Abstract

Diabetes mellitus (DM) is associated with dreadful changes in the cardiovascular and renal systems, causing increased morbidity and mortality. Sodium-glucose cotransport-2 (SGLT2) inhibitors belong to the oral hypoglycemic group of drugs believed to reduce these events by various mechanisms in DM. We performed a systematic review to determine the effectiveness of SGLT2 inhibitors in reducing cardiovascular and renal complications and address safety concerns in participants with type 2 diabetes mellitus (T2DM).We explored PubMed, PubMed Central, Medical Literature Analysis and Retrieval System Online (MEDLINE), Cochrane library, and ResearchGate for randomized controlled trials and observational studies done on the advantages of SGLT2 inhibitors in the prevention or reduction of worsening cardiovascular and renal changes in T2DM. Studies were screened for the quality assessment using the Cochrane risk-of-bias assessment tool and Newcastle-Ottawa scale. We screened 5615 articles, out of which 22 articles with 7,02,977 diabetes mellitus patients treated with SGLT2 inhibitors were used for the systematic review after meticulously filtering articles based on inclusion and exclusion criteria. The trials included one of the following drugs - empagliflozin, dapagliflozin, canagliflozin, and luseogliflozin. SGLT2 inhibitors significantly reduced the risk of heart failure (HF), frequency of hospitalizations due to HF, all-cause mortality, cardiovascular mortality, and nonfatal myocardial infarction. Renal outcomes showed a significant lowering of risk of acute kidney failure, progression of chronic kidney disease, renal mortality, and improvement in urinary albumin creatinine ratio. We noticed an initial worsening of the estimated glomerular filtration rate followed by stabilizing and reaching the baseline on long-term treatment, especially in end-stage renal failure patients.The review showed that SGLT2 inhibitors have adverse reactions similar to that of a placebo, with a slight increase in treatable genital mycotic and urinary tract infections but no evidence of diabetic ketoacidosis, fractures, and amputations. According to the available data, SGLT2 inhibitors can significantly prevent or reduce cardiovascular diseases and kidney abnormalities in patients with type 2 diabetes mellitus with tolerable safety outcomes.

Highlights

  • BackgroundCentre for Disease Control and Prevention (CDC) data states that as of 2018, diabetes mellitus (DM) in the USA is prevalent in approximately 10.5% of the population, with serious microvascular and macrovascular complications [1]

  • According to American Diabetes Association (ADA), these drugs are currently recommended as supplement treatment in type 2 diabetes mellitus (T2DM) patients with high risk or established Cardiovascular disease (CVD), established chronic kidney disease (CKD), or heart failure (HF) independent of hemoglobin A1C (HbA1C) values of

  • This systematic review is performed to consolidate the evidence of sodium-glucose cotransport-2 (SGLT2) inhibitors to reduce cardiovascular and renal complications and adverse effects in diabetes mellitus from 22 randomized control trials and observational studies

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Summary

Introduction

The other beneficial effect of SGLT2 inhibitors is their promotion of sodium excretion in urine that causes osmotic diuresis and reduced blood pressure [4,5]. These drugs reduce endogenous glycerol-derived hepatic gluconeogenesis from visceral adipose tissue causing weight loss [6]. One of the renal protective mechanisms of SGLT2 inhibitors is in albuminuria where it reduces intraglomerular pressure and prevents subsequent tubular cell injury [7]. These pleiotropic effects have reduced cardiovascular events and preserved kidney functions. According to American Diabetes Association (ADA), these drugs are currently recommended as supplement treatment in T2DM patients with high risk or established CVD, established CKD, or heart failure (HF) independent of hemoglobin A1C (HbA1C) values of

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