An update of SGLT1 and SGLT2 inhibitors in early phase diabetes-type 2 clinical trials

Abstract

Introduction: More than 424 million adults have diabetes mellitus (DM). This number is expected to increase to 626 million by 2045. The majority (90-95%) of people with DM has type 2-diabetes (T2DM). The continued prevalence of DM and associated complications has prompted investigators to find new therapies. One of the most recent additions to the antidiabetic armamentarium are inhibitors of sodium-glucose co-transporters 1 and 2 (SGLT1, SGLT2). Areas covered: The authors review the status of SGLT2 inhibitors for the treatment of T2DM and place an emphasis on those agents in early phase clinical trials. Data and information were retrieved from American Diabetes Association, Diabetes UK, ClinicalTrials.gov, PubMed, and Scopus websites. The keywords used in the search were T2DM, SGLT1, SGLT2 and clinical trials. Expert opinion: The benefits of SGLT inhibitors include reductions in serum glycated haemoglobin (HbA1c), body weight, blood pressure and cardiovascular and renal events. However, SGLT inhibitors increase the risk of genitourinary tract infections, diabetic ketoacidosis and bone fractures. The development of SGLT inhibitors with fewer side effects and as combination therapies are the key to maximizing the therapeutic effects of this important class of anti-diabetic drug.

Tackling type 2 diabetes-associated cardiovascular and renal comorbidities: a key challenge for drug development

“…liraglutide, exenatide, albiglutide) [30,31], and the newly approved SGLT inhibitors (e.g. canagliflozin, dapagliflozin, empagliflozin) [32].…”

“…Many clinical trials have reported that SGLT2i either alone or with GLP-1RA has a potent cardioprotective effect and safety even in DM patients with previous CVD [32,59]. Large clinical trials including the CREDENCE clearly showed the benefit of SGLT2i in the amelioration of cardiovascular risks in diabetic patients [60].…”

“…In contrast to other hypoglycemic agents, GLP-1RA and SGLT2i can reduce major cardiovascular events, and renal morbidities in T2DM patients even in those with existing cardiorenal diseases [32,54,59].…”

“…GLP-1RA such as exenatide delay gastric emptying and decrease the blood level of glucagon, stimulate insulin release and insulin sensitivity, increase satiety, and eventually reduce body weight [70]. On the other hand, SGLT2i prevents the reuptake of glucose from renal convoluted tubules resulting in lower blood glucose and body weight [32] In the light of the analysis of different hypoglycemic agents, which one(s) of them would be most suitable for the treatment of T2DM in patients with cardiorenal comorbidities? In my opinion, the agents that would fit into this 'safe' agent include GLP-1RA and SGLT2i.…”

Editorial: Autophagy and Related Transcription Factors in Liver and Gut Diseases

“…In another interesting review article, Kanasaki et al analyzes distinct molecular mechanisms of autophagy regulation by glucagon, GLP-1, and DPP-4 inhibitor. In addition, they also discuss the potential contribution of these regulatory pathways in the induction of beneficial autophagy-upon bariatric surgery, which have implications in the treatment of diabetic diseases (Adeghate et al, 2019).…”