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 anti-diabetic 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 hemoglobin (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.

Trial registration: ClinicalTrials.gov identifier: NCT01986881.

KEYWORDS:

• SGLT1
• SGLT2 inhibitors
• type 2 diabetes mellitus
• clinical trials

Article Highlights

• Diabetes mellitus currently affects 424 million people globally.

• Short and long-term complications of diabetes mellitus (DM) are still common in spite of the large pool of medications available to treat the disease.

• SGLT1 and 2 inhibitors block the reabsorption of glucose from the intestinal mucosa and proximal convoluted tubules, respectively.

• SGLT1 and 2 inhibitors cause significant reductions in body weight, blood pressure, and HbA1c level.

• SGLT2-induced reduction in cardiovascular and renal events in T2DM patients with well-established CVD and kidney disease, is an added advantage for this class of hypoglycemic agents.

• Dual SGLT inhibitors with fewer side effects have great potential to succeed as a major addition to the anti-diabetic drugs armamentarium.

This box summarizes key points contained in the article.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

The research of the authors is funded by College of Medicine and Health Sciences, United Arab Emirates University 31M374.