Potential Place of SGLT2 Inhibitors in Treatment Paradigms for type 2 Diabetes Mellitus |
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| Affiliation: | 1. Department of Neurosurgery, Tokushima Prefectural Miyoshi Hospital, Japan;2. Department of Neurosurgery, The University of Tokushima Graduate School, Japan;1. From the UCLA David Geffen School of Medicine, Los Angeles, California.;2. Department of Biomathematics; UCLA David Geffen School of Medicine, Los Angeles, California.;3. Section of Endocrine Surgery; UCLA David Geffen School of Medicine, Los Angeles, California.;4. Division of Hematology/Oncology; UCLA David Geffen School of Medicine, Los Angeles, California.;5. Department of Pathology and Laboratory Medicine; UCLA David Geffen School of Medicine, Los Angeles, California.;6. Division of Endocrinology; VA Greater Los Angeles Healthcare System, Los Angeles, California.;7. Division of Endocrinology, Diabetes, and Hypertension; UCLA David Geffen School of Medicine, Los Angeles, California. |
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| Abstract: | Objective: Following the first Food and Drug Administration (FDA) approval in 2013, sodium glucose cotransporter 2 (SGLT2) inhibitors have generated much interest among physicians treating patients with type 2 diabetes mellitus (T2DM). Here, the role in treatment with this drug class is considered in the context of T2DM treatment paradigms.Methods: The clinical trials for the SGLT2 inhibitors are examined with a focus on canagliflozin, dapagliflozin, and empagliflozin.Results: Evidence from clinical trials in patients with T2DM supports the use of SGLT2 inhibitors either as monotherapy or in addition to other glucose-lowering treatments as adjuncts to diet and exercise, and we have gained significant clinical experience in a relatively short time.Conclusion: The drugs appear to be useful in a variety of T2DM populations, contingent primarily on renal function. Most obviously, SGLT2 inhibitors appear to be well suited for patients with potential for hypoglycemia or weight gain. In clinical trials, patients treated with SGLT2 inhibitors have experienced moderate weight loss and a low risk of hypoglycemic events except when used in combination with an insulin secretagogue. In addition, SGLT2 inhibitors have been shown to reduce blood pressure, so they may be beneficial in patients with T2DM complicated by hypertension. SGLT2 inhibitors were incorporated into the 2015 American Diabetes Association (ADA)/European Association for the Study of Diabetes (EASD) position statement on the management of hyperglycemia and received an even more prominent position in the American Association of Clinical Endocrinologists (AACE)/American College of Endocrinology (ACE) comprehensive diabetes management guidelines and algorithm.Abbreviations: AE = adverse event A1C = glycated hemoglobin CI = confidence interval CKD = chronic kidney disease DKA = diabetic ketoacidosis DPP-4 = dipeptidyl peptidase 4 eGFR = estimated glomerular filtration rate FDA = Food and Drug Administration FPG = fasting plasma glucose GLP-1 = glucagon-like peptide 1 HDL-C = high-density lipoprotein cholesterol HR = hazard ratio LADA = late-onset autoimmune diabetes of adulthood LDL-C = low-density lipoprotein cholesterol MACE = major adverse cardiovascular events SGLT1 = sodium glucose cotransporter 1 SGLT2 = sodium glucose cotransporter 2 T1DM = type 1 diabetes mellitus T2DM = type 2 diabetes mellitus UACR = urine albumin to creatinine ratio |
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