J, Navarria A, Pratley RE, SUSTAIN 7 investigators, Viljoen AFiscal year: FY2018Digital Object Identifier:

https://dx.doi.org/10.1016/S2213-8587(18)30024-X

Date added to catalog: 2018-02-20

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Holdings
Item type	Current library	Collection	Call number	Status	Date due	Barcode
Journal Article	MedStar Authors Catalog	Article	29397376	Available		29397376

BACKGROUND: Despite common mechanisms of actions, glucagon-like peptide-1 receptor agonists differ in structure, pharmacokinetic profile, and clinical effects. This head-to-head trial compared semaglutide with dulaglutide in patients with inadequately controlled type 2 diabetes.

FINDINGS: Between Jan 6, 2016, and June 22, 2016, 1201 patients were randomly assigned to treatment; of these, 301 were exposed to semaglutide 0.5 mg, 299 to dulaglutide 0.75 mg, 300 to semaglutide 1.0 mg, and 299 to dulaglutide 1.5 mg. 72 (6%) patients withdrew from the trial (22 receiving semaglutide 0.5 mg, 13 receiving dulaglutide 0.75 mg, 21 receiving semaglutide 1.0 mg, and 16 receiving dulaglutide 1.5 mg). From overall baseline mean, mean percentage HbA1c was reduced by 1.5 (SE 0.06) percentage points with semaglutide 0.5 mg versus 1.1 (0.05) percentage points with dulaglutide 0.75 mg (estimated treatment difference [ETD] -0.40 percentage points [95% CI -0.55 to -0.25]; p<0.0001) and by 1.8 (0.06) percentage points with semaglutide 1.0 mg versus 1.4 (0.06) percentage points with dulaglutide 1.5 mg (ETD -0.41 percentage points [-0.57 to -0.25]; p<0.0001). From overall baseline mean, mean bodyweight was reduced by 4.6 kg (SE 0.28) with semaglutide 0.5 mg compared with 2.3 kg (0.27) with dulaglutide 0.75 mg (ETD -2.26 kg [-3.02 to -1.51]; p<0.0001) and by 6.5 kg (0.28) with semaglutide 1.0 mg compared with 3.0 kg (0.27) with dulaglutide 1.5 mg (ETD -3.55 kg [-4.32 to -2.78]; p<0.0001). Gastrointestinal disorders were the most frequently reported adverse event, occurring in 129 (43%) of 301 patients receiving semaglutide 0.5 mg, 133 (44%) of 300 patients receiving semaglutide 1.0 mg, 100 (33%) of 299 patients receiving dulaglutide 0.75 mg, and in 143 (48%) of 299 patients receiving dulaglutide 1.5 mg. Gastrointestinal disorders were also the most common reason for discontinuing treatment with semaglutide and dulaglutide. There were six fatalities: one in each semaglutide group and two in each dulaglutide group.

FUNDING: Novo Nordisk.

INTERPRETATION: At low and high doses, semaglutide was superior to dulaglutide in improving glycaemic control and reducing bodyweight, enabling a significantly greater number of patients with type 2 diabetes to achieve clinically meaningful glycaemic targets and weight loss, with a similar safety profile.

METHODS: This was an open-label, parallel-group, phase 3b trial done at 194 hospitals, clinical institutions or private practices in 16 countries. Eligible patients were aged 18 years or older and had type 2 diabetes with HbA1c 7.0-10.5% (53.0-91.0 mmol/mol) on metformin monotherapy. Patients were randomly assigned (1:1:1:1) by use of an interactive web-response system to once a week treatment with either semaglutide 0.5 mg, dulaglutide 0.75 mg, semaglutide 1.0 mg, or dulaglutide 1.5 mg subcutaneously. The primary endpoint was change from baseline in percentage HbA1c; the confirmatory secondary endpoint was change in bodyweight, both at week 40. The primary analysis population included all randomly assigned patients exposed to at least one dose of trial product obtained while on treatment and before the onset of rescue medication. The safety population included all randomly assigned patients exposed to at least one dose of trial product obtained while on treatment. The trial was powered for HbA1c non-inferiority (margin 0.4%) and bodyweight superiority. This trial is registered with ClinicalTrials.gov, number NCT02648204.

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