The role of sodium-glucose co-transporter-2 inhibitors in the treatment of type 1 diabetes mellitus
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Abstract
Sodium-glucose co-transporter-2 (SGLT2) inhibitors, also known as gliflozins, are a class of antidiabetic medications that alter the SGLT2 protein found in the nephron of the kidney. The SGLT2 protein is directly responsible for 90% of the glucose reabsorption at the proximal tubule of the nephron. By inhibiting these SGLT2 proteins, gliflozins prevent the kidney reuptake of glucose from the glomerular filtrate and subsequently lower the glucose level in the blood by promoting increased excretion of glucose in the urine. SLGT2 inhibitors have been proven in a myriad of clinical studies to be effective as a second-line therapy for patients struggling with type 2 diabetes mellitus (DM2). There are a number of gliflozins currently approved for use in patients with DM2, and they are commonly prescribed to patients who have additional comorbidities that require control such as hypertension and hyperlipidemia.
Although enough evidence exists for the efficacy of SGLT2 inhibitors in treating and managing symptoms of DM2, there is increased interest into their role in managing glycated hemoglobin levels, otherwise known as HbA1c, in diabetic patients, including those that have type 1 diabetes mellitus (DM1). DM1 is an autoimmune attack on the ß-islet cells of the pancreas that are directly responsible for insulin production. Despite active research, there is currently no cure for DM1, and treatment focuses on managing blood sugar levels with exogenous insulin. Even though exogenous insulin is essential in preventing excessively high blood glucose levels in patients with DM1, these patients often oscillate between hyperglycemic and hypoglycemic conditions, leading to secondary complications such as diabetic ketoacidosis and hypertension.
Therefore, there is a need for adjuvant therapies in addition to exogenous insulin that will help patients with DM1 stay healthy. Recent studies that observed the combined treatment of insulin therapy along with SGLT2 inhibitors for DM1 have shown that SGLT2 inhibitors effectively control blood glucose levels, reduce the overall demand of the body for insulin, and promote weight loss. These drugs have been found to adequately maintain HbA1c levels below 7.0%. However, patients taking SGLT2 inhibitors, regardless of pre-existing condition, are at an increased risk for diabetic ketoacidosis, lower limb amputation, and genital infections. DM1 patients are already at an increased risk for diabetic ketoacidosis because of a lack of endogenous insulin production, forcing the body to shift to ketosis if regular insulin therapy is not administered.
Caution must thus be taken on the part of the prescribing physician when choosing to add an SLGT2 inhibitor to a treatment plan for a patient with DM1. The patient must be aware of the benefits and risks of treatment, comply with the insulin regimen, and adhere to strict follow-up to prevent potential life-threatening side effects that come with this adjuvant therapy.