赛马鲁肽
医学
2型糖尿病
安慰剂
杜拉鲁肽
糖尿病
随机对照试验
相伴的
临床试验
内科学
利拉鲁肽
替代医学
艾塞那肽
内分泌学
病理
作者
Bernard Zinman,Vaishali Bhosekar,Robert S. Busch,Ingrid Holst,Bernhard Ludvik,Desirée Thielke,James Thrasher,Vincent Woo,Athena Philis‐Tsimikas
标识
DOI:10.1016/s2213-8587(19)30066-x
摘要
Summary
Background
Semaglutide is a once-weekly glucagon-like peptide-1 (GLP-1) analogue for type 2 diabetes. Few clinical trials have reported on the concomitant use of GLP-1 receptor agonists with sodium-glucose cotransporter-2 (SGLT-2) inhibitors. We aimed to investigate the efficacy and safety of semaglutide when added to SGLT-2 inhibitor therapy in patients with inadequately controlled type 2 diabetes. Methods
The SUSTAIN 9 double-blind, parallel-group trial was done at 61 centres in six countries (Austria, Canada, Japan, Norway, Russia, and the USA). Adults with type 2 diabetes and HbA1c 7·0–10·0% (53–86 mmol/mol), despite at least 90 days of treatment with an SGLT-2 inhibitor, were randomly assigned (1:1) to receive subcutaneous semaglutide 1·0 mg or volume-matched placebo once weekly for 30 weeks, after a dose-escalation schedule of 4 weeks of 0·25 mg semaglutide or placebo and 4 weeks of 0·5 mg semaglutide or placebo. Existing antidiabetic medications, including SGLT-2 inhibitor treatment, were continued for the duration of the trial. Rescue medication, defined as intensification of background antidiabetic treatment or the initiation of new glucose-lowering medications, could be given to patients meeting specific criteria at the discretion of the investigator. The primary outcome was change in HbA1c from baseline at week 30, assessed in the full analysis set (all patients randomly allocated to treatment) using on-treatment data collected before rescue medication was started. The confirmatory secondary outcome was change in bodyweight from baseline to week 30. Safety was also assessed in the safety analysis set (all patients who received at least one dose of treatment). The trial was registered with ClinicalTrials.gov (NCT03086330). Findings
Between March 15, and Dec 4, 2017, 302 patients were enrolled and randomly assigned to receive semaglutide 1·0 mg or placebo (full analysis set), of whom 301 received at least one dose of treatment (safety analysis set). One patient was assigned to semaglutide but was not treated (reason unknown). 294 (97·4%) patients completed the trial and 267 (88·4%) completed treatment. Baseline characteristics were generally comparable between groups. In addition to randomised medication and SGLT-2 inhibitor, 216 (71·5%) patients were taking metformin and 39 (12·9%) were taking sulphonylurea. Patients given semaglutide had greater reductions in HbA1c (estimated treatment difference −1·42% [95% CI −1·61 to −1·24]; −15·55 mmol/mol [–17·54 to −13·56]) and bodyweight (−3·81 kg [–4·70 to −2·93]) versus those randomised to placebo (both p<0·0001). 356 adverse events were reported by 104 (69·3%) patients in the semaglutide group, and 247 adverse events were reported by 91 (60·3%) patients in the placebo group. Gastrointestinal adverse events were most common and were reported in 56 (37·3%) patients in the semaglutide group and 20 (13·2%) in the placebo group. Serious adverse events occurred in seven (4·7%) patients in the semaglutide group and six (4·0%) in the placebo group. Severe or blood glucose-confirmed hypoglycaemic events were reported in four patients on semaglutide (2·7%). 16 patients stopped treatment early because of an adverse event, 13 of whom were in the semaglutide group. There were no deaths during the trial. Interpretation
Adding semaglutide to SGLT-2 inhibitor therapy significantly improves glycaemic control and reduces bodyweight in patients with inadequately controlled type 2 diabetes, and is generally well tolerated. Funding
Novo Nordisk.
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