SGLT-2 inhibitors: pharmacokinetics characteristics and effects on lipids

ABSTRACT

Introduction: Type 2 diabetes mellitus is characterized by increased cardiovascular morbidity and mortality. Atherogenic dyslipidemia is common in this population, consisting of the triad of increased triglycerides, increased small dense low-density lipoprotein (LDL) particles and decreased high-density lipoprotein cholesterol (HDL-C) levels, leading to increased cardiovascular risk.

Areas covered: Aim of the review is the presentation of pharmacokinetic characteristics of the currently available sodium-glucose cotransporters 2 (SGLT-2) inhibitors and the effects of these drugs on lipid metabolism. SGLT-2 inhibitors share a common favorable pharmacokinetic profile, are orally administered with long half-lives (allowing for a once daily dosing) and have been proven to be effective in reducing blood glucose levels. However, the SGLT-1 inhibitory capacity differs between these drugs, an effect that may affect their antidiabetic and cardiovascular effects. SGLT-2 inhibitors alter serum lipids modestly in a similar manner. Specifically, an increase of total cholesterol, LDL cholesterol, and HDL-C levels as well as a decrease of triglycerides concentration is observed. Additionally, the administration of these agents may reduce the atherogenic small dense LDL particle levels, an effect that could provide additional cardiovascular protection in the long term.

Expert opinion: The effect of SGLT-2 inhibitors on diabetic dyslipidemia may be one of their cardioprotective mechanisms.

KEYWORDS:

• SGLT-2
• pharmacokinetics
• bioavailability
• lipids
• cholesterol
• triglycerides
• cardiovascular

Article highlights

• Currently approved sodium-glucose cotransporters 2 (SGLT-2) inhibitors are orally administered once-daily and excreted through both the feces and the kidneys.

• Empagliflozin has the highest SGLT-2 receptors affinity, whereas canagliflozin has the highest affinity for SGLT-1 receptors compared with the other drugs.

• Diabetic dyslipidemia, characterized by the triad of increased serum triglycerides, decreased serum high-density lipoprotein cholesterol (HDL-C), and predominance of the atherogenic small dense low-density lipoprotein (LDL) particles is commonly found in individuals with diabetes mellitus.

• SGLT-2 inhibitors administration results in a small increase in both LDL-C and HDL-C levels and a small decrease in triglycerides concentration.

• The small increase in LDL-C concentration is combined with a reduction of the atherogenic small dense LDL particles, an effect that may play a role in cardiovascular risk reduction.

• Thus, SGLT-2 inhibitors modestly improve all factors of diabetic dyslipidemia (triglycerides, HDL-C, small dense LDL particles) possibly contributing to a reduction of residual cardiovascular risk.

This box summarizes key points contained in the article.

Declaration of interest

T Filippatos has given lectures for Bristol-Myers Squibb, Pfizer, Lilly, Abbott, Amgen, AstraZeneca, Novartis, Vianex, Teva, and MSD. V Tsimihodimos has given lectures for Angelini, Astra-Zeneca, Boehringer-Ingelheim, Lilly, NovarEs, Novo Nordisk, Elpen, Sanofi, Servier, Vianex-MSD and has received an unrestricted research grant from Astra-Zeneca. M Elisaf has given lectures for Astra-Zeneca, has received grants for research protocols and has given lectures for MSD, has given lectures for Pfizer, AbboA, Sanofi-AvenEs, Boehringer Ingelheim, EliLilly and GSK. The authors have no other 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 apart from those disclosed.

Reviewer disclosures

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

Additional information

Funding

This paper was not funded.