scholarly journals The risk for urinary tract infections with sodium-glucose cotransporter 2 inhibitors: no longer a cause of concern?

2019 ◽  
Vol 13 (1) ◽  
pp. 24-26 ◽  
Author(s):  
Pantelis A Sarafidis ◽  
Alberto Ortiz
Keyword(s):  
Type 2 Diabetes ◽  
Urinary Tract ◽  
Case Reports ◽  
European Medicines Agency ◽  
Sodium Glucose Cotransporter ◽  
Increased Risk ◽  
The Us ◽  
Post Marketing ◽  
Tract Infections

Abstract Sodium–glucose co-transporter-2 (SGLT2) inhibitors improve cardiovascular and renal outcomes in patients with type 2 diabetes, including those with diabetic kidney disease. However, the US Food and Drug Administration and European Medicines Agency warnings about potential adverse effects, such as urosepsis and pyelonephritis, based on post-marketing case reports, may deter physicians from prescribing these drugs. A recent evaluation of two large US-based databases of commercial claims failed to find evidence for an increased risk of urinary tract infection (UTI) or severe UTI in type 2 diabetes patients who were prescribed an SGLT2.

scholarly journals Use of sodium-glucose cotransporter-2 inhibitors and urinary tract infections in type 2 diabetes patients: a systematic review

2019 ◽  
Vol 65 (2) ◽  
pp. 246-252 ◽  
Author(s):  
Izabela Rodrigues Figueiredo ◽  
Sara Cardoso Paes Rose ◽  
Nathália Bandeira Freire ◽  
Marina Stabile Patrocínio ◽  
Natália Pierdoná ◽  
...  
Keyword(s):  
Systematic Review ◽  
Type 2 Diabetes ◽  
Urinary Tract ◽  
Urinary Tract Infections ◽  
Randomized Clinical Trials ◽  
Oral Antidiabetic Agents ◽  
Sodium Glucose Cotransporter ◽  
Increased Risk ◽  
Tract Infections

SUMMARY Sodium-glucose cotransporter-2 inhibitors (SGLT2i) are drugs that act by maintaining glycosuria. Recent studies have shown promising effects of these in the treatment of type 2 diabetes mellitus (DM2). However, there may be an increased risk of developing urinary tract infections (UTIs) in patients treated with these. Our study aims to analyze the association between the risk of UTI in patients treated with SGLT2i. A systematic review of the literature was carried out by randomized clinical trials, totalizing at the end of the selection 23 articles that were statistically evaluated. The incidence of UTI was generally demonstrated in articles and in different subgroups: patients on SGLT2i monotherapy or on combination therapy; according to specific comorbidities of each sample or according to the drug used. They noticed an increase in the chance of UTI in the SGLT2i groups compared to the control groups on placebo or other oral antidiabetic agents. This increased chance was found predominantly with the use of Dapagliflozin, Canagliflozin, and Tofogliflozin, regardless of the dosing. Lastly, stands out that the dimension of UTI chances for DM2 patients who use SGLT2i remains to be more strictly determined.

scholarly journals Sodium-glucose cotransporter-2 inhibitors and risk for genitourinary infections in older adults with type 2 diabetes

2021 ◽  
Vol 12 ◽  
pp. 204209862199770
Author(s):  
Navya Varshney ◽  
Sarah J. Billups ◽  
Joseph J. Saseen ◽  
Cy W. Fixen
Keyword(s):  
Type 2 Diabetes ◽  
Older Adults ◽  
Urinary Tract ◽  
Real World ◽  
Fungal Infections ◽  
Sodium Glucose Cotransporter ◽  
Increased Risk ◽  
Significant Difference ◽  
Tract Infections

Background and aims: Although landmark clinical trials have demonstrated an increased risk for genitourinary infection (GUI) after initiation of sodium-glucose cotransporter-2 inhibitor (SGLT2i) therapy that led to an FDA label warning, real world findings have been inconsistent and evidence specifically in older adults is lacking. The objective of the study was to examine the incidence of GUI in patients aged 65 years or older initiated on SGLT2i compared with glucagon-like peptide-1 receptor agonist (GLP1-RA) therapy at a large academic health system. Methods: A retrospective population-based cohort study was conducted using electronic health records of patients aged 65 years and older with a diagnosis of type 2 diabetes mellitus. Patients newly initiated on SGLT2i or GLP1-RA therapy with estimated glomerular filtration rate (eGFR) ⩾30 mL/min per 1.73 m² and active within the health system for at least 1 year prior to initiation were included. We compared the incidence of inpatient, emergency room, or outpatient diagnosis of GUI (bacterial and mycotic) within 6 months of SGLT2i or GLP1-RA initiation. A chi-square or Fisher’s exact test were used to analyze between-group differences for categorical variables, while a t-test was used for continuous variables. A Cox proportional hazards model was used to estimate the impact of confounding variables on the primary outcome. Results: One hundred and thirty-three patients were initiated on SGLT2i therapy and 341 patients newly initiated on GLP1-RA therapy. After adjusting for differences in age, A1c, body mass index, eGFR, race and sex, there was no statistically significant difference in GUI incidence within 6 months of SGLT2i versus GLP1-RA initiation (3.8% versus 6.5%, adjusted hazard ratio: 0.784, 95% confidence interval 0.260–2.367). Conclusion: We found no increased risk of composite GUI within 6 months of initiating SGLT2i compared with GLP1-RA therapy. These real-world data in older adults add to previous findings, which suggest no increased risk of urinary tract infection with SGLT2i initiation. Plain language summary A class of antidiabetic medications and risk for genitourinary infections in older adults with type 2 diabetes Older adults with type 2 diabetes often benefit from a class of antidiabetic medications known as sodium-glucose cotransporter-2 inhibitors (SGLT2is) which help to lower blood glucose, decrease risk for cardiovascular disease and prevent kidney disease progression. However, there is concern that these medications may increase risk for urinary tract infections and/or genital fungal infections in older adults based on clinical trial evidence. Our study evaluated the real-world occurrence of these safety events in patients aged 65 years or older who were newly started on these medications. We compared these patients with a group of patients newly started on an alternative class of antidiabetic agents which are not expected to increase risk for infections, known as glucagon-like peptide-1 receptor agonists (GLP1-RA). In our study, we included 133 patients who started an SGLT2i and 341 patients who started a GLP1-RA at a large teaching hospital. We evaluated the occurrence of infection up to 6 months after initiation of these mediations. We found no significant difference in infection rate between these two groups. We conclude in the study that the use of SGLT2i in older adults was not associated with increased risk for urinary tract infections or genital fungal infections when compared with GLP1-RA use.

Euglycemic Diabetic Ketoacidosis Associated With Sodium–Glucose Cotransporter Type 2 Inhibitors in Patients With Type 2 Diabetes Mellitus Receiving Oral Therapy

2017 ◽  
Vol 32 (2) ◽  
pp. 240-243 ◽  
Author(s):  
Ryan B. Dull ◽  
Mikayla L. Spangler ◽  
Emily L. Knezevich ◽  
Britney M. Lau
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Diabetic Ketoacidosis ◽  
Case Reports ◽  
Serious Adverse Events ◽  
Type 2 Dm ◽  
Sodium Glucose Cotransporter ◽  
Increased Risk

Introduction and Objective: Postmarketing reports and warnings of serious adverse events such as diabetic ketoacidosis (DKA) have raised concern regarding the safety of sodium–glucose cotransporter 2 inhibitors (SGLT2i). This report describes 2 cases of symptomatic SGLT2i-associated euglycemic DKA (euDKA) leading to hospitalization in patients with type 2 diabetes mellitus (DM) previously well controlled on oral medications. Case Reports: Subject 1 is a 55-year-old female admitted with euDKA precipitated by infection and managed with intravenous insulin. This case was notable for a delayed diagnosis of euDKA and lack of clinical improvement despite withholding dapagliflozin. Subject 2 is a 62-year-old male admitted with euDKA precipitated by infection. His clinical condition improved rapidly and euDKA responded to withdrawal of empagliflozin alone. Discussion: Applying the Naranjo adverse medication reaction probability scale to each case (subject 1 score = 3 points; subject 2 score = 4 points) suggests these are possible adverse reactions to SGLT2i. Data from randomized controlled trials suggest DKA events in adults with type 2 DM receiving SGLT2i are rare and similar to placebo. However, data from a large cohort suggest these events occur more frequently and are associated with a 2-fold increased risk of DKA. Conclusion: This class of medications may be associated with a higher real-world risk of DKA in adults with type 2 DM than previously reported. Patients prescribed these medications should receive vigilant assessment for features of traditional DKA as well as euDKA.

scholarly journals Urinary tract infections in patients with type 2 diabetes mellitus with pharmacological glucosuria

2020 ◽  
Vol 92 (11) ◽  
pp. 106-109
Author(s):  
N. V. Sturov ◽  
S. V. Popov ◽  
N. K. Mamporia ◽  
A. A. Mager
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Urinary Tract ◽  
Urinary Tract Infections ◽  
Renal Tubules ◽  
Sodium Glucose Cotransporter ◽  
Glucose Reabsorption ◽  
Tract Infections

Selective inhibitors of sodium-glucose cotransporter belong to a new class of drugs for the treatment of type 2 diabetes mellitus. The mechanism of their action is based on insulin-independent reduction of glucose reabsorption in the proximal renal tubules, which leads to stimulation of its excretion in the urine and, accordingly, to a decrease in the concentration of glucose in the blood plasma. Drugs of this group demonstrate effectiveness in the treatment of type 2 diabetes, but their use may be associated with an increased frequency of urinary tract infections. Pharmacological glucosuria, which leads to a decrease in the concentration of glucose in the blood, creates the preconditions for the occurrence of urinary tract infections. Urinary tract and genital infections are the most common adverse events associated with the use of sodium-glucose cotransporter inhibitors. In the presented literature review for 20162019, the relationship between urinary tract infections in patients with type 2 diabetes mellitus and therapy with sodium-glucose cotransporter inhibitors was analyzed.

Evolving Evidence of Diabetic Ketoacidosis in Patients Taking Sodium-Glucose Cotransporter 2 Inhibitors

2020 ◽  
Vol 105 (8) ◽  
pp. 2475-2486 ◽  
Author(s):  
Nicola Fleming ◽  
Peter Shane Hamblin ◽  
David Story ◽  
Elif I Ekinci
Keyword(s):  
Type 2 Diabetes ◽  
Blood Glucose ◽  
Diabetic Ketoacidosis ◽  
Case Reports ◽  
Significant Risk ◽  
Hormonal Changes ◽  
Precipitating Factors ◽  
Sodium Glucose Cotransporter ◽  
Increased Risk

Abstract Introduction Sodium glucose cotransporter 2 inhibitors (SGLT2i) have emerged as an important class of blood glucose–lowering medications, due to cardiovascular, metabolic, and renal benefits. However, there is a small but significant risk of diabetic ketoacidosis (DKA) associated with their use. Methods A literature search was conducted in Ovid MEDLINE and Embase to July 2019 using variants on the key search terms sodium-glucose cotransporter 2, diabetic ketoacidosis, and type 2 diabetes. A broad spectrum of evidence was incorporated to facilitate a comprehensive narrative review. Further sources were identified through hand searching of reference lists. Discussion Although cardiovascular outcome trials demonstrated mixed evidence of SGLT2i associated DKA, increasing evidence from case reports and cohort studies has identified an increased risk. SGLT2i use is associated with a ketotic state caused by an increased glucagon:insulin ratio and stimulated by factors including stress-induced hormonal changes, insufficient insulin, decreased glucose, increased ketone resorption, and hypovolemia. Atypical presentations of DKA with lower-than-expected blood glucose levels are possible with SGLT2i use, so clinical and biochemical monitoring is vital for early identification and management. DKA risk is particularly increased with precipitating factors, therefore optimization of risk factors is vital. Recommendations for perioperative and sick day management of patients taking SGLT2i have been suggested based on available evidence. Conclusion SGLT2i are an excellent class of drug in the physician’s toolkit for managing type 2 diabetes. However, both clinicians and patients must be aware of the potential for DKA and the need for increased monitoring, both clinically and biochemically, when potential precipitating factors are present. In acutely unwell patients, these medications should be withheld to reduce the risk of DKA.

scholarly journals Treatment of Heart Failure with Sodium-Glucose Cotransporter 2 Inhibitors and Other Anti-diabetic Drugs

2019 ◽  
Vol 5 (1) ◽  
pp. 27-30 ◽  
Author(s):  
Thomas A Zelniker ◽  
Eugene Braunwald
Keyword(s):  
Heart Failure ◽  
Type 2 Diabetes ◽  
Renal Failure ◽  
Cardiovascular Death ◽  
Cardiovascular Outcomes ◽  
Sodium Glucose Cotransporter ◽  
Increased Risk ◽  
Patients With Diabetes ◽  
Glucagon Like Peptide 1

Patients with type 2 diabetes are at increased risk of developing heart failure, cardiovascular death and renal failure. The recent results of three large sodium-glucose cotransporter 2 inhibitor cardiovascular outcomes trials have demonstrated a reduction in heart failure hospitalisation and progressive renal failure. One trial also showed a fall in cardiovascular and total death. A broad spectrum of patients with diabetes benefit from these salutary effects in cardiac and renal function and so these trials have important implications for the management of patients with type 2 diabetes. Selected glucagon-like peptide 1 receptor agonists have also been shown to reduce adverse cardiovascular outcomes.

scholarly journals Characterization of the urinary microbiota of elderly women and the effects of type 2 diabetes and urinary tract infections on the microbiota

Oncotarget ◽  
2017 ◽  
Vol 8 (59) ◽  
pp. 100678-100690 ◽  
Author(s):  
Fengping Liu ◽  
Zongxin Ling ◽  
Yonghong Xiao ◽  
Qing Yang ◽  
Li Zheng ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Urinary Tract ◽  
Urinary Tract Infections ◽  
Elderly Women ◽  
Urinary Microbiota ◽  
Tract Infections
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