In general, obesity more greatly contributes to the global burden of disease (also associated with co-morbidities) in recent years . For instance, there are type 2 diabetes mellitus (T2DM), hypertension, cardiovascular disease and some cancers. Scientists reported that 39% of adults were overweight and 13% were obese globally in 2016. The main treatments for obesity include lifestyle intervention, pharmacotherapy and bariatric surgery.
Especially, the use of pharmacotherapy in combination with lifestyle intervention (diet and exercise) is recommended for long-term weight management in obese patients. Reflecting the unmet medical need for new treatments for obesity, FDA and other health authorities have approved four new drugs since 2012, including lorcaserin, liraglutide, phentermine HCl/topiramate extended-release and naltrexone HCl/bupropion HCl. And Liraglutide and naltrexone/bupropion have been approved by the heath authority in the European Union (EMEA).
SGLT2 inhibitors have been developed as antidiabetes drugs and lead to a reduction in HbA1c of up to 1%. Under physiological conditions, most filtered glucose (80%-90%) is reabsorbed by SGLT2 in the proximal convoluted tubule of the kidney, while the remainder (10%-20%) is reabsorbed by SGLT1 in the S2/S3 segment.
Liraglutide is a full agonist of the GLP-1 receptor and shares 97% of its amino acid sequence identity with human GLP-1.
However, Liraglutide binds reversibly to serum albumin, and thus has increased resistance to enzymatic degradation and a longer half-life. Also, in preclinical studies, Liraglutide demonstrated good glycaemic control, mediated by the glucose-dependent stimulation of insulin and suppression of glucagon secretion and by delayed gastric emptying. Liraglutide also has positive effects on body weight, beta-cell preservation and mass, and cardiac function.
Moreover, Licogliflozin demonstrates reduced liver fat and serum ALT levels. Licogliflozin (LIK066) is a non-anti-fibrotic treatment agent for non-alcoholic steatohepatitis (NASH).
Yan-Ling He, et al. The effects of licogliflozin, a dual SGLT1/2 inhibitor, on body weight in obese patients with or without diabetes. Diabetes Obes Metab. 2019 Jun;21(6):1311-1321.
L B Knudsen, et al. Liraglutide: the therapeutic promise from animal models. Int J Clin Pract Suppl. 2010 Oct;(167):4-11.