Currently metabolic and bariatric surgery remains the gold standard for treatment of morbid obesity and T2DM

However there will be a lot of new possible drug therapies in the future

• Below are some examples that are on trial at the moment
• They are not available yet probably for several years

Orforglipron Is an oral GLP-1 receptor agonist (instead of Saxendra or Ozempic injection)   This is in a phase 2 trial at the moment with reported: 8.6 – 12.6% body weight loss (at 26 weeks) 9.4 – 14/7% (at 36 weeks) Weight reduction of at least 10% by 36 weeks in 46 – 75% of patients But 10 – 17% develop GIT side effects

CagriSema Is a combination GLP-1RA Semaglutide 2.4mg with long acting amylin analogue cagrilintide 2.4mg   This is in a phase 2 RCT at the moment CagriSema has better improvement in glycaemic control (HbA1C) compare to cagrilintide alone CagriSema resulted in better weight loss compare to cagrilintide and Semgalutide alone

Dual action medications   Survodutide Is a dual (glucagon and GLP-1 receptor) incretin agonist   Survodutide is in a phase 2 RCT at the moment Survodutide produced greater body weight loss than the Semaglutide group and better HbA1C levels at 16 weeks amongst the T2DM patients     AMG-133 Amgen Is a novel dual action bispecific glucose dependent insulinotrophic polypeptide receptor (GIPR) antagonist plus GLP-1RA   There is a report of 7.2 to 14.5% weight loss by 85 days

Triple action medications Retatrutide Is a triple action GIFR, GLP-1 and glucagon receptor agonist   New England Journal of Medicine 2023 Retatrutide is in a phase 2 trial which reported: Weight reduction of 17.5% (at 24 weeks) and 24.2% (at 48 weeks)

Bimagrumab This is not for weight loss but it is worth mentioning here Is an antibody that blocks activin type 2 receptors and stimulate skeletal muscle growth   This is in a phase 2 trial at the moment which reported: Significant loss of fat mass, gain in lean muscle mass and metabolic improvements in patients with obesity or T2DM during the 48 weeks of treatment

Summary Currently (in 2024) the only GLP-1 injections available are Ozempic, Wegovy or Saxendra The GLP-RA injections are better for patients with a lower BMI or as adjunct after bariatric and metabolic surgery The injections may help lose 10-20% total body weight but they are usually prescribed for 12 months and maybe longer periods of time *They can be more expensive in the long term *Patients may regain weight after they stopped the injections The GLP-1RA injections may have side effects and some patients can’t tolerate the injection They need to be ceased for about 1 month before elective gastroscopy or surgery to reduce the anaesthetic risk, especially aspiration The bariatric metabolic surgery is more suitable for patients with BMI over 40 especially patients with high blood pressure, diabetes, sleep apnoea, other health issuesand They may help lose >30% total body weight Surgery has better weight loss result, is more durable and more cost effective But obviously surgery have intra-operative and post operative risk and complications