Recently, a new data from the phase 3a SCALET Obesity and Prediabetes trial were presented at The Endocrine Society's 97th Annual Meeting (ENDO), showing that adults with obesity or who are overweight with comorbidities who had lost 5 per cent of their body weight at 56 weeks (ie weight loss responders), demonstrated greater improvements across a range of efficacy outcomes with Saxenda (liraglutide 3 mg) treatment in combination with a reduced-calorie diet and increased physical activity, compared with those that had a weight loss of <5 per cent (ie non-responders).
In the SCALET Obesity and Prediabetes trial, 63.2 per cent of adults achieved a clinically meaningful body weight reduction of at least 5 per cent with Saxenda compared with 27.1 per cent on placebo (p<0.0001). The average weight loss for responders on Saxenda treatment was 11.7 per cent compared with 1.7 per cent for non-responders. For placebo treatment, average weight loss in responders was 10.0 per cent versus 0.1 per cent weight gain in non-responders. Saxenda treatment was associated with a greater reduction in waist circumference in responders, compared with non-responders (11.0 cm vs 3.3 cm).
In addition to weight loss, improvements across a number of secondary endpoints were also observed in the responder population (Saxenda and placebo). A greater improvement was seen in fasting plasma glucose (FPG) in Saxenda responders compared with placebo responders (-8.3 vs -2.8 mg/dl, respectively) as well as non-responders (-5.0 vs +1.1 mg/dl, respectively). In addition, treatment with Saxenda was associated with a greater reduction in systolic blood pressure (SBP) compared with placebo in both responders (-5.5 vs -3.4 mm Hg, respectively) and non-responders (-2.0 vs. -0.8 mm Hg, respectively). Improvements in physical health scores (as measured by the SF-36 questionnaire) were seen with Saxenda and placebo responders (+4.3 vs +4.1 points, respectively) compared with non-responders (+2.1 vs +1.3 points, respectively).
"These are important findings as they show that for adults with obesity or who are overweight with comorbidities, losing 5 per cent to 10 per cent of their body weight can help improve comorbidities, including fasting plasma glucose and blood pressure," says Dr Patrick O'Neil, Professor of Psychiatry and Behavioural Sciences at the Medical University of South Carolina and SCALET clinical trial investigator. "Those who responded, losing 5 per cent or more of their body weight, not only saw improvements in cardiometabolic risk factors but also in quality of life outcomes, compared with those who did not respond, for both liraglutide and placebo treatment."
Across the SCALET clinical development programme, Saxenda (liraglutide 3 mg) was generally well tolerated. The most common side effects observed were related to the gastrointestinal system. In the SCALET Obesity and Prediabetes trial, rates of adverse events were similar in both responders and non-responders. The number of adverse events leading to trial withdrawal was lower in responders compared with non-responders.
Obesity is a disease that requires chronic management. It is associated with serious comorbidities including type 2 diabetes, heart disease, obstructive sleep apnoea (OSA), certain types of cancer and a decreased life expectancy. The risk of morbidity and mortality increases with the severity of obesity, It is a complex and multifactorial disease that is influenced by genetic, physiological, environmental and psychological factors.
The global increase in the prevalence of obesity is a public health issue that has severe cost implications to healthcare systems. , In 2011-2012 in the US, approximately 35 per cent of adults, or nearly 80 million adults, live with obesity.
Saxenda is a once-daily glucagon-like peptide-1 (GLP-1) analogue with 97 per cent similarity to naturally occurring human GLP-1, a hormone that is released in response to food intake. Like human GLP-1, Saxenda regulates appetite and lowers body weight through decreased food intake. As with other GLP-1 receptor agonists, liraglutide stimulates insulin secretion and reduces glucagon secretion in a glucose-dependent manner. These effects can lead to a reduction of blood glucose. Saxenda was evaluated in the SCALET (Satiety and Clinical AdiposityLiraglutide Evidence in Nondiabetic and Diabetic people) phase 3 clinical trial programme, which involved more than 5,000 study participants who have obesity (BMI 30 kg/m2) or who are overweight (BMI ?27 kg/m2) with comorbidities.
Saxenda was approved by the FDA on 23 December 2014, as an adjunct to a reduced-calorie diet and increased physical activity for chronic weight management in adults with obesity (BMI 30 kg/m2) or who are overweight (BMI 27 kg/m2) with at least one weight-related comorbidity.
Saxenda received a positive opinion from the Committee for Medicinal Products for Human Use (CHMP) on 22 January 2015. In accordance with the EMA Centralised Procedure, a decision whether to grant marketing authorisation is taken by the European Commission within approximately 2 to 3 months.
The SCALET Obesity and Prediabetes trial is a randomised, double-blind, placebo-controlled, multinational trial in non-diabetic adults with obesity and non-diabetic adults who are overweight with comorbidities. There were 3,731 participants randomised to treatment with Saxenda (liraglutide 3 mg) or placebo in combination with reduced-calorie diet and increased physical activity. In addition, participants were further stratified to 56 weeks or 160 weeks of treatment based on prediabetes status at baseline screening.
The objectives of this trial were to demonstrate clinically meaningful weight loss at 56 weeks, as well as to investigate the long-term potential efficacy of Saxenda to delay the onset of type 2 diabetes in participants with prediabetes at baseline screening.
It is the largest of the phase 3a trials in the SCALET clinical development programme, which encompassed more than 5,000 adults with obesity or adults who are overweight with comorbidities.