TYPE 2 DIABETES, CHRONIC KIDNEY DISEASE, AND GLP-1’S

As I have said many times in past articles, Diabetes Mellitus is a multi-system disease. By that I mean, despite most people thinking the problem with diabetes is just high blood sugar, in reality, diabetes also involves the kidneys, the heart and blood vessels, the eyes, and the nervous systems, both central and peripheral ie. multiple organ systems of the body. The underlying abnormality, though, is an inflammatory process that “attacks” the blood vessels in each of the organ systems involved in diabetes causing a “vasculitis” which slowly damages the organ. 

Ninety percent of patients with diabetes have Type II Diabetes due to insulin resistance, meaning they have acquired a gene that makes their system produce antibodies against their own insulin. These antibodies block the effect of insulin making control of the blood sugar difficult causing blood glucose levels to run abnormally high. Treatment focuses on lowering blood sugar to a level as near normal as possible. 

The treatment of diabetes has changed significantly since the introduction of GLP-1 receptor agonists. Treatment has always included lifestyle changes ie. diet, exercise, weight loss, and what for years was the introductory drug in the treatment regimen, metformin. But metformin has largely been replaced by GLP-1’s, the “wonder drugs” of the 21st century, because of the multiple benefits these drugs have shown. 

Because of their popularity with the public, and the profound beneficial effects they have on people with obesity, diabetes, and chronic kidney disease, Glucagon-Like Peptide-1Receptor Agonists (GLP-1’s) have been the subject of numerous clinical investigations. The Cochrane Library, an independent network of researchers, professionals, patients, and caregivers, who collaborate to promote trusted high quality health information, has recently published their synopsis of 42 studies on GLP-1’s. Their summations are evidence-based and results are rated with Low, Moderate, or High certainty, meaning the results/recommendations are of low, moderate, or high reliability. 

The 42 studies evaluated the effects and risks of GLP-1’s compared with placebo in adults with Type II diabetes and chronic kidney disease. 48,148 patients were studied. The studies had varying lengths of follow-up, and whether it was 26 weeks, 137 weeks, or 200 weeks, GLP-1’s were shown with “moderate certainty” to decrease the risk of major cardiovascular events (cardiovascular death, nonfatal heart attack, nonfatal stroke, and need for coronary bypass surgery) compared with placebo.** To take the perspective of a negative result, there was “low certainty” evidence that GLP-1’s had “little or no effect on cardiovascular death…. compared with placebo.” So when they looked for evidence the drugs didn’t help, they weren’t able to find any. 

Bottom Line: There is fairly reliable evidence that GLP-1’s reduce the risk of major cardiovascular events in patients with diabetes and chronic kidney disease. The adverse gastrointestinal events GLP-1’s cause may affect these results, but are dose dependent and may not be a problem. The article specifically states, however, that “using GLP-1 receptor agonists for people with CKD and diabetes” causes “no harm.”

Dr. G’s Opinion: GLP-1’S are all they say they are, and more. They cause significant weight loss, control diabetes, and improve chronic kidney disease. Now, we also know that GLP-1’s lower the risk of major cardiovascular events. These drugs can be used with impunity because studies have shown they are safe to use and should be used in Type 2 diabetics with CKD.

CKD — Chronic Kidney Disease

Reference: Elliott J, Frasca J. Glucagon-Like Peptide-1 Receptor Agonists for People with Chronic Kidney Disease and Diabetes. Am Fam Phys 2025 October;112(4):369-370.

**ADDENDUM:

Moderate Certainty Evidence:

 1. At 26 weeks, GLP-1’s decreased all-cause death compared with placebo

 2. Over 200 weeks, GLP-1’s decreased cardiovascular death, non-fatal heart attacks, non-fatal

     stroke, and need for hospitalization, or coronary bypass for unstable angina or heart failure

     compared with placebo.

 3. At 137 weeks, GLP-1’s decreased cardiovascular death, non-fatal heart attacks, and non-

     fatal stroke compared with placebo.

 4. There was little of no difference between GLP-1’s and placebo on progression to kidney

     failure.

Low Certainty Evidence:

 1. GLP-1’s had little or no effect on cardiovascular death or severe hypoglycemia compared

     with placebo.