Phase 3a liraglutide 3 mg trial demonstrated significant weight loss and improved cardiovascular risk factors in adults with obesity and type 2 diabetes compared with placebo
Posted: 23 June 2014 | Novo Nordisk | No comments yet
New data from the phase 3a SCALE™ Diabetes trial were presented at the International Congress of Endocrinology and the Endocrine Society’s meeting, investigating the effect of liraglutide 3 mg in adults…
Today, new data from the phase 3a SCALE™ Diabetes trial were presented at the International Congress of Endocrinology (ICE) and the Endocrine Society’s meeting (ENDO), investigating the effect of liraglutide 3 mg in adults with obesity and type 2 diabetes or who were overweight with type 2 diabetes. Data demonstrated that, at 56 weeks, in addition to clinically meaningful weight loss, treatment with liraglutide 3 mg provided statistically significantly greater improvements in risk factors for cardiovascular (CV) disease, compared with placebo, in combination with diet and physical activity.
All treatment groups followed a reduced-calorie diet and increased physical activity programme. At 56 weeks of treatment, the SCALE™ Diabetes trial demonstrated that adults treated with liraglutide 3 mg achieved significantly greater mean weight loss of 5.9% compared with 2.0% with placebo (p<0.0001). The 3.0 mg dose also produced more weight loss than liraglutide 1.8 mg (4.6%, p=0.0024). Waist circumference was also significantly reduced with both liraglutide 3 mg (–6.0 cm) and liraglutide 1.8 mg (–4.9 cm), compared with placebo (–2.8 cm, p=0.0004).
“Cardiovascular disease is a major concern in people with obesity and type 2 diabetes,” said Dr. Ralph DeFronzo, Deputy Director of the Texas Diabetes Institute, San Antonio, and a SCALE™ Diabetes trial investigator. “The results from the SCALE™ Diabetes trial indicate that treatment with liraglutide 3 mg may lead to improvements across a number of cardiovascular disease risk factors, including cholesterol and blood pressure, which may be especially important for this patient population.”
A moderate weight loss of 5 to 10% has been shown to reduce risk factors for CV disease in people with obesity.In the SCALE™ Diabetes trial, liraglutide 3 mg and 1.8 mg significantly reduced systolic blood pressure by 3.0 and 3.1 mmHg respectively, compared with 0.4 mm Hg with placebo (p<0.05). No significant difference between treatments was observed in diastolic blood pressure. Compared with baseline, liraglutide 3 mg significantly improved total cholesterol (–4%) and fasting lipid levels, including very low-density lipoproteins, high-density lipoproteins and triglycerides (–13%, +3% and –14%, respectively, p<0.05). Liraglutide 1.8 mg had no significant effect on cholesterol or lipid levels.
Liraglutide 3 mg and 1.8 mg significantly improved levels of the inflammatory marker C-reactive protein (CRP) by –27% and –25% compared with placebo (p=0.0002). CRP is elevated in people with obesity and is a good predictor of CV disease. Compared with placebo, liraglutide 3 mg additionally improved CV risk factors, including the blood clot risk factor plasminogen activator inhibitor-1 (–24%, p=0.0004) and the urinary albumin/creatinine ratio (–20%, p=0.0086), which is a common marker for chronic kidney disease.
The most frequently reported side effects were gastrointestinal disorders (driven by nausea and diarrhoea), and occurred in 65% of people treated with liraglutide 3 mg compared with 56% with liraglutide 1.8 mg and 39% with placebo. The most common adverse events occurring in more than 5% of people treated with liraglutide 3 mg included hypoglycaemia, decreased appetite, abdominal distension, abdominal pain, dyspepsia, flatulence, vomiting, constipation, nasopharyngitis (usually referred to as the common cold), upper respiratory tract infection, influenza, back pain, musculoskeletal pain, arthralgia, headache, dizziness, fatigue and increased lipase. The most frequent side effects leading to withdrawal from the liraglutide 3 mg treatment group were gastrointestinal disorders (5.7%).
In December 2013, based on the results of the SCALE™ clinical development programme, Novo Nordisk submitted a New Drug Application and a Marketing Authorisation Application to the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA), respectively, for liraglutide 3 mg for chronic weight management in adults who have obesity (BMI =30 kg/m2), or are overweight (BMI =27 kg/m2) with comorbidities, as an adjunct to a reduced-calorie diet and increased physical activity. These applications are under review.
Liraglutide is currently available in the US and other countries at lower doses under the brand name Victoza® for treatment of adults with type 2 diabetes mellitus to improve blood glucose control. Victoza® is not approved for weight management.
FDA guidance recommends that any investigational product being developed for weight management should be investigated in people with type 2 diabetes, as overweight and obese patients with type 2 diabetes often respond less favourably to weight-management medications.7 The FDA requested the inclusion of liraglutide 1.8 mg (Victoza®) in the SCALE™ Diabetes study to bridge to the safety and efficacy data for Victoza® in the treatment of adults with type 2 diabetes.