Sodium-glucose co-transporter 2 inhibitors induced euglycemic diabetic ketoacidosis within four days of initiation

Euglycemic diabetic ketoacidosis(EDKA)is a well-known complication of sodium-glucose co-transporter 2 inhibitors,and many cases with variable onset following the initiation of these agents are reported before,with a median onset of approximately 2 wk.This letter discusses a 45-year-old lady who initially presented with ischemic stroke but developed EDKA 4 d after starting empagliflozin,a rare occurrence.The patient had severe metabolic acidosis that necessitated admission into the intensive care unit.Prompt discontinuation of empagliflozin and DKA management resulted in clinical recovery.

Euglycemic diabetic ketoacidosis:A rare but serious side effect of sodium-glucose co-transporter 2 inhibitors

Sodium-glucose co-transporter 2(SGLT2)inhibitors are an insulin-independent class of oral antihyperglycemic medication and from recently established therapy in chronic heart failure patients.A rare,but potentially life-threatening complication of SGLT2 inhibitor use is euglycemic diabetic ketoacidosis.We described a case of a middle-aged male patient with type 2 diabetes who developed metabolic ketoacidosis after a few days of empagliflozin administration.SGLT2 inhibitor related ketoacidosis presents with euglycemia or only modestly elevated glucose blood concentrations,which causes delayed detection and treatment of ketoacidosis.There are multiple possible risk factors and mechanism that might contribute to the pathogenesis of ketoacidosis.It is implied that SGLT2 inhibitor use and prescription by non-diabetologists(cardiologists,nephrologists,family physicians,etc.)will continue to grow in the future.It is important to inform the general cardiac public about this rare but serious side effect of SGLT2 inhibitors.

Novel and emerging diabetes mellitus drug therapies for the type 2 diabetes patient

Type 2 diabetes mellitus is a metabolic disorder of deranged fat, protein and carbohydrate metabolism resulting in hyperglycemia as a result of insulin resistance and inadequate insulin secretion. Although a wide variety of diabetes therapies is available, yet limited efficacy, adverse effects, cost, contraindications, renal dosage adjustments, inflexible dosing schedules and weight gain significantly limit their use. In addition, many patients in the United States fail to meet the therapeutic HbA1c goal of < 7% set by the American Diabetes Association. As such new and emerging diabetes therapies with different mechanisms of action hope to address some of these drawbacks to improve the patient with type 2 diabetes. This article reviews new and emerging classes, including the sodium-glucosecotransporter-2 inhibitors, 11β-Hydroxysteroid dehydrogenase type 1 inhibitors, glycogen phosphorylase inhibitors; protein tyrosine phosphatase 1B inhibitors, G Protein-Coupled receptor agonists and glucokinase activators. These emerging diabetes agents hold the promise of providing benefit of glucose lowering, weight reduction, low hypoglycemia risk, improve insulin sensitivity, pancreatic β cell preservation, and oral formulation availability. However, further studies are needed to evaluate their safety profile, cardiovascular effects, and efficacy durability in order to determine their role in type 2 diabetes management.

Finally, Some Reason for Hope in Proteinuric Kidney Disease

Background: After years of predictable outcomes with limited tools to combat the ravages of proteinuric chronic kidney disease (CKD) associated with or without diabetes, exciting new options are available to slow the progression of CKD. Purpose: Focusing on sodium-glucose co-transporter 2 inhibitors (SGLT2), angiotensin receptor blockers (ARB), angiotensin converting enzyme inhibitors (ACE I), and new mineralocorticoid antagonists (MRA), this review examines how these agents compliment the standard of care in an attempt to educate and stimulate broader use of these agents. Methods: Using the search terms “mineralocorticoid antagonist, sodium glucose co-transporter 2 inhibitors, proteinuria, albuminuria, and diabetic kidney disease,” five randomized controlled clinical trials were identified and then analyzed in the context of the results found from the Irbesartan Diabetic Nephropathy Trial (IDNT). Two trials using SGLT2 and 2 using MRA were reviewed. Results: In the 2 SGLT2 trials renal outcomes were reduced by 30% - 39% among patients with estimated GFR ranging from roughly 25 - 90 mL/min. In the 2 MRA trials, renal outcomes fell by 13% - 18% among patients with estimated GFR ranging from 25 - 90 mL/min. In the IDNT, renal outcomes fell by 19%. Trial duration ranged from 28 - 41 months, and in all trials, the IDNT, Ace inhibitors (ACE I) and ARBs use was uniform. There is small overlap in the 5 trials in which both MRA and SGLT2 agents were used. Conclusions: Over a wide range of renal function, both MRA and SGLT2 inhibitors demonstrate outstanding efficacy in diabetic and non-diabetic (SGLT2) proteinuric kidney disease. Compared to the prior standard of care, these agents dramatically improve outcomes.

Advances in reducing cardiovascular risk in the management of patients with type 2 diabetes mellitus

Treatment intended to lower cardiovascular (CV) risk in patients with diabetes has always been a primary goal of diabetes treatment. Due to the subdued effects of reducing hemoglobin A1c (HbA1c) on macrovascular complications, controlling other CV risk factors such as hypertension and hyperlipidemia instead of hyperglycemia has been the mainstay treatment to improve CV outcome in patients with type 2 diabetes mellitus (T2DM) until recent years. This review is intended to summarize and compare the results from the available cardiovascular outcome trials (CVOTs) for the two classes of glucose lowering drug: sodium-glucose cotransporter 2 inhibitor (SGLT2i) and glucagon-like peptide-1 receptor agonist (GLP-1 RA). The results including the EMPA-REG, CANVAS program and DECLARE-TIMI 58 trials for SGLT2i, and the ELIXA, LEADER, SUSTAIN-6, EXSCEL and HARMONY trials for GLP-1 RA were summarized. The potential mechanisms of these CV beneficial effects and the optimal CV risk reduction treatment in patients with T2DM based on patient risk stratification and evidence from these CVOTs in real-world setting were discussed.