Review of glucagon‐like peptide‐1 receptor agonists for the treatment of type 2 diabetes mellitus in patients with chronic kidney disease and their renal effects

Type 2 diabetes mellitus (T2DM) is the most common cause of chronic kidney disease (CKD), and when it causes CKD it is collectively referred to as diabetic kidney disease. One of the newer therapies for managing hyperglycemia is the glucagon‐like peptide‐1 receptor agonist (GLP‐1RA) drug class. This review summarizes the effects of GLP‐1RAs in patients with T2DM with CKD and evidence for renoprotection with GLP‐1RAs using data from observational studies, prospective clinical trials, post hoc analyses, and meta‐analyses. Evidence from some preclinical studies was also reviewed. Taken together, subgroup analyses of patients with varying degrees of renal function demonstrated that glycemic control with GLP‐1RAs was not markedly less effective in patients with mild or moderate renal impairment vs that in patients with normal function. GLP‐1RAs were associated with improvements in some cardiorenal risk factors, including systolic blood pressure and body weight. Furthermore, several large cardiovascular outcome studies showed reduced risks of composite renal outcomes, mostly driven by a reduction in macroalbuminuria, suggesting potential renoprotective effects of GLP‐1RAs. In conclusion, GLP‐1RAs effectively reduced hyperglycemia in patients with mild or moderately impaired kidney function in the limited number of studies to date. GLP‐1RAs may be considered in combination with other glucose‐lowering medications because of their ability to lower glucose in a glucose‐dependent manner, lowering their risk for hypoglycemia, while improving some cardiorenal risk factors. Potential renoprotective effects of GLP‐1RAs, and their renal mechanisms of action, warrant further investigation.     

Hypoglycemia in diabetes: The dark side of diabetes treatment. A patient‐centered review

Hypoglycemia is a frequent occurrence in patients with diabetes who are treated with insulin and insulin secretagogues. Hypoglycemia is the limiting factor that prevents patients from achieving the glycemic control known to reduce the microvascular complications of diabetes. Recurrent episodes of hypoglycemia can lead to impaired awareness of hypoglycemia where the first symptom of a low blood sugar is unconsciousness. The fear of hypoglycemia has a significant effect on the quality of life of patients and their families. In the acute setting, hypoglycemia can kill, and clinical trials have demonstrated that a single episode of severe hypoglycemia increases the risk of subsequent mortality and cardiovascular events. Clinicians must make efforts to recognize and prevent hypoglycemia in order to prevent the adverse events associated with this event. Patient education is central to these efforts. Recent developments in glucose monitoring and drug development have provided more approaches that can be used to reduce the risk of hypoglycemia in patients with diabetes.