Semaglutide, which belongs to the class of drugs called glucagon-like peptide-1 (GLP-1) receptor agonists, was originally developed for and is also used to treat type 2 diabetes. However, its effects on weight loss have led researchers to study its effect on weight loss in people living with obesity.
It is currently not approved for obesity anywhere in the world, however new drug applications are under review by the US Food and Drug Administration (FDA), the European Medicines Agency (EMA), and other health agencies globally.
The STEP trials published over the past year have established the efficacy and safety of semaglutide in treating patients with obesity.
Here are some of the semaglutide studies being presented at this year’s ECO:
Semaglutide causes similar weight loss across different age groups
Session AD12.01, Thursday 13 May, 1500-1507H, Room 1
In this study, an additional study of the STEP1 trial, change in body weight (%) was greater for semaglutide than for placebo and was consistent across age groups: 40 years and under mean weight loss 15.2% semaglutide group versus 2.3% placebo; 40-60 years 14.6kg semaglutide versus 2.5kg placebo; and 60 years and over 14.7kg semaglutide versus 2.4kg placebo. The changes in lean:fat mass ratio were found to be more pronounced in those patients under 50 years – the authors suggest the metabolic effects of ageing could be behind this difference.
The safety of semaglutide was generally consistent across age groups. Gastrointestinal disorders were the most commonly reported adverse events across all age groups.
The authors conclude: “In this new analysis of the STEP 1 trial, weight loss with once-weekly semaglutide 2.4 mg was achieved consistently across different age groups. There was no evidence of differences in treatment effect by weight loss and body composition across age groups for semaglutide or placebo. Treatment with semaglutide reduced percentage body fat mass and increased percentage lean body mass in all subjects, which was more pronounced in those aged under 50 years. Semaglutide was generally well tolerated with an adverse event profile consistent with the known class effects of this drug – glucagon-like peptide-1 receptor agonists (GLP-1) – irrespective of age.”
Contact the authors: Dr Dror Dicker, Hasharon Hospital-Rabin Medical Center and Tel Aviv University, Tel Aviv, Israel. E) daniel3@013.net
For original STEP 1 trial published in NEJM, please click here
For full abstract, click here
Twitter: #ECO2021 @EASOobesity
Semaglutide reduces body weight regardless of patient characteristics, but females and those with lower body weight have better results
Poster EP4-50
The original STEP 1 study included 1,961 randomised participants (mean age 46 years, body weight 105.3 kg, BMI 37.9 kg/m²; 74.1% female). For categorical weight loss, the observed proportions of participants with ≥20%, 15–<20%, 10–<15% and 5–<10% weight loss at week 68 were 34.8%, 19.9%, 20.0% and 17.6% with semaglutide vs 2.0%, 3.0%, 6.8% and 21.2% with placebo, respectively.
The distribution of participants across weight-loss groups did not appear to be affected by any baseline characteristics, except sex and baseline body weight. Mean percent weight loss at week 68 with semaglutide was greater among females (–18.4%) than males (–12.9%), and in participants with lower vs higher baseline body weight (–18.6% for participants with <90 kg body weight at baseline; –13.9% for participants with ≥115 kg baseline body weight).
The authors conclude: “We found that weight loss with once-weekly injections of semaglutide 2.4 mg was seen in all subgroups evaluated and was generally not influenced by baseline characteristics. The exceptions were sex and baseline body weight; female sex and a low baseline body weight were associated with a slightly greater response to semaglutide. These data support the use of semaglutide 2.4 mg across a broad population of patients with overweight or obesity.”
Contact the author team: Professor Robert Kushner, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA. E) rkushner@northwestern.edu
For full abstract, click here
For small slide presentation provided by the authors, click here
Semaglutide suppresses appetite, food cravings and energy intake
Poster EP4-64
In total, 72 subjects were randomised (44 males, mean age 42.8 years, BMI 34.4 kg/m²); 70 completed this study. There was no evidence of delayed gastric emptying at week 20, as assessed indirectly via paracetamol absorption. Mean energy intake during the ad libitum lunch test meal at week 20 was 35% lower with semaglutide 2.4 mg vs placebo (1736 vs 2676 kJ); estimated treatment difference 940 kJ, both statistically significant findings.
The overall appetite score showed significant reduction in appetite with semaglutide 2.4 mg vs placebo; individual appetite components showed significant reductions in ‘hunger’ and ‘prospective food consumption’ and increases for ‘fullness’ and ‘satiety’. In general, the authors recorded fewer and weaker food cravings, notably reduced cravings for savoury foods and better control of eating with semaglutide 2.4 mg vs placebo. All results detailed here were statistically significant. No new safety signals were seen.
The authors conclude: “In subjects with obesity, semaglutide 2.4 mg suppressed appetite and reduced the frequency and strength of food cravings. Energy intake during a lunch at week 20 in which participants were free to eat as much as they wanted was 35% lower with semaglutide 2.4 mg vs placebo. There was also no clinically relevant effect on gastric emptying with semaglutide 2.4 mg at steady state, measured by paracetamol uptake.”
They add: “Control of appetite and reduced frequency and strength of food cravings are important for weight management in people living in obesity, especially in a society which promotes unhealthy lifestyles and overeating.”
Contact the authors: Dr Dorthe Skovgaard, Novo Nordisk A/S (the manufacturer of the drug), Søborg, Denmark. E) dcsk@novonordisk.com
The research has recently been published in the journal Diabetes, Obesity and Metabolism.
For full poster, click here
For full paper for your readers, please click here
New experimental drug cagrilintide (AM833), when combined with semaglutide, shows potential for treatment of obesity (The Lancet)
Session AD12.04, Thursday 13 May, 1421-1428H, Room 1
An early study of a new experimental drug to treat obesity known as cagrilintide shows that, when combined with semaglutide 2.4 mg, the combination leads to more weight loss than semaglutide 2.4 mg alone and is well tolerated. This phase 1 study, which was recently published in The Lancet will be presented at this year’s ECO by Dr Lone Enebo, Novo Nordisk A/S, Denmark, on behalf of her colleagues. Novo Nordisk A/S is the manufacturer of both drugs in this study.
The authors conclude: “Treatment with cagrilinitide at all tested doses in combination with semaglutide 2.4 mg was generally well tolerated with an acceptable safety profile. The data support once-weekly dosing. The combination of cagrilintide 1.2, 2.4, or 4.5 mg + semaglutide 2.4 mg led to greater weight loss compared with semaglutide 2.4 mg only.”
They add: “As our data support the further clinical development of this drug combination for weight management, a phase 3 trial programme is now being planned to test cagrilinitide in combination with semaglutide for weight management.”
Contact the author team: Dr Lone Enebo, Novo Nordisk A/S, Søborg, Denmark. TE) lobe@novonordisk.com
This study was recently published by The Lancet on April 22, 2021
For full article, click here
For full linked commentary, click here
Another study on cagrilintide is also being presented at this congress. Click here for abstract
Contact for this study: Professor Rachel Batterham, University College London, UK. E) r.batterham@ucl.ac.uk