Use Of SGLT2 Inhibitors Research Articles

Identifying Barriers to SGLT2 Inhibitor Use in Patients with CKD: A Qualitative Analysis

Identifying Barriers to SGLT2 Inhibitor Use in Patients with CKD: A Qualitative Analysis

Dapagliflozin-associated euglycemic diabetic ketoacidosis in 66-year-old with type 2 Diabetes: A clinical case report

Euglycemic diabetic ketoacidosis (EDKA) is a rare but serious complication of type 2 diabetes, often associated with the use of SGLT2 inhibitors. This case report describes an episode of EDKA in a 66-year-old male with a long history of type 2 diabetes and multiple comorbidities, who developed this complication following the introduction of dapagliflozin. Although his blood glucose levels remained within normal limits, laboratory tests revealed elevated ketonemia and severe metabolic acidosis. The patient was successfully treated with intravenous hydration and insulin therapy, leading to a rapid improvement in his clinical condition. This case underscores the importance of clinical vigilance and patient education for those treated with SGLT2 inhibitors to prevent and effectively manage this potentially life-threatening complication.

Relationship between SGLT2 inhibitor use and specific cancer types: a systematic review and meta-analysis.

Aim: The study aimed to explore the incidence of cancer as an adverse event to SGLT2 inhibitors (SGLT2i) use in Type 2 diabetes.Materials & methods: The study followed PRISMA guidelines to pool RCTs conforming the inclusion criteria. Random effects model was used to pool risk ratios.Results & conclusion: After reviewing 19 studies, the analysis suggested a possible increased risk of reproductive, breast, thyroid, hematologic/lymphatic, urinary, skin and skeletal cancers with SGLT2i use. Conversely, lower incidences of respiratory and cardiovascular cancers were noted. However, these associations lacked statistical significance. Caution is advised in using SGLT2i due to potential cancer risks, especially in diabetic patients prone to cancer. More RCTs are essential due to limited research in this area.

Effects of the Non-Steroidal MRA Finerenone with and without Concomitant SGLT2 Inhibitor Use in Heart Failure.

Patients with heart failure (HF) with mildly reduced or preserved ejection fraction face heightened long-term risks of morbidity and mortality. The sodium glucose-co-transporter-2 inhibitors (SGLT2i) and the non-steroidal mineralocorticoid receptor antagonist (MRA) finerenone have both been shown to reduce the risk of cardiovascular events in this population, but the effects of their combined use are not known. FINEARTS-HF was a randomized, double-blind, placebo-controlled trial of finerenone in patients with HF and left ventricular ejection fraction (LVEF) ≥40%. Baseline SGLT2i use was a prespecified subgroup. The primary outcome was a composite of total (first and recurrent) worsening HF events and cardiovascular death. We first assessed for evidence of treatment heterogeneity based on baseline SGLT2i use. We further examined SGLT2i uptake during the trial and evaluated the treatment effects of finerenone accounting for baseline and during trial use of SGLT2i in time-varying analyses. Among 6,001 participants, 817 (13.6%) were treated with an SGLT2i at baseline. During 2.6-years median follow-up, treatment with finerenone similarly reduced the risk of the primary outcome in participants treated with an SGLT2i (rate ratio 0.83; 95% confidence interval 0.60 to 1.16) and without an SGLT2i at baseline (rate ratio 0.85; 95% confidence interval 0.74 to 0.98); Pinteraction=0.76. In follow-up, 980 participants initiated SGLT2i, which was less frequent in the finerenone arm compared with placebo (17.7% vs. 20.1%; hazard ratio 0.86; confidence interval 0.76 to 0.97). Time-updated analyses accounting for baseline and subsequent use of SGLT2i did not meaningfully alter the treatment effects of finerenone on the primary endpoint. The treatment benefits of the non-steroidal MRA finerenone were observed irrespective of concomitant use of an SGLT2i. These data suggest that the combined use of SGLT2i and a non-steroidal MRA may provide additive protection against cardiovascular events in patients with HF with mildly reduced or preserved ejection fraction.

Effect of SGLT2 inhibitors on kidney function of type 2 diabetes patients during Ramadan: A systematic review.

SGLT2 inhibitors are known for their osmotic diuretic effect, and their use by Muslim patients with type 2 diabetes during the fasting month of Ramadan may pose an increased risk of volume depletion, potentially impacting renal function. We conducted a systematic review registered on PROSPERO (registration number CRD42020204582) of studies published between 2013 and January 2023, sourced from PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials. The study selection criteria included controlled studies that reported the use of SGLT2 inhibitors (SGLT2i) by fasting adult type 2 diabetes patients and provided data on creatinine or estimated glomerular filtration rate (eGFR) as outcomes. Two prospective observational studies, encompassing a total of 359 participants, of which 197 utilized SGLT2 inhibitors, were identified. Our findings indicated that the use of SGLT2 inhibitors during Ramadan did not result in a significant alteration in eGFR. In one study by Hassanein et al., the mean changes in eGFR for the SGLT2i group, as compared to the non-SGLT2i group, were -1.2 ± 19.4 and 3.1 ± 14.8, respectively (p = 0.06). In a study by Shao et al., the least squares mean changes for eGFR in the SGLT2i group, compared to the non-SGLT2i group, were -6.0 ± 1.5 (95% CI, -8.9 to -3.1) and -4.2 ± 1.6 (95% CI, -7.3 to -1.1), respectively (p = 0.39). Despite the limited number of observational studies available, our analysis suggests that the use of SGLT2 inhibitors by type 2 diabetes patients during Ramadan does not appear to significantly impact kidney function.

Efficacy of Sodium-Glucose 2 Transporter Inhibitors in Heart Failure With Preserved Ejection Fraction: A Narrative Review.

Heart failure with preserved ejection fraction (HFpEF) is an increasingly prevalent condition. It occurs more commonly in older patient populations with multiple comorbidities, such as hypertension, diabetes, and obesity. However, managing HFpEF has been challenging due to its complex pathophysiology, and medications effective for heart failure with reduced ejection fraction (HFrEF) have not shown similar efficacy in HFpEF. Sodium-glucose 2 transporter (SGLT2) inhibitors were originally developed for the treatment of type 2 diabetes mellitus, yet several trials and papers have proved their significant role in HFpEF. Through a variety of mechanisms, including natriuresis, diuresis, and anti-inflammatory effects, to name a few, this class of drugs has shown promising results in HFpEF patients. The use of SGLT2 inhibitors in HFpEF has resulted in improvements in several aspects, including biomarkers, imaging, symptomatology, and mortality. Moreover, SGLT2 inhibitors have a favorable safety profile, which is especially significant given the high comorbidity burden in HFpEF patients. This feature is particularly notable given the type of patient being managed. Extensive research is still being undertaken for their use in HFpEF, given the positive results obtained thus far.

Causality analysis of myopathy secondary to dapagliflozin therapy in type II Diabetes – A case study

Diabetes mellitus is a chronic metabolic condition that is becoming more prevalent globally. Diabetic patients must maintain adequate glycemic control in order to avoid or postpone diabetic complications. Diabetes care has evolved since the introduction of sodium-glucose co-transporter 2 inhibitors (SGLT2i). Postmarketing surveillance has shown cases of diabetic ketoacidosis and increased bone fracture risk associated with the use of SGLT2 inhibitors. We present a case of a 55-year-old female with a 6-year history of diabetes who exhibited weakness, muscular pains, and a burning feeling in her left thigh as a result of Dapagliflozin. Before initiating dapagliflozin treatment, the patient's fasting blood sugar (FBS) was 314 mg/dl and postprandial blood sugar (PPBS) was 343 mg/dl. After adding dapagliflozin as part of the therapy, the FBS improved to 179.24 mg/dl, and the PPBS decreased to 214.39 mg/dl, indicating a significant reduction in blood glucose levels. The introduction of Dapagliflozin in the treatment reduces the therapeutic gap compared to earlier treatment schedule, but retain the same side effect and became rechallenge. The instance of myopathy linked to dapagliflozin was confirmed following the causality evaluation by WHO Schales. It exemplifies the need for detecting drug-induced myopathy. Recently, minimal evidence has emerged showing a link between prolonged SGLT2 inhibitor use and accelerated myopathy. Myopathy is the generalised loss of skeletal muscle mass and function that occurs with ageing. Its existence is linked to negative health outcomes such as physical impairment, low quality of life, and death. Clinically, no other cause of myopathy was detected, and biochemical analysis indicated that dapagliflozin was the cause of her myopathy.

Adverse cardiovascular and kidney outcomes in people with SARS-CoV-2 treated with SGLT2 inhibitors

BackgroundWhether use of SGLT2 inhibitors reduces the risk of cardiovascular and kidney events in people who contracted SARS-CoV-2 infection is not clear.MethodsWe used the healthcare databases of the United States Department of Veterans Affairs to build a cohort of 107,776 participants on antihyperglycemic therapy and had SARS-CoV-2 infection between March 01, 2020 and June 10, 2023. Within them, 11,588 used SGLT2 inhibitors and 96,188 used other antihyperglycemics. We examined the risks of major adverse cardiovascular events (MACE)—a composite of death, myocardial infarction and stroke, and major adverse kidney events (MAKE)—a composite of death, eGFR decline > 50%, and end stage kidney disease after balancing baseline characteristics between groups through inverse probability weighting. Survival analyses were conducted to generate hazard ratio (HR) and absolute risk reduction per 100 person-years (ARR).ResultsOver a median follow up of 1.57 (IQR: 1.05–2.49) years, compared to the control group, SGLT2 inhibitors use is associated with reduced risk of MACE (HR 0.82 (0.77, 0.88), ARR 1.73 (1.21, 2.25)) and reduced risk of MAKE (HR 0.75 (0.71, 0.80), ARR 2.62 (2.13, 3.11)). Compared to the control group, SGLT2 inhibitors use is associated with reduced risk of the secondary outcomes of hospitalization (HR 0.94 (0.90, 0.98), ARR 1.06 (1.36, 1.76)), anemia (HR 0.71 (0.65, 0.76), ARR 2.43 (1.95, 2.90)), and acute kidney injury (HR 0.84 (0.79, 0.89), ARR 1.86 (1.29, 2.42)).ConclusionsAmong people with SARS-CoV-2 infection on antihyperglycemic therapy, compared to those on other antihyperglycemics, those on SGLT2 inhibitors have less risk of adverse cardiovascular and kidney outcomes.

Use of SGLT-2 Inhibitors in Adults (Age ≥ 65) with Type 2 Diabetes and Cardiovascular Disease is Lower in Alberta and Manitoba than in Ontario (2018-2020): A Cross-Sectional Study of Different Drug Funding Policies

ObjectivesSodium-glucose cotransporter 2 inhibitors (SGLT2i) provide heart and kidney benefit in adults with diabetes and cardiovascular disease (CVD). Public drug coverage policies for SGLT2i differ by province in Canada. Our study aimed to describe the potential effects of prior authorization / step therapy (PA/ST) and relatively high income-based deductibles, compared to regular benefit status with modest co-pay, on SGLT2i prescriptions in high-risk adults. MethodsCross-sectional study of individuals age ≥ 65 years with type 2 diabetes and CVD, taking ≥ 1 antihyperglycemic agent from 2019 to 2020, using electronic medical record data from primary care practices. We compared SGLT2i use (2019-2020) in Alberta (PA/ST, modest co-pay), and Manitoba (PA/ST, relatively high income-based deductible), to Ontario (regular benefit status, modest co-pay). Poisson regression was used to adjust for confounders, including age, sex, glycated hemoglobin, and other medication use. Other diabetes medications were estimated as control cases. ResultsWe included 3,191 adults (average age 75 years, 31% female). SGLT2i use was lowest in Manitoba (15.6%), then Alberta (25.9%), and highest in Ontario (31.9%). After adjustment, compared to Ontario, SGLT2i prescriptions were lower in Alberta (prevalence ratio [PR] 0.80, 95% CI [0.71-0.91], p < 0.001) and Manitoba (PR 0.48 [0.39-0.59], p < 0.001). ConclusionsPA/ST and relatively high deductibles are associated with reduced SGLT2i prescribing – PA/ST by approximately 20% in Alberta and Manitoba, and relatively high deductibles by an additional relative reduction of 40% in Manitoba. PA/ST and cost-sharing policies should be flexible and responsive to changing evidence of clinical benefit.

Effect of frailty on effectiveness and safety of GLP-1 receptor agonists versus SGLT2 inhibitors in people with type 2 diabetes in Taiwan: a retrospective, nationwide, longitudinal study

GLP-1 receptor agonists and SGLT2 inhibitors are increasingly being used in people with type 2diabetes on the basis of findings from randomised clinical trials; however, little is known of whether clinical outcomes are affected by frailty in real-world settings. We aimed to compare the clinical effectiveness and safety of GLP-1 receptor agonists and SGLT2 inhibitors in managing type 2diabetes, with a specific focus on stratifying people by their frailty status. In this retrospective, nationwide, longitudinal study, we identified people (aged ≥20years) with type 2 diabeteswho newly initiated either a GLP-1 receptor agonist or an SGLT2 inhibitor during the period Jan 1, 2017to Dec 31, 2019 from the Taiwan National Health Insurance database. Individuals were excluded if they had been diagnosed with cancer, received dialysis for kidney failure, or had prescriptions for a GLP-1 receptor agonist or an SGLT2 inhibitor, within 1year before the index date. Mortality data were collected from the Taiwan National DeathRegistry. Eligible individuals were categorised into three frailty subgroups-fit, mild frailty, and moderate or severe frailty-on the basis of the multimorbidity frailty index. Propensity score matching (1:1) was used to balance covariates between recipients of GLP-1 receptor agonists and SGLT2 inhibitors among each frailty subgroup. Clinical outcomes of interest included three-point major adverse cardiovascular events (non-fatal acute myocardial infarction, non-fatal stroke, and fatal cardiovascular disease), all-cause mortality, hospitalisation for heart failure, dialysis or renal transplant, severe diabetic foot complications, retinopathy, hospitalisation for severe hyperglycaemia, and hospitalisation for severe hypoglycaemia. The association between the use of a GLP-1 receptor agonist versus an SGLT2 inhibitor and the risk of the outcomes of interest among each frailty subgroup was examined using a subdistribution hazard model. We identified 320 210people with type 2diabetes, of whom 280 163 met the eligibility criteria, who initiated either a GLP-1 receptor agonist (n=22 968; mean age 57·7years [SD 13·9], 11 338 [49·4%] were female, and 11 630 [50·6%] were male) or SGLT2 inhibitor (n=257 195; mean age 58·8years [12·3], 107 988 [42·0%] were female, and 149 207 [58·0%] were male) during 2017-19. After matching, 11 882, 7210, and 3414pairs of GLP-1 receptor agonist and SGLT2 inhibitor users were assigned in the fit, mild frailty, and moderate or severe frailty subgroups. All clinical outcomes were comparable between users of GLP-1 receptor agonists and SGLT2 inhibitors among each frailty subgroup, except fora higher risk of hospitalisation for severe hyperglycaemia with GLP-1 receptor agonists than withSGLT2 inhibitors in the mild frailty subgroup (subdistribution hazard ratio 1·25 [95% CI 1·13-1·38]; p<0·0001) and a higher risk of dialysis or renal transplant with GLP-1 receptor agonists than with SGLT2 inhibitors in the fit (2·43 [1·82-3·23]; p<0·0001), mild frailty (3·93 [3·03-5·09]; p<0·0001), and moderate or severe frailty (2·60 [2·03-3·31]; p<0·0001) subgroups. Formulating clear and updated guidelines on the use of GLP-1 receptor agonists and SGLT2 inhibitors according to frailty status could improve management of type 2diabetes. Ministry of Education, Taiwan.

Role of SGLT2 inhibitors in improving cardiac functions (on Echocardiography) in patients having Diabetes Mellitus and ischemic heart disease

BACKGROUND &amp; OBJECTIVE: Sodium-glucose cotransporter-2 inhibitors (SGLT2i or SGLT2 inhibitors) have a distinctive mechanism of action unrelated to insulin secretion or action. By causing glucosuria, they reduce plasma glucose by inhibiting SGLT2 in the proximal tubules of the kidneys. This mechanism of action corrects several metabolic abnormalities, which are, in fact, CVD risks in addition to normoglycemia. This study was conducted to assess the average change in ejection fraction resulting from the use of SGLT2 inhibitors in enhancing cardiac function in patients with Diabetes Mellitus and ischemic heart disease. METHODOLOGY: This is a descriptive case series conducted from 10th December 2022 to 9th May 2023 in the Department of Medicine, Faisalabad Medical University; 435 type II diabetes mellitus patients were selected, according to inclusion and exclusion criteria. All received a daily dose of 20 mg of SGLT2 for three months. Echocardiography was done before and after the treatment period left ventricular ejection fraction (EF) was evaluated, and improvement in cardiac function was noted. RESULTS: In this study, the mean age of participants was 46.54±8.52 years. 314 (72.18%), or the majority, were between 30 and 50. The male-to-female ratio was 1.1:1, with 228 (52.41%) men and 207 (47.59%) women. The mean ejection fraction at baseline was 53.45 ± 4.12. The mean change in ejection fraction of SGLT2 inhibitors in improving cardiac functions among patients having Diabetes Mellitus and ischemic heart disease was 50.79 ± 3.76.( p-value ≤0.001). CONCLUSION: SGLT2 inhibitors effectively improve cardiac functions among patients with Diabetes Mellitus type II and ischemic heart insult

Trajectory of Irisin as a Predictor of Kidney-Related Outcomes in Patients with Asymptomatic Heart Failure.

The purpose of the study is to elucidate whether irisin is a promising predictive biomarker for kidney-related events in patients with T2DM and concomitant asymptomatic HF. We prospectively enrolled 146 T2DM patients who had either evidence of structural cardiac abnormality or elevated levels of N-terminal brain natriuretic pro-peptide (NT-proBNP) > 125 pmol/mL and followed them for 52 weeks. Structural cardiac abnormalities were used as the minimum from the following criteria: abnormal left ventricular (LV) global longitudinal strain (GLS) < -16%, LV hypertrophy, left atrial volume index > 34 mL/m2, abnormal ratio of early transmitral diastolic filling velocity/early mitral annular velocity ≥ 13 units. All the patients underwent echocardiographic and Doppler examinations by two blinded, highly experienced echocardiographers. NT-proBNP, irisin, TNF-alpha, and hs-CRP were quantified in the serum at baseline, at 26 weeks, and at the end of the study. The kidney-related outcomes consisted of an eGFR reduction by 40% from baseline, or end-stage kidney disease, or kidney replacement therapy. We found that levels of irisin at baseline < 4.15 ng/mL and/or its decrease > 20% from baseline in T2DM patients predicted kidney-related events better than baseline levels/dynamic NT-proBNP and the use of SGLT2 inhibitors. In conclusion, we established that a low baseline level of irisin and its 20% decrease correlated with newly kidney-related events in T2DM patients with asymptomatic HFpEF/HFmrEF.

Adropin Predicts Asymptomatic Heart Failure in Patients with Type 2 Diabetes Mellitus Independent of the Levels of Natriuretic Peptides.

In patients with type 2 diabetes mellitus (T2DM), asymptomatic adverse cardiac remodeling plays a pivotal role in the development of heart failure (HF). Patients with T2DM often have low or near-normal levels of natriuretic peptides, including N-terminal brain natriuretic peptide (NT-proBNP), which have been inconclusive in predicting the transition from asymptomatic adverse cardiac remodeling to HF with preserved ejection fraction (HFpEF). The aim of this study was to elucidate the predictive ability of adropin for HFpEF depending on the circulating levels of NT-proBNP. We prospectively enrolled 561 T2DM patients (glycated hemoglobin < 6.9%) with echocardiographic evidence of structural cardiac abnormalities and left ventricular ejection fractions >50%. All patients underwent B-mode transthoracic echocardiographic and Doppler examinations. Circulating biomarkers, i.e., NT-proBNP and adropin, were assessed at baseline. All individuals were divided into two groups according to the presence of low levels (<125 pmol/mL; n = 162) or elevated levels (≥125 pmol/mL; n = 399) of NT-proBNP. Patients with known asymptomatic adverse cardiac remodeling and elevated NT-proBNP were classified as having asymptomatic HFpEF. A multivariate logistic regression showed that low serum levels of adropin (<3.5 ng/mL), its combination with any level of NT-proBNP, and use of SGLT2 inhibitors were independent predictors of HFpEF. However, low levels of adropin significantly increased the predictive ability of NT-proBNP for asymptomatic HFpEF in patients with T2DM, even though the concentrations of NT-proBNP were low, while adropin added discriminatory value to all concentrations of NT-proBNP. In conclusion, low levels of adropin significantly increase the predictive ability of NT-proBNP for asymptomatic HFpEF in patients with T2DM.

Abstract We071: Identifying Preventive and Therapeutic Effects of SGLT2 Inhibitor on Atrial Fibrillation

Background: The frequency and prevalence of atrial fibrillation (AF) and heart failure are expected to increase over time, which are expected to result in enormous medical expenses and socioeconomic losses. Previous studies have confirmed that SGLT2 inhibitor (SGLT2i) reduces cardiovascular mortality and hospitalization rates in heart failure patients. Also, follow-up studies have been reported that the use of SGLT2i reduces atrial fibrillation, and its administration is recommended in clinical practice guidelines. In spite of beneficial effects of SGLT2i on atrial fibrillation, the exact mechanism by which SGLT2i reduces atrial fibrillation has not been revealed. Methods: We performed experiments by creating an AF cell model using Ang II and an AF animal model using Acetylcholin-Calcium chloride. Fibrosis markers and calcium regulatory proteins were confirmed by Western blot, and the occurrence and burden of AF were evaluated by using a 1F catheter in animal models. Results: In our cell studies and animal experiments, the inhibitory effect of SGLT2i administartion on atrial fibrillation was confirmed. First, fibrosis markers tend to reduce in atrial fibrillation models treated with SGLT2i, compared to non-treated atrial fibrillation models. In addition, the phosphorylation of the calcium handling proteins, such as CaMKII, RyR2, and PLB, increased in the AF group, whereas the degree of phosphorylation in SGLT2i treated group decreased to the phosphorylation level in control group. Conclusion: In AF-induced cell and animal models, the effect of SGLT2i was shown to be highly effective against atrial fibrillation. In particular, the results indicate that administration of SGLT2i before inducing atrial fibrillation could bring out the preventive and therapeutic effects through amelioration of fibrosis and reduction of calcium handling proteins phosphorylation.

Amputation Risk in Type II Diabetes Mellitus Patients Treated with SGLT-2 Inhibitors: A Systematic Literature Review of Randomized Clinical Trials.

SGLT-2 inhibitors, prescribed for type 2 diabetes, have a heightened risk of amputation. The FDA issued a warning in May 2017, leading to the inclusion of a cautionary label. Vigilance is essential for patients and healthcare providers to promptly identify and address potential limb complications associated with the use of SGLT-2 inhibitors. A comprehensive search of electronic databases was conducted, covering the period from inception to May 2024. This systematic literature review adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The quality of the included studies was assessed using the Cochrane risk of bias (ROB) tool. Inclusion and exclusion criteria were predefined, and data extraction was performed to summarize the findings. A total of 12 randomized control trial (RCT) studies were included in the present systematic review. 37,657 (54.89%) participants were randomly assigned to receive the different interventions of SGLT-2 inhibitor, whereas 30,959 (45.11%) received a placebo. Overall, 618 events were reported in the treatment group, whereas 396 events were reported in the placebo group. In conclusion, patients treated with SGLT-2 inhibitors did not have any significant difference in amputation occurrences compared to placebo across various studies. However, canagliflozin usage has led to higher amputation events in certain trials.

Genito Urinary Infection and Urinary Tract Infection in Patients with Type 2 Diabetes Mellitus Receiving SGLT2 Inhibitors: Evidence from a Systematic Literature Review of Landmark Randomized Clinical Trial.

SGLT2 inhibitors are class of drugs that are used in adults with type 2 diabetes through a novel mechanism of action by reducing renal tubular glucose reabsorption, leading to a reduction in blood glucose without stimulating insulin release. In this systematic review, we report the effects of treatment with SGLT2 inhibitors on urinary tract infection (UTI) and genitourinary infection (GUI). The study integrated data from landmark trials of SGLT2 inhibitors (CANVAS, CREDENCE, DECLARE-TIMI 58, and EMPA-REG) to interpret the association of SGLT2 inhibitors with genital infection (GI) and UTI. We reported the review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. The primary outcome was a composite of participants reporting UTI and GUI prescribed on SGLT2 inhibitors. The analysis of four studies involving 38,723 participants revealed incidences of both UTIs and GUI. In the SGLT2 inhibitor group, comprising 21,266 participants, 222 (1.04%) experienced UTIs, and 477 (2.24%) reported GUI. In contrast, among the placebo group consisting of 17,457 participants, 201 (1.15%) reported UTIs, and 70 (0.40%) reported genital infections. These findings underscore the elevated risk associated with SGLT2 inhibitor use, particularly regarding GUI, necessitating careful consideration in clinical practice and patient management strategies. The incidence of UTIs and particularly more pronounced GUI associated with SGLT2 inhibitors highlights the importance of careful risk assessment and monitoring in clinical decision-making, underscoring the need for patient management strategies.

Decline in use of high-risk agents for tight glucose control among older adults with diabetes in New York City: 2017-2022.

This study aimed to examine the prevalence of inappropriate tight glycemic control in older adults with type 2 diabetes and other chronic conditions in New York City, and to identify factors associated with this practice. We conducted a retrospective cohort study using the INSIGHT Clinical Research Network. The study population included 11,728 and 15,196 older adults in New York City (age ≥ 75 years) with a diagnosis of type 2 diabetes, and at least one other chronic medical condition, in 2017 and 2022, respectively. The main outcome of interest was inappropriate tight glycemic control, defined as HbA1c <7.0% (<53 mmol/mol) with prescription of at least one high-risk agent (insulin or insulin secretagogue). The proportion of older adults with inappropriate tight glycemic control decreased by nearly 19% over a five-year period (19.4% in 2017 to 15.8% in 2022). There was a significant decrease in insulin (27.8% in 2017; 24.3% in 2022) and sulfonylurea (29.4% in 2017; 21.7% in 2022) medication prescription, and increase in use of GLP-1 agonists (1.8% in 2017; 11.4% in 2022) and SGLT-2 inhibitors (5.8% in 2017; 25.1% in 2022), among the total population. Factors associated with inappropriate tight glycemic control in 2022 included history of heart failure (adjusted odds ratio [aOR] 1.38), chronic kidney disease ([aOR] 1.93), colorectal cancer ([aOR] 1.38), acute myocardial infarction ([aOR] 1.28), "other" ([aOR] 0.72) or "unknown" ([aOR] 0.72) race, and a point increase in BMI ([aOR] 0.98). We found an encouraging trend toward less use of high-risk medication strategies for older adults with type 2 diabetes and multiple chronic conditions. However, one in six patients in 2022 still had inappropriate tight glycemic control, indicating a need for continued efforts to optimize diabetes management in this population.

Management of Diabetes Mellitus in Acromegaly and Cushing's Disease with Focus on Pasireotide Therapy: A Narrative Review.

Patients suffering from acromegaly and Cushing's Disease (CD) face the risk of several clinical complications. The onset of diabetes mellitus (DM) is among the most important: exposure to elevated growth hormone or cortisol levels is associated with insulin resistance (IR). DM contributes to increasing cardiovascular risk for these subjects, which is higher compared to healthy individuals. Hyperglycemia may also be caused by pasireotide, a second-generation somatostatin receptor ligand (SRLs), currently used for the treatment of these diseases. Accordingly, with 2014 medical expert recommendations, the management of hyperglycemia in patients with CD and treated with pasireotide is based on lifestyle changes, metformin, DPP-4 inhibitors (DPP-4i) and, subsequently, GLP-1 Receptor Agonists (GLP-1 RAs). There is no position for SGLT2-inhibitors (SGLT2-i). However, a very recent experts' consensus regarding the management of pasireotide-induced hyperglycemia in patients with acromegaly suggests the use of GLP-1 RAs as first line treatment (in suitable patients) and the use of SGLT2-i as second line treatment in patients with high cardiovascular risk or renal disease. As a matter of fact, beyond the hypoglycemic effect of GLP1-RAs and SGLT2-i, there is increasing evidence regarding their role in the reduction of cardiovascular risk, commonly very high in acromegaly and CD and often tough to improve despite biochemical remission. So, an increasing use of GLP1-RAs and SGLT2-i to control hyperglycemia is desirable in these diseases. Obviously, all of that must be done with due attention in order to minimize the occurrence of adverse events. For this reason, large studies are needed to analyze the presence of potential limitations.

Combination of SGLT2 Inhibitors and GLP-1 Receptor Agonists in PTDM Treatment in Kidney Transplant Recipients: Synergistic Effect With Added Value in Terms of Nephroprotection

Post-transplantation diabetes mellitus, obesity, and metabolic syndrome are common complications after kidney transplantation. Data on using novel agents, including SGLT2 inhibitors and GLP-1 receptor agonists, in kidney transplant recipients are scarce and practice guidelines are lacking. According to available data, GLP-1 receptor agonists are efficient in terms of weight loss and glycemia control. Although improvement or no change of eGFR was observed, recently published data suggest their protective effect on graft function. Trials on SGLT2 inhibitors demonstrate improved glycemia control, weight, and blood, and stable kidney function. Given the different mechanisms of action, it has been postulated that a combination of SGLT2 inhibitors and GLP-1 receptor agonist could have beneficial effects in treating diabetes. There is some evidence in the literature postulating the beneficial effects of this treatment combination on cardiovascular outcomes in the general population and only one case emphasizing nephroprotective effect. Data on simultaneous use of SGLT2 inhibitors and GLP-1 receptor agonists in kidney transplant recipients is lacking and, here, we bring our experience.

The association between the utilization of SGLT2 inhibitors and diabetic retinopathy; a systematic review and meta-analysis of cohort studies

Introduction: Diabetic retinopathy is one of the principal causes of blindness globally. The impact of sodium-glucose cotransporter 2 (SGLT-2) inhibitors, a category of anti-diabetic medications, on diabetic retinopathy remains undetermined. Consequently, this study aimed to examine the association between the utilization of SGLT2 inhibitors and the incidence of diabetic retinopathy. Materials and Methods: This investigation systematically searched databases, including Web of Science, Cochrane, ProQuest, PubMed, and Google Scholar, until March 7, 2024. A systematic review and meta-analysis methodology was employed. Data were analyzed using STATA software version 14, considering a significance level of tests at P&lt;0.05. Results: The application of SGLT2 inhibitors was connected with a diminished diabetic retinopathy risk (odds ratio [OR]: 0.77, 95% CI: 0.69, 0.86). Among women, SGLT2 inhibitor use did not notably influence diabetic retinopathy risk (OR: 0.84, 95% CI: 0.69, 1.03). However, among men, employing SGLT2 inhibitors decreased the risk (OR: 0.81, 95% CI: 0.71, 0.92). In comparison to dipeptidyl peptidase-4 inhibitors (OR: 0.70, 95% CI: 0.53, 0.94) and pioglitazone (OR: 0.75, 95% CI: 0.74, 0.76), SGLT2 inhibitors lowered the risk of diabetic retinopathy. However, when compared to sulfonylureas (OR: 0.45, 95% CI: 0.17, 1.17) and GLP1-RA (OR: 0.70, 95% CI: 0.42, 1.17), SGLT2 inhibitors did not notably affect diabetic retinopathy. Moreover, using SGLT2 inhibitors in the age groups of 50-54 years (OR: 0.74, 95% CI: 0.55, 0.98), 55-59 years (OR: 0.65, 95% CI: 0.53, 0.79), and 60-64 years (OR: 0.89, 95% CI: 0.82, 0.97) was linked to lower diabetic retinopathy risk. Nevertheless, in the 65-69 age group, SGLT2 inhibitor administration did not significantly alter the diabetic retinopathy risk (OR: 1.04, 95% CI: 0.94, 1.15). Conclusion: The intake of SGLT2 inhibitors has been linked to a diminution in the hazard of diabetic retinopathy. However, further research in this domain is recommended, given the need for studies examined. Registration: This study has been compiled based on the PRISMA checklist, and its protocol was registered on the PROSPERO (CRD42024523959) and Research Registry (UIN: reviewregistry1808) website.