Part Three | Next generation obesity therapies

Part three of our series of articles looking into anti-obesity treatments brings us to the most recent developments that look set to frame the landscape of future therapies. Here we’ll examine anti-obesity drugs in phase II and phase III trials and some of the combination therapies which have offered hope for new avenues of treatment in the global obesity epidemic.

What does the future hold for the development of GLP-1 antagonists and the ongoing relationship between pharmacotherapy and anti-obesity? Obesity, Type 2 diabetes, and cardiovascular disease: Finding the magic bullet.

Anti-obesity drugs currently in phase III trials

Ozempic (semaglutide) is a GLP-1 agonist, delivered subcutaneously and currently in phase III trials for obesity, although it has already been approved for the treatment of type 2 diabetes.

In phase II data presented in 2018, adults with obesity who were treated with semaglutide 0.4 mg administered by once-daily injections lost between 6% and 13.8% of their body weight after 52 weeks of treatment, significantly more than those treated with placebo who lost 2.3% of their body weight [Ref 1].

In August 2017, Ozempic showed superiority in weight loss and HbA1_c over Trulicity (dulaglutide). Ozempic is a once weekly drug so it remains to be seen if these advantages carry over to this regimen. Novo Nordisk plans to initiate a phase III program (STEP) with once-weekly subcutaneous semaglutide in obesity; as well as a cardiovascular outcome trial called SELECT. Novo Nordisk is also developing an oral form of semaglutide and analysts expect this drug to reach the market by around 2022.

In December 2018, Saniona announced statistically and clinically significant weight loss for its serotonin–noradrenaline–dopamine reuptake inhibitor NS 2330 (tesofensine) (now Tesomet) in its phase III Viking study for treating obesity. The study found a 10% average weight loss in 24 weeks and showed that more than half of patients lost more than 10% in weight. In general, tesofensine was very well tolerated with low incidence of adverse events. Further studies are underway.

New treatment for Prader Willi Syndrome and Hypothalmic Obesity?

Saniona also has Tesomet in a Phase II trial to treat Hypothalmic Obesity (a rare disease characterized by a constant craving for food with severe consequences for the patients) and for Prader Willi Syndrome.

Combination drugs can also offer new avenues for benefit

The 2017 phase II study of Invokana (canagliflozin) from Janssen Pharma, plus phentermine, showed the combination provided statistically superior weight loss versus placebo at week 26 (-6.9%). It also provided statistically superior achievement of weight loss of at least 5% and reduction in systolic blood pressure [Ref 2].

These recent clinical trials show promise of a changing treatment landscape for obesity. Without doubt, obesity is one of the most widespread and pressing medical conditions that faces the world today. The relentless growth in the prevalence of obesity over the last few decades has brought with it a wide range of clinical, social and economic problems that are estimated to have cost the world economy $2tn in 2012 alone. According to the Centers for Disease Control and Prevention, obesity has more than quadrupled in adolescents over the past three decades, over a third of children and adolescents in the US are now overweight or obese.

Join us next time, where we’ll be looking at the further development of GLP-1 antagonists and the ongoing relationship between pharmacotherapy and anti-obesity.

See part 1 here: The effects of obesity and the links to diabetes and cardiovascular disease – now and in the future.

See part 2 here: New hopes for treatment in the global obesity epidemic.

See part 4 here: Obesity, Type 2 diabetes and cardiovascular disease: Finding the magic bullet.

Ref 1. Efficacy and safety of semaglutide compared with liraglutide and placebo for weight loss in patients with obesity: a randomised, double-blind, placebo and active controlled, dose-ranging, phase 2 trial. O'Neil PM et al. The Lancet 2018 Aug 25;392(10148):637-649. doi: 10.1016/S0140-6736(18)31773-2.
Ref 2. Coadministration of Canagliflozin and Phentermine for Weight Management in Overweight and Obese Individuals Without Diabetes: A Randomized Clinical Trial. Hollander P et al. Diabetes Care. 2017 May;40(5):632-639. doi: 10.2337/dc16-2427.