A new analysis of the STEP trails carried out by semaglutide manufacturer Novo Nordisk has analysed various trials to show the safety and efficacy of the obesity drug semaglutide in older adults (over 65 years), and found similar efficacy and safety as in the general trial populations . The study is by Prof Luca Busetto from the University of Padova in Italy and colleagues including from Novo Nordisk, who sponsor this new study.
Individuals of advanced age with obesity represent a vulnerable group, often presenting with comorbidities and frailty, and being at risk of adverse events (AEs). Information on the use of glucagon-like peptide-1 (GLP-1) receptor agonists including semaglutide in this population is limited; therefore, the authors decided assessed the efficacy and safety of once-weekly subcutaneous semaglutide 2.4 mg in individuals aged 65 years and over.
The analysis pooled together data from the STEP 1, 3, 4, 5, 8 and 9 trials (only in people with obesity or overweight, not diabetes, because weight loss in obesity drug trials is always lower in people with diabetes than without – thus results cannot be compared or mixed). It included participants aged ≥65 years with body mass index of at least 30 kg/m², or at least 27 kg/m² and at least 1 obesity-related complication (without diabetes) who were randomised to receive semaglutide 2.4 mg or placebo. All participants received lifestyle intervention and, in STEP 3, intensive behavioural therapy. Endpoints were assessed from baseline to week 68 and included percentage change in body weight; proportion of participants achieving categorical body weight reductions (≥10%, ≥15%, ≥20%); change in waist circumference; proportion of participants achieving waist to height ratio (WHtR) <0.53; shift in BMI category; and changes in cardiometabolic risk factors (glucose parameters, blood pressure, serum lipids and hs-CRP). Adverse events (AEs) were also assessed.
Of the total population in the selected trials (N=4523), 358 participants (8%) were aged 65 years or older and included in the analysis (semaglutide 2.4 mg, n=248; placebo, n=110), with most (90%) being aged 65–74 years (and the others 75 years and over). Across the pooled semaglutide and placebo groups at baseline, mean age was 69 years, bodyweight was 99.0 kg, BMI was 36.6 kg/m² and waist circumference was 115 cm; 72% were female.
At week 68, there was a mean −15.4% change in body weight for semaglutide 2.4 mg vs −5.1% for placebo, and a mean −14.3 cm vs −6.0 cm change in waist circumference, respectively. Proportions of participants achieving body weight reduction thresholds in the semaglutide 2.4 mg vs placebo groups were 66.5% vs 15.5% (at least 10%), 46.8% vs 6.4% (at least 15%) and 28.6% vs 2.7% (at least 20%), respectively.
In the semaglutide 2.4 mg group, 11.3% achieved a WHtR <0.53, compared with 4.5% with placebo. A greater proportion of semaglutide-treated participants improved their BMI category from baseline to week 68 compared with placebo (see Figure full abstract). A BMI of <27 kg/m² (so called healthy weight) was achieved by 27.0% of participants in the semaglutide group vs 5.5% in the placebo group; and the proportion of elderly patients in the overweight and obesity class I, II and III categories all fell in the semaglutide group at week 68 due to the increase in participants who had reached a healthy weight.
For participants achieving both a BMI of 27 or less and a WHtR of <0.53 these values were 10.5% vs 2.7%, respectively. Greater improvements in cardiometabolic risk factors were observed with semaglutide 2.4 mg vs placebo (see Table full abstract), including blood pressure, blood fats, cholesterol and glycated haemoglobin (HbA1c – a measure of blood sugar control used in diagnosis of diabetes).
Proportions of participants experiencing AEs and serious AEs in the semaglutide 2.4 mg vs placebo groups were similar for AEs overall (89.1% vs 84.5%), but higher for semaglutide re: serious AEs - 19.0% vs 12.7%, respectively. Constipation and dizziness rates (known side effects of this class of drug) were higher with semaglutide, while fractures and hypoglycaemia were comparable to placebo, both affecting less than 1% in each group.
Dr Busetto concludes: "In this analysis of individuals with obesity aged 65 years and older, semaglutide reduced body weight and improved cardiometabolic risk factors compared with placebo, and the safety and efficacy profile of semaglutide was consistent with that reported in the STEP programme."
He adds: "In many countries, including many high-income countries, the majority of the cases of excess weight actually occur in adults aged 65 years and over, representing a major driver for obesity-related complications and an important cause of reduced quality of life and disability. Our results support the use of semaglutide in this patient group."
