An update on the safety and efficacy of oral antidiabetic drugs: DPP-4 inhibitors and SGLT-2 inhibitors

ABSTRACT

Introduction: Oral antidiabetic medications are important in many type 2 diabetes care plans

Areas covered: The article summarizes the cardiovascular and renal safety data for DPP-4 inhibitors and SGLT-2 inhibitors and specific safety data particular to each class.

Expert opinion: DPP-4 and SGLT-2 inhibitors provide unique anti-hyperglycemic mechanisms. The cardiovascular safety profiles of DPP-4 inhibitors are promising, but do not show the strong CV risk reduction of empagliflozin and canagliflozin. The heart failure signal associated with DPP-4 inhibitor use is unclear with differing agents, demonstrating increased risk or maybe even protective effects. The risk reduction in cardiovascular disease associated with SGLT-2 inhibitors has translated to recommendations to consider these therapies early in the treatment pathway. Both classes have potential safety concerns that necessitate appropriate patient selection and thorough education on potential side-effects. DPP-4 inhibitors are considered to have neutral or in some studies beneficial renoprotective effects. SGLT-2 inhibitor safety effects on the kidney are more complex. There are reports of acute kidney injury occurring soon after initiating SGLT-2 inhibitor therapy. However, there are large recent studies that have demonstrated the beneficial effect of SGLT-2 inhibitors in slowing the progression of established chronic kidney disease.

Trial registration: ClinicalTrials.gov identifier: NCT01243424.

Trial registration: ClinicalTrials.gov identifier: NCT01897532.

Trial registration: ClinicalTrials.gov identifier: NCT02065791.

Trial registration: ClinicalTrials.gov identifier: NCT01986881.

KEYWORDS:

• SGLT-2 inhibitor
• DPP-4 inhibitor
• cardiovascular risk
• renoprotective risk
• type 2 diabetes

Article highlights

• New guidelines highlight the prioritization of medical therapies associated with reduced major adverse cardiovascular risk or mortality.

• SGLT-2 inhibitors have excellent efficacy and have demonstrated beneficial cardiovascular outcomes in high cardiovascular risk individuals and renal outcomes (in established renal disease).

• DPP-4 inhibitors are modestly effective and have demonstrated neutral cardiovascular benefits with an unclear association of saxagliptin and alogliptin with hospitalization for heart failure. Positive effects on albuminuria have been noted.

• SGLT-2 inhibitor and DPP-4 inhibitor therapy may be limited by cost and availability.

• Oral therapy choices should be individualized based on efficacy and tolerability but also weighing the class-specific potential for adverse outcomes in a specific individual.

This box summarizes the key points contained in the article.

Declaration of interest

The authors report no conflicts of interest.

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.