a-t 2016; 47: 67

LEADER study with liraglutide (VICTOZA) - first positive data for a GLP-1 agonist in type 2 diabetes:* following the EMPA-REG-OUTCOME study (1) with empagliflozin (JARDIANCE; a-t 2015; 46: 95-7, see also a-t 2016; 47: 65-6) a second long-term trial is now being published on the cardiovascular safety of a new antidiabetic agent for the management of type 2 diabetes, the results of which are favourable for the investigational medicinal product: The LEADER study (2) with the glucagon-like peptide (GLP)-1 agonist liraglutide (VICTOZA; a-t 2009; 40: 80-2). 9,340 patients with an average age of 64 years, suffering from type 2 diabetes for 13 years, on average, with an HbA1c value of at least 7% (averaging 8.7%) and increased cardiovascular risk (due to previous cardiovascular conditions such as myocardial infarction, at least moderate renal insufficiency or cardiovascular risk factors such as hypertension plus left ventricular hypertrophy) took part. In addition to their previous antidiabetic medication**, the patients injected 0.6 mg to 1.8 mg liraglutide or placebo every day, depending on tolerance. Compared to placebo, liraglutide slightly reduced the HbA1c value (by 0.4% after 36 months) and systolic blood pressure (by 1.2 mmHg). Greater weight loss was also observed during administration of the active drug (averaging 2.3 kg). Primary endpoint events (myocardial infarction, stroke or death from cardiovascular causes) occurred significantly less often with liraglutide (13% vs. 14.9%; number needed to treat [NNT] = 200/year). All three individual components were reduced but a significant reduction was only recorded in relation to death from cardiovascular causes (4.7% vs. 6%; NNT = 292/year). Overall mortality was also reduced with liraglutide (8.2% vs. 9.6%; NNT = 271/year) (2). As with empagliflozin, it is unclear as to which mechanisms of action of liraglutide could have caused the effects. According to sub-group analyses, only patients with a previous cardiovascular disease or renal insufficiency benefit from this therapy. The effect also appears to be greater in subjects with a high body mass index (2). GLP-1 agonists such as liraglutide are relatively new antidiabetic drugs and only limited testing has been carried out to date. The LEADER study is the first positive study with a GLP-1 agonist. A study published last year on lixisenatide, which is no longer available in Germany (commercially unavailable: LYXUMIA) did not find a cardiovascular benefit with this GLP-1 agonist (3). In our opinion, the results should be corroborated by subsequent studies before liraglutide can be recommended for cardiovascular prophylaxis in type 2 diabetes, -Ed.

    (R = randomised trial)
R 1 ZINMAN, B. et al.: N. Engl. J. Med. 2015; 373: 2117-28
R 2 MARSO, S.P. et al.: N. Engl. J. Med., publ. online 13 June 2016; doi: 10.1056/NEJMoa1603827
R 3 PFEFFER, M.A. et al.: N. Engl. J. Med. 2015; 373: 2247-57

  * Extended version (in German) see e a-t 7/2016
  ** Patients were primarily pretreated with metformin (GLUCOPHAGE, generics; 76%), sulfonylureas (51%) and insulin (45%). To optimise basal medication, all antidiabetics were permitted except for other GLP-1 agonists, dipeptidyl peptidase-4 inhibitors and pramlintide (SYMLIN) for which a marketing authorisation has been granted in the USA (2).

  Caution: less than five years on the market or under additional monitoring according to the European Medicines Agency

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