Undesirable effects and persistence of gliflozine treatment in patients with type 2 diabetes mellitus

OBJECTIVE OF THE STUDY SIDECAR (SGLT2-Inhibitors in Diabetes: Evaluation of metabolic Control and Adverse events in the Real-world), is a monocentric prospective observational study performed to monitoring in clinical practice patients with type 2 diabetes (T2D) treated with SGLT2-i to evaluate metabolic and anthropometric evolution during time, as well as the onset of adverse effects (AEs). Design and methods. Demographic features, T2D duration, and clinical parameters at baseline have been recorded as mean ± Standard Deviation (SD) for continuous variables, and frequency distribution for discrete variables. A repeated measures regression model was utilized for the evolution during time of parameters. AEs prevalence were recorded with stratification for main clinical and demographic features at baseline. RESULTS N=220 patients, with 18 months available follow-up, treated with SGLT2-i (N= 19 canagliflozin, 8.6%; N=91 dapagliflozin, 41.4%; N=110 empagliflozin, 50%) monotherapy or in combination according to AIFA indications). Really effective was the action of SGLT2-i on glucose metabolism, with rapid reduction in HbA1c and fasting plasma glucose after 6 months, as well as after 12 and 18 months (HbA1c: -1,0%; fasting plasma glucose: -34,8mg/dL). Weight and BMI showed a satisfying improvement, while waist circumference was statistically significant only after 12 months. Blood pressure, total cholesterol, and renal function were not modified by the treatment. But, apart from the valuable effects on metabolic parameters, 86 patients (39%) suspended SGLT2-i treatment mainly because ineffectiveness (15,7%) or for Genito-Urinary Tract Infections (GUTIs) appearance (14,3%). CONCLUSIONS Median term follow-up confirms the efficacy of SGLT2-i, but a significant percentage of patients is forced to suspend these drugs especially for GUTIs appearance. Such high prevalence of non-serious AEs limits the potential nephro-cardiovascular benefits related to SGLT2-i utilization. A possible chance to reduce GUTIs should come from single tablet association of SGLT2-i and DPP4-i actually available on the market. KEY WORDS type 2 diabetes; SGLT2 inhibitors; genito-urinary tract infections; real world evaluation; health education

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Effectiveness and Safety of SGLT2 Inhibitors in Clinical Routine Treatment of Patients with Diabetes Mellitus Type 2

Journal of Clinical Medicine ◽

10.3390/jcm10040571 ◽

2021 ◽

Vol 10 (4) ◽

pp. 571

Author(s):

Maximilian Hopf ◽

Christof Kloos ◽

Gunter Wolf ◽

Ulrich Alfons Müller ◽

Nicolle Müller

Keyword(s):

Blood Pressure ◽

Urinary Tract ◽

Systolic Blood Pressure ◽

Urinary Tract Infections ◽

Sglt2 Inhibitors ◽

Clinical Routine ◽

Patients With Diabetes ◽

Tract Infections

The aim of this study was to investigate the effectiveness of SGLT2 inhibitors with regard to metabolic parameters and patient safety under routine ambulatory conditions. Retrospective longitudinal study of 95 patients with type 2 diabetes (diabetes duration 13.3 y; HbA1c 8.9%; eGFR 80.1 mL/min) receiving SGLT-2-inhibitors. Metabolic control and adverse event profile were evaluated. The mean follow-up time was 1.2 ± 0.8 years. The following changes were observed: HbA1c −1.0% ± 1.9 (p < 0.001), eGFR −7.0 mL/min ± 13.3 (p < 0.001), albuminuria −23.9 mg/g creatinine ± 144.5 (p = 0.118), bodyweight −3.0 kg ± 5.8 (p < 0.001), systolic blood pressure −6 mmHg ± 22 (p = 0.01), diastolic blood pressure −2 mmHg ± 14 (p = 0.243). 53 participants continuously applied the therapy. Twenty-eight participants discontinued SGLT-2-inhibitors due to various reasons: 20 participants because of genital- or urinary tract infections. One for dysuria, seven due to reduced eGFR below 45 mL/min. This study showed a considerable reduction of HbA1c and a modest reduction of eGFR, bodyweight and systolic blood pressure under clinical routine conditions. Genital infections occurred markedly more often than in randomized controlled trials. To apply SGLT-2-inhibitors more safely in clinical routine individual risks for genital and urinary tract infections should be considered and re-evaluated during therapy.

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Prevalence, risk factors and microorganisms of urinary tract infections in patients with type 2 diabetes mellitus: a retrospective study in China

Therapeutics and Clinical Risk Management ◽

10.2147/tcrm.s147078 ◽

2018 ◽

Vol Volume 14 ◽

pp. 403-408 ◽

Cited By ~ 4

Author(s):

Ke He ◽

Yun Hu ◽

Jun-Cheng Shi ◽

Yun-Qing Zhu ◽

Xiao-Ming Mao

Keyword(s):

Diabetes Mellitus ◽

Risk Factors ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Retrospective Study ◽

Urinary Tract ◽

Urinary Tract Infections ◽

Tract Infections

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

Oncotarget ◽

10.18632/oncotarget.21126 ◽

2017 ◽

Vol 8 (59) ◽

pp. 100678-100690 ◽

Cited By ~ 9

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

Revista da Associação Médica Brasileira ◽

10.1590/1806-9282.65.2.246 ◽

2019 ◽

Vol 65 (2) ◽

pp. 246-252 ◽

Cited By ~ 2

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.

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PDB4 Characterization of the Risk for Urinary Tract Infections in US Patients with Type 2 Diabetes Mellitus

Value in Health ◽

10.1016/j.jval.2011.08.1307 ◽

2011 ◽

Vol 14 (7) ◽

pp. A472

Author(s):

K. Lento ◽

Y. Qiu ◽

A.Z. Fu ◽

S.S. Engel ◽

R. Shankar ◽

...

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Urinary Tract ◽

Urinary Tract Infections ◽

Tract Infections

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A clinical prediction rule for urinary tract infections in patients with type 2 diabetes mellitus in primary care

Epidemiology and Infection ◽

10.1017/s0950268808001015 ◽

2008 ◽

Vol 137 (2) ◽

pp. 166-172 ◽

Cited By ~ 3

Author(s):

L. M. A. J. VENMANS ◽

K. J. GORTER ◽

G. E. H. M. RUTTEN ◽

F. G. SCHELLEVIS ◽

A. I. M. HOEPELMAN ◽

...

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Urinary Tract ◽

Urinary Tract Infections ◽

Prediction Rule ◽

Clinical Prediction Rule ◽

Receiver Operating Curve ◽

Tract Infections

SUMMARYWe aimed to develop a prediction rule for urinary tract infections (UTIs) in patients with type 2 diabetes mellitus (DM2). A 12-month prospective cohort study was conducted in patients with DM2 aged ⩾45 years to predict the occurrence of recurrent UTIs in women and lower UTIs in men. Predictors for recurrent UTI in women (n=81, 2%) and lower UTIs in men (n=93, 3%) were age, number of general practitioner (GP) visits, urinary incontinence, cerebrovascular disease or dementia. In women, renal disease was an additional predictor. The optimum corrected area under the receiver-operating curve (AUC) was 0·79 (95% CI 0·74–0·83) for women and 0·75 (95% CI 0·70–0·80) for men. Using a cut-off score of 4, women with a lower risk assignment had a probability of 0·3% for the outcome. For a cut-off score of 6, women with a higher risk assignment had a probability of 5·8%. For men these figures were 0·8 and 7·1 for a cut-off score of 2 and 4, respectively. Simple variables can be used for the risk stratification of patients.

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

Therapeutic Advances in Drug Safety ◽

10.1177/2042098621997703 ◽

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.

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