Obesity and its causes are the focus of extensive research evaluating new therapeutic targets. Get an at-a-glance update on progress and FDA approvals during 2021
Pharmacologic options for obesity management have been limited, but increased understanding of the pathophysiology of the disease of obesity has given rise to promising drug targets and novel therapeutic strategies, according to the authors of a recent review in Endocrine Reviews.
The authors point to a broad range of systems and tissues being investigated as sites of targets for pharmacotherapy including the central nervous system, gastrointestinal hormones, adipose tissue, kidney, liver, and skeletal muscle.
Scroll through the slides below for concise summaries of new obesity drugs under investigation and coming into play in 2021.
FDA-approved medications. Phentermine became the first medication to receive FDA approval for the treatment of obesity in 1959. Others now FDA-approved are diethylpropion, benzphetamine, phendimetrazine, orlistat, phentermine/topiramate ER (Qsymia), bupropion/naltrexone (Contrave), liraglutide (Saxenda), setmelanotide (Imcivree), and semaglutide (Wegovy). Anti-diabetic medications (eg, metformin) often are prescribed for obesity "off label." Harvard Health.
Weight loss with semaglutide. In the phase 3 STEP 1 trial of adults with overweight or obesity, once-weekly subcutaneous semaglutide plus lifestyle intervention was associated with substantial, sustained, clinically relevant mean weight loss of 14.9%. At least 5% weight loss was attained by 86% of participants. Those who received semaglutide had greater improvement in cardiometabolic risk factors and participant-reported physical functioning. New England Journal of Medicine.
Semaglutide gets FDA nod. Semaglutide injection (2.4 mg once weekly) gained FDA approval (June 2021) for chronic weight management in adults with obesity or overweight and at least 1 weight-related condition (eg, high blood pressure) for use in addition to a reduced calorie diet and increased physical activity. The glucagon-like peptide-1 (GLP-1) analogue is the first drug approved for chronic weight management in adults with general obesity or overweight since 2014. FDA
Investigational cagrilintide with semaglutide shows promise. Once-weekly subcutaneous cagrilintide (a long-acting amylin analogue) plus 2.4 mg of semaglutide resulted in significantly greater weight loss than with semaglutide alone in a randomized, placebo-controlled, multiple-ascending dose, phase 1b trial (May 2021). Concomitant treatment with cagrilintide and semaglutide 2.4 mg for weight management was well tolerated with an acceptable safety profile. Lancet
Cagrilintide alone vs liraglutide, placebo. In a phase 2 trial (Nov 2021), once-weekly cagrilintide led to significant reductions in body weight and was well tolerated in persons with overweight and obesity. Mean percentage weight reductions were greater with all doses of cagrilintide vs placebo; weight reductions were greater with cagrilintide 4.5 mg vs liraglutide 3.0 mg (approved for weight loss). The authors suggested that their findings support the development of molecules with novel mechanisms of action for weight management. Lancet.
Developmental diabetes drug tirzepatide also reduces weight. In the phase 3 SURPASS-2 trial (Aug 2021), reductions in baseline hemoglobin A1c and body weight with tirzepatide were significant and superior to those with semaglutide. Tirzepatide, a dual glucose-dependent insulinotropic polypeptide and GLP-1 receptor agonist, is under development for treatment of patients with type 2 diabetes. New England Journal of Medicine.
Bimagrumab blockade trims body mass. In a phase 2 randomized clinical trial (Jan 2021), blockade of activin type II receptors with bimagrumab led to significant loss of total body fat mass, gain in lean mass, and metabolic improvements in patients with overweight or obesity who had T2D. ActRII pathway inhibition may provide a novel approach for pharmacologic management of excess adiposity and accompanying metabolic disturbances. JAMA Network Open.
Setmelanotide OK’d for rare obesity disorders. In November 2020, setmelanotide (a melanocortin-4 receptor agonist) received its first FDA approval for chronic weight management in patients ≥ 6 years with obesity caused by pro-opiomelanocortin, proprotein convertase subtilisin/kexin type 1, or leptin receptor deficiency. This November, the FDA accepted for filing a supplemental New Drug Application for patients with Bardet-Biedl syndrome or Alström syndrome. GlobeNewswire.
Medical device offers alternative to drugs. Oral superabsorbent hydrogel (Plenity), FDA cleared in 2019 as a medical device for treatment of overweight and obesity, provides a nonsystemic, effective alternative as an aid to weight management therapy. In a pivotal clinical trial, mean weight loss was 6.4% in the treatment group vs 4.4% in the placebo group. Unlike currently approved pharmacologic options, Plenity is indicated for patients with a body mass index as low as 25 kg/m2 without comorbidities. It does not have a restriction on duration of therapy. ClinicalDiabetes.