Caution is advised when prescribing SGLT-2 inhibitors to patients with moderately impaired renal function and those at risk for volume depletion and hypotension.
The beneficial effects of SGLT2 inhibitors on various aspects of renal function make them an attractive choice in patients with (and possibly without) diabetes-associated renal impairment.
Of these, only the DPP-4 inhibitor linagliptin can be used across all stages of renal impairment without dosing restrictions or concerns regarding dose escalation, and all SGLT2 inhibitors are contraindicated when eGFR <45 mL/min/1.73m<sup>2</sup>.
SGLT2 inhibition relative to placebo was associated with preservation in serum creatinine levels or initial increases followed by return to baseline levels in patients with renal impairment, but levels were preserved in patients without renal impairment.
Several ongoing dedicated renal outcomes trials will provide further guidance on the potential clinical role of SGLT2 inhibitors in slowing the development and progression of renal impairment in individuals with T2DM.
Ongoing SGLT-2 inhibitor CVOTs will help clarify the potential of these drugs to treat T2D comorbid with different forms of HF (HF with preserved vs reduced ejection fraction) and different degrees of renal dysfunction, and in individuals with T2D vs pre-diabetes or normal glucose metabolism.
The current review article summarises these aspects and discusses possible mechanisms with SGLT2 inhibitors in protecting heart failure and renal dysfunction in diabetic patients.
Traditional management of diabetes mellitus has focused on glycemic control, beginning with lifestyle changes, followed by metformin, and then other classes of antiglycemic agents.<sup>1</sup> Sodium glucose co-transporter 2 (SGLT2) inhibitors reduce cardiovascular (CV) events, including CV death, myocardial infarction (MI) and heart failure, and slow progression of renal dysfunction, including prevention of end-stage kidney disease (ESKD).<sup>2-3</sup> Because initial clinical trials included mostly patients with baseline HbA1c >7%, current guidelines have recommended this class as add-on therapy for patients whose HbA1c is not at goal, typically ≥7%.<sup>1</sup> We hypothesized that there would be similar benefits on CV and renal endpoints regardless of baseline HbA1c, including those with HbA1c <7%.