How does treatment of Diabetes change once kidney disease has developed

How does treatment of Diabetes change once kidney disease has developed?

As significant Chronic Kidney Disease develops, treatment of DM becomes complicated due to many factors. Chronic Kidney Disease is associated with increased insulin resistance.

At the same time the kidneys are responsible for one-third of exogenous insulin degradation. In addition, the kidneys play a role in the metabolism and excretion of many of the oral antidiabetic medications.

With all of these factors contributing, it is difficult to estimate what a patient will need. Close monitoring is recommended to ensure ongoing good glycemic control. The following treatments have special considerations in the setting of DKD.

Metformin

A first-line therapy for diabetics, metformin was originally contraindicated for patients with kidney disease.

However, the U.S. Food and Drug Administration (FDA) has amended this exclusion and now advises to continue giving metformin in patients with an eGFR greater than 30 to 45 mL/min per 1.73 m ² if already on the therapy.

If a patient currently taking metformin has a drop in eGFR less than 45 mL/min per 1.73 m ² , the risks of possible lactic acidosis must be compared with the benefit of glycemic control in that particular patient.

Glucagon-like Peptide-1 (GLP-1) Receptor Agonists and Dipeptidyl Peptidase 4 (DPP-4) Inhibitors

GLP-1 agonists were first isolated from the saliva of the Gila monster. GLP-1 agonists are classified as incretins secondary to their ability to promote insulin and inhibit glucagon secretion.

Likewise, DPP-4 inhibitors inhibit glucagon. Due to side effects of nausea and vomiting, as well as increasing sodium excretion in the urine, there are numerous case reports of kidney failure due to volume depletion associated with these drugs. However, early studies suggested a possible nephroprotective effect with these agents.

This is supported by findings from the Liraglutide Effect and Action in Diabetes (LEADER) study that examined the GLP-1 agonist liraglutide. This study of almost 10,000 patients demonstrated in prespecified secondary outcomes reduced the composite of new-onset persistent macroalbuminuria, persistent doubling of serum creatinine, ESKD, or death from kidney disease compared with usual care. There is limited evidence in using these agents in individuals with severe kidney disease with an eGFR of less than 30 mL/min per 1.73 m ² .

Sodium-Glucose Cotransporter-2 (SGLT-2 ) Inhibitors

The use of SGLT-2 inhibitors in patients with diabetes has shown improvements in mortality and cardiovascular events. Early studies suggest that they may slow the progression of DKD by decreasing hyperfiltration and by decreasing the inflammatory and fibrotic response to hyperglycemia.

Canagliflozin’s kidney outcomes were not considered significant, but it did reduce the composite of a 40% drop in eGFR, need for dialysis, or death from kidney disease (hazard ratio [HR] 0.6, 95% confidence interval [CI] 0.47 to 0.77). Its applicability for use in patients with DKD is still under study, and there are ongoing clinical trials assessing SGLT-2 inhibitors’ ability to treat DKD as a primary outcome.

Currently these agents are contraindicated with an eGFR less than 30 mL/min per 1.73 m ² and are not recommended to be initiated at an eGFR of less than 60 mL/min per 1.73 m ² .