Population Trends of New Prescriptions for Antihyperglycemics and Antihypertensives Between 2014 and 2022.

BACKGROUND: In the wake of pandemic-related health decline and health care disruptions, there are concerns that previous gains for cardiovascular risk factors may have stalled or reversed. Population-level excess burden of drug-treated diabetes and hypertension during the pandemic compared with baseline is not well characterized. We evaluated the change in incident prescription claims for antihyperglycemics and antihypertensives before versus during the pandemic. METHODS AND RESULTS: In this retrospective, serial, cross-sectional, population-based study, we used interrupted time series analyses to examine changes in the age- and sex-standardized monthly rate of incident prescriptions for antihyperglycemics and antihypertensives in patients aged ≥66 years in Ontario, Canada, before the pandemic (April 2014 to March 2020) compared with during the pandemic (July 2020 to November 2022). Incident claim was defined as the first prescription filled for any medication in these classes. The characteristics of patients with incident prescriptions of antihyperglycemics (n=151 888) or antihypertensives (n=368 123) before the pandemic were comparable with their pandemic counterparts (antihyperglycemics, n=97 015; antihypertensives, n=146 524). Before the pandemic, monthly rates of incident prescriptions were decreasing (-0.03 per 10 000 individuals [95% CI, -0.04 to -0.01] for antihyperglycemics; -0.14 [95% CI, -0.18 to -0.10] for antihypertensives). After July 2020, monthly rates increased (postinterruption trend 0.31 per 10 000 individuals [95% CI, 0.28-0.34] for antihyperglycemics; 0.19 [95% CI, 0.14-0.23] for antihypertensives). CONCLUSIONS: Population-level increases in new antihyperglycemic and antihypertensive prescriptions during the pandemic reversed prepandemic declines and were sustained for >2 years. Our findings are concerning for current and future cardiovascular health.

Sodium Glucose Transporter 2 Inhibitors Versus Metformin on Cardiovascular and Renal Outcomes in Patients With Diabetes With Low Cardiovascular Risk: A Nationwide Cohort Study.

BACKGROUND: This study investigated whether initial SGLT2 (sodium-glucose cotransporter 2) inhibitor-based treatment is superior to metformin-based regimens as a primary prevention strategy among low-risk patients with diabetes. METHODS AND RESULTS: In this nationwide cohort study, a total of 38 496 patients with diabetes with low cardiovascular risk were identified (age 62.0±11.6 years, men 50%) from January 1 to December 31, 2016. Patients receiving SGLT2 inhibitors-based and metformin-based regimens were 1:2 matched by propensity score. Study outcomes included all-cause mortality, cardiovascular death, hospitalization for heart failure, stroke, and progression to end-stage renal disease. Compared with 1928 patients receiving metformin-based regimens, 964 patients receiving SGLT2 inhibitor-based regimens had similar all-cause mortality (hazard ratio [HR], 0.75 [95% CI, 0.51-1.12]), cardiovascular death (HR, 0.69 [95% CI, 0.25-1.89]), hospitalization for heart failure (HR, 1.06 [95% CI, 0.59-1.92]), stroke (HR, 0.78 [95% CI, 0.48-1.27]), and progression to end-stage renal disease (HR, 0.88 [95% CI, 0.32-2.39]). However, SGLT2 inhibitors were associated with a lower risk of all-cause mortality (HR, 0.47 [95% CI, 0.23-0.99]; P for interaction=0.008) and progression to end-stage renal disease (HR, 0.22 [95% CI, 0.06-0.82]; P for interaction=0.04) in patients under the age of 65. CONCLUSIONS: In comparison to metformin-based regimens, SGLT2 inhibitor-based regimens showed a similar risk of all-cause mortality and adverse cardiorenal events. SGLT2 inhibitors might be considered as first-line therapy in select low-risk patients, for example, younger patients with diabetes.

Current barriers to initiating insulin therapy in individuals with type 2 diabetes.

Insulin is an essential drug in the treatment of diabetes, often necessary for managing hyperglycemia in type 2 diabetes mellitus (T2DM). It should be considered in cases of severe hyperglycemia requiring hospitalization, after the failure of other treatments, in advanced chronic kidney disease, liver cirrhosis, post-transplant diabetes, or during pregnancy. Moreover, in specific patient subgroups, early initiation of insulin is crucial for hyperglycemia control and prevention of chronic complications. Clinical guidelines recommend initiating insulin when other treatments fail, although there are barriers that may delay its initiation. The timing of initiation depends on individual patient characteristics. Typically, insulinization starts by adding basal insulin to the patient's existing treatment and, if necessary, progresses by gradually introducing prandial insulin. Several barriers have been identified that hinder the initiation of insulin, including fear of hypoglycemia, lack of adherence, the need for glucose monitoring, the injection method of insulin administration, social rejection associated with the stigma of injections, weight gain, a sense of therapeutic failure at initiation, lack of experience among some healthcare professionals, and the delayed and reactive positioning of insulin in recent clinical guidelines. These barriers contribute, among other factors, to therapeutic inertia in initiating and intensifying insulin treatment and to patients' non-adherence. In this context, the development of once-weekly insulin formulations could improve initial acceptance, adherence, treatment satisfaction, and consequently, the quality of life for patients. Currently, two once-weekly basal insulins, insulin icodec and basal insulin BIF, which are in different stages of clinical development, may help. Their longer half-life translates to lower variability and reduced risk of hypoglycemia. This review addresses the need for insulin in T2DM, its positioning in clinical guidelines under specific circumstances, the current barriers to initiating and intensifying insulin treatment, and the potential role of once-weekly insulin formulations as a potential solution to facilitate timely initiation of insulinization, which would reduce therapeutic inertia and achieve better early control in people with T2DM.

[Patient with type 2 diabetes and coronary heart disease developing heart failure]. / Vignette thérapeutique de l'étudiant. Patient avec un diabète de type 2, une coronaropathie et une insuffisance cardiaque.

Patients with type 2 diabetes (T2D) are frequently exposed to comorbidities, mainly cardiovascular complications. Thus, a polypharmacy is often mandatory, targeting not only T2D but also comorbidities such as coronary artery disease and heart failure. Interestingly, some drugs improve glucose control, cardiovascular prognosis and heart failure outcome. This versatility may cause trouble regarding prescriptions by practitioners, especially because of the restricted conditions for the reimbursement in Belgium. This clinical vignette aims at discussing the path of pharmacotherapy for a patient with T2D who suffers from a myocardial infarction and subsequently develops a heart failure. It will mainly focus on the place of glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporters 2 (gliflozins) as well as the potential of their combination in this context, considering the current restrictions for the reimbursement.

Le patient avec un diabète de type 2 (DT2) est souvent exposé à diverses comorbidités, notamment cardiovasculaires. Dès lors, une polymédication est souvent nécessaire, ciblant le DT2 lui-même, mais aussi les comorbidités comme une coronaropathie et une insuffisance cardiaque. De façon intéressante, certaines médications améliorent à la fois le contrôle glycémique, le pronostic cardiovasculaire et le devenir de l'insuffisance cardiaque. Cette polyvalence peut jeter le trouble en ce qui concerne les prescriptions chez les praticiens, notamment en lien avec les conditions restrictives de remboursement en Belgique. Cette vignette clinique a pour but d'illustrer le cheminement de la pharmacothérapie d'un patient avec un DT2 qui présente un infarctus du myocarde puis, secondairement, une insuffisance cardiaque. Elle ciblera surtout la place des agonistes des récepteurs du glucagon-like peptide-1 et des inhibiteurs des cotransporteurs sodium-glucose de type 2 (gliflozines), et expliquera l'intérêt de leur combinaison dans ce contexte en tenant compte des conditions actuelles de remboursement.

The association between sodium glucose cotransporter-2 inhibitors vs dipeptidyl peptidase-4 inhibitors and renal outcomes in people discharged from hospital with type 2 diabetes: A population-based cohort study.

BACKGROUND: We investigated the association between post-hospital discharge use of sodium glucose cotransporter-2 inhibitors (SGLT-2is) compared to dipeptidyl peptidase-4 inhibitors (DPP-4is) and the incidence of hospitalization for acute renal failure (ARF) and chronic kidney disease (CKD) in people with type 2 diabetes. METHODS: We conducted a retrospective cohort study using linked hospital and prescription data. Our cohort included people aged ≥30 years with type 2 diabetes discharged from a hospital in Victoria, Australia, from December 2013 to June 2018. We compared new users of SGLT-2is with new users of DPP-4is following discharge. People were followed from first dispensing of a SGLT-2i or DPP-4i to a subsequent hospital admission for ARF or CKD. We used competing risk models with inverse probability of treatment weighting (IPTW) to estimate subhazard ratios. RESULTS: In total, 9620 people initiated SGLT-2is and 9962 initiated DPP-4is. The incidence rate of ARF was 12.3 per 1000 person-years (median years of follow-up [interquartile range [IQR] 1.4 [0.7-2.2]) among SGLT-2i initiators and 18.9 per 1000 person-years (median years of follow-up [IQR] 1.7 [0.8-2.6]) among DPP-4i initiators (adjusted subhazard ratio with IPTW 0.78; 95% confidence interval [CI] 0.70-0.86). The incidence rate of CKD was 6.0 per 1000 person-years (median years of follow-up [IQR] 1.4 [0.7-2.2]) among SGLT-2i initiators and 8.9 per 1000 person-years (median years of follow-up [IQR] 1.7 [0.8-2.6]) among DPP-4i initiators (adjusted subhazard ratio with IPTW 0.83; 95% CI 0.73-0.94). CONCLUSIONS: Real-world data support using SGLT-2is over DPP-4is for preventing acute and chronic renal events in people with type 2 diabetes.

Relationship between electrolytes and glycated hemoglobin among diabetic patients with poor adherence to antidiabetic medications: a cross-sectional study.

Introduction: type 2 Diabetes mellitus is a chronic metabolic disease with devastating effects on patients and results in numerous healthcare challenges in terms of its management and the cost burden among the affected. Successful management involves maintaining optimal glycemic control to prevent complications, with adherence to antidiabetic medications playing a crucial role in achieving this objective. Additionally, maintaining a healthy electrolyte balance is key for overall well-being and physiological function. However, the correlation between glycated hemoglobin and electrolyte balance remains under investigated, particularly in patients with suboptimal adherence. The aim of this research was to study the relationship between glycated hemoglobin and electrolytes among diabetic patients with poor adherence to antidiabetic medications. Methods: this study was conducted at Samburu County Referral Hospital in Samburu County, Kenya. We employed a descriptive cross-sectional design focusing on adult diabetic patients aged 18 years and above who had visited the diabetic clinic over a three-month period. To evaluate their adherence levels, we employed a Morisky Medication Adherence Scale-8. Seventy-two diabetic patients who got adherence level scores of < 6 were categorized as having low adherence and their blood samples were collected for measuring glycated hemoglobin levels and electrolytes levels particularly potassium, sodium, calcium, magnesium, phosphorus and chloride. Relationship between electrolytes and glycated hemoglobin among diabetic patients with poor adherence to antidiabetics was determined using Karl Pearson correlation. Results: among the study participants, the lowest hemoglobin A1C (HbA1c) level recorded was 5.1% while the highest was 15.0% and the majority (41.7%) fell within the HbA1c range of 5-7%. A high proportion of individuals (58.3%) with poor adherence to antidiabetics had elevated HbA1c levels, indicating poor glycemic control. The correlations observed between glycated hemoglobin and electrolytes which included magnesium, sodium, chloride, calcium and phosphorus was r= -0.07, -0.32, -0.05 -0.24 and -0.04 respectively. Conclusion: this study concluded that there is a relationship between electrolytes and glycated hemoglobin among diabetic patients with poor adherence to antidiabetics. A statistically significant negative correlation was observed between glycated hemoglobin and calcium level (r=-0.2398 P ≤0.05) and also sodium (r=-0.31369 P≤0.05). A negative correlation (P≥0.05) was observed between phosphorus, magnesium, chloride and potassium with HbA1c levels though not statistically significant.

Efficacy and safety of basal insulins in people with type 2 diabetes mellitus: a systematic review and network meta-analysis of randomized clinical trials.

Aim: The comparative effectiveness of basal insulins has been examined in several studies. However, current treatment algorithms provide a list of options with no clear differentiation between different basal insulins as the optimal choice for initiation. Methods: A comprehensive search of MEDLINE, Embase, Cochrane Library, ISI, and Scopus, and a reference list of retrieved studies and reviews were performed up to November 2023. We identified phase III randomized controlled trials (RCTs) comparing the efficacy and safety of basal insulin regimens. The primary outcomes evaluated were HbA1c reduction, weight change, and hypoglycemic events. The revised Cochrane ROB-2 tool was used to assess the methodological quality of the included studies. A random-effects frequentist network meta-analysis was used to estimate the pooled weighted mean difference (WMD) and odds ratio (OR) with 95% confidence intervals considering the critical assumptions in the networks. The certainty of the evidence and confidence in the rankings was assessed using the GRADE minimally contextualized approach. Results: Of 20,817 retrieved studies, 44 RCTs (23,699 participants) were eligible for inclusion in our network meta-analysis. We found no significant difference among various basal insulins (including Neutral Protamine Hagedorn (NPH), ILPS, insulin glargine, detemir, and degludec) in reducing HbA1c. Insulin glargine, 300 U/mL (IGlar-300) was significantly associated with less weight gain (mean difference ranged from 2.9 kg to 4.1 kg) compared to other basal insulins, namely thrice-weekly insulin degludec (IDeg-3TW), insulin degludec, 100 U/mL (IDeg-100), insulin degludec, 200 U/mL (IDeg-200), NPH, and insulin detemir (IDet), but with low to very low certainty regarding most comparisons. IDeg-100, IDeg-200, IDet, and IGlar-300 were associated with significantly lower odds of overall, nocturnal, and severe hypoglycemic events than NPH and insulin lispro protamine (ILPS) (moderate to high certainty evidence). NPH was associated with the highest odds of overall and nocturnal hypoglycemia compared to others. Network meta-analysis models were robust, and findings were consistent in sensitivity analyses. Conclusion: The efficacy of various basal insulin regimens is comparable. However, they have different safety profiles. IGlar-300 may be the best choice when weight gain is a concern. In contrast, IDeg-100, IDeg-200, IDet, and IGlar-300 may be preferred when hypoglycemia is the primary concern.

Psychosocial Factors and Glycemic Control in Young Adults With Youth-Onset Type 2 Diabetes.

Importance: Youth-onset type 2 diabetes is associated with poor glycemic control and early onset of complications. Identification of psychosocial factors associated with poor glycemic control is needed to inform efficacious interventions. Objective: To identify psychosocial factors associated with glycated hemoglobin (HbA1c) levels in young adults with youth-onset type 2 diabetes. Design, Setting, and Participants: For the iCount cohort study, HbA1c levels were measured twice (at baseline [T1] and at 1 year [T2]) during the last years (2017-2019) of the observational phase of the multicenter Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY2) study. Participants were young adults who had been diagnosed with type 2 diabetes during childhood or adolescence. Data were analyzed from December 2021 to September 2023. Main Outcomes and Measures: Glycemic control was examined categorically (high [≥8.0%] vs low [<8.0%] HbA1c), continuously (HbA1c level), and over time (change in HbA1c: decreased ≥0.5%, remained stable, or increased ≥0.5%). Psychosocial measures included beliefs about medicines, depression and anxiety symptoms, diabetes distress, diabetes self-efficacy, self-management support, and unmet material needs. Multivariable logistic and linear regression models evaluated the association of each psychosocial factor with the probability of T2 HbA1c of 8.0% or greater, T2 HbA1c level, and change in HbA1c. Results: Of the 411 TODAY2 participants approached, 381 enrolled in the iCount study, and 348 with T1 and T2 HbA1c data comprised the analysis group. The 348 participants had a mean (SD) age of 26.1 (2.5) years and a mean (SD) HbA1c of 9.4% (2.8%). Most participants (229 [65.8%]) were women. In adjusted multivariable regressions, greater beliefs that diabetes medicines are necessary (odds ratio [OR], 1.19 [95% CI, 1.03-1.37]; P = .02), concerns about medicines (OR, 1.20 [95% CI, 1.00-1.45]; P = .049), diabetes distress (OR, 1.08 [95% CI, 1.02-1.15]; P = .006), and high distress (OR, 2.18 [95% CI, 1.15-4.13]; P = .02) increased the odds of high HbA1c at T2. Greater support (OR, 0.67 [95% CI, 0.46-0.97]; P = .04) and diabetes self-efficacy (OR, 0.91 [95% CI, 0.84-0.99]; P = .02) decreased the odds of high HbA1c at T2. Diabetes distress was associated with higher HbA1c level at T2 (coefficient, 0.08 [95% CI, 0.02-0.13]; P = .01). Beliefs that diabetes medicines are necessary (OR, 1.20 [95% CI, 1.03-1.39]; P = .02) and concerns about medicines (OR, 1.22 [95% CI, 1.00-1.47]; P = .048) increased the odds of an HbA1c decrease of at least 0.5% over 1 year. Conclusions and Relevance: In this cohort study of young adults with youth-onset type 2 diabetes, beliefs about medicines, high diabetes distress, low diabetes self-efficacy, and self-management support were associated with high HbA1c over time. Future research should assess whether interventions that address these factors result in improved glycemic control in this at-risk group.

Trends in antidiabetic drug use and expenditure in public hospitals in Northwest China, 2012-21: a case study of Gansu Province.

BACKGROUND: Since the twenty-first century, the prevalence of diabetes has risen globally year by year. In Gansu Province, an economically underdeveloped province in northwest China, the cost of drugs for diabetes patients accounted for one-third of their total drug costs. To fundamentally reduce national drug expenditures and the burden of medication on the population, the relevant departments of government have continued to reform and improve drug policies. This study aimed to analyse long-term trends in antidiabetic drug use and expenditure in Gansu Province from 2012 to 2021 and to explore the role of pharmaceutical policy. METHODS: Data were obtained from the provincial centralised bidding and purchasing (CBP) platform. Drug use was quantified using the anatomical therapeutic chemistry/defined daily dose (ATC/DDD) method and standardised by DDD per 1000 inhabitants per day (DID), and drug expenditure was expressed in terms of the total amount and defined daily cost (DDC). Linear regression was used to analyse the trends and magnitude of drug use and expenditure. RESULTS: The overall trend in the use and expenditure of antidiabetic drugs was on the rise, with the use increasing from 1.04 in 2012 to 16.02 DID in 2021 and the expenditure increasing from 48.36 in 2012 to 496.42 million yuan in 2021 (from 7.66 to 76.95 million USD). Some new and expensive drugs changed in the use pattern, and their use and expenditure shares (as the percentage of all antidiabetic drugs) increased from 0 to 11.17% and 11.37%, but insulins and analogues and biguanides remained the most used drug class. The DDC of oral drugs all showed a decreasing trend, but essential medicines (EMs) and medical insurance drugs DDC gradually decreased with increasing use. The price reduction of the bid-winning drugs was over 40%, and the top three drugs were glimepiride 2mg/30, acarbose 50mg/30 and acarbose 100mg/30. CONCLUSIONS: The implementation of pharmaceutical policies has significantly increased drug use and expenditure while reducing drug prices, and the introduction of novel drugs and updated treatment guidelines has led to changes in use patterns.

Comparing Equil patch versus traditional catheter insulin pump in type 2 diabetes using continuous glucose monitoring metrics and profiles.

AIMS: It is not clear whether there are differences in glycemic control between the Equil patch and the MMT-712 insulin pump. Our objective was to compare two types of insulin pumps in the treatment of type 2 diabetes mellitus (T2DM), using continuous glucose monitoring (CGM) metrics and profiles. METHODS: This was a randomized case-crossover clinical trial. Participants were hospitalized and randomly allocated to two groups and underwent two types of insulin pump treatments (group A: Equil patch-Medtronic MMT-712 insulin pump; group B: Medtronic MMT-712-Equil patch insulin pump) separated by a 1-day washout period. Glycemic control was achieved after 7-8 days of insulin pump therapy. Each patient received CGM for 5 consecutive days (from day 1 to day 5). On day 3 of CGM performance, the Equil patch insulin pump treatment was switched to Medtronic MMT-712 insulin pump treatment at the same basal and bolus insulin doses or vice versa. CGM metrics and profiles including glycemic variability (GV), time in range (TIR, 3.9-10.0 mmol/L), time below range (TBR, <3.9 mmol/L), time above range (TAR, >10.0 mmol/L), and postprandial glucose excursions, as well as incidence of hypoglycemia. RESULTS: Forty-six T2DM patients completed the study. There was no significant difference in parameters of daily GV and postprandial glucose excursions between the Equil patch insulin pump treatment and the Medtronic insulin pump treatment. Similarly, there was no between-treatment difference in TIR, TBR, and TAR, as well as the incidence of hypoglycemia. CONCLUSION: The Equil patch insulin pump was similar to the traditional MMT-712 insulin pump in terms of glycemic control. Equil patch insulin pump is a reliable tool for glycemic management of diabetes mellitus.

Sociodemographic disparities in sodium-glucose cotransporter-2 inhibitor use among US kidney transplant recipients: An observational study of real-world pharmacy records.

BACKGROUND: Recent clinical trials demonstrate benefits of sodium-glucose cotransporter-2 inhibitors (SGLT2i) in patients with chronic kidney disease, but data on use in kidney transplant (KTx) recipients are limited. METHODS: We examined a novel database linking SRTR registry data for KTx recipients (2000-2021) with outpatient fill records from a large pharmaceutical claims warehouse (2015-2021). Adult (≥18 years) KTx recipients treated with SGLT2i were compared to those who received other noninsulin diabetes medications without SGLT2i. Characteristics associated with SGLT2i use were quantified by multivariable logistic regression (adjusted odds ratio, 95%LCLaOR95%UCL). RESULTS: Among 18 988 KTx recipients treated with noninsulin diabetes agents in the study period, 2224 filled an SGLT2i. Mean time from KTx to prescription was 6.7 years for SGLT2i versus 4.7 years for non-SGLT2i medications. SGLT2i use was more common in Asian adults (aOR, 1.091.311.58) and those aged > 30-59 years (compared with 18-30 years) or with BMI > 35 kg/m2 (aOR, 1.191.411.67), and trended higher with self-pay status. SGLT2i use was lower among KTx recipients who were women (aOR, .79.87.96), Black (aOR, .77.881.00) and other (aOR, .52.751.07) race, publicly insured (aOR, .82.921.03), or with less than college education (aOR, .78.87.96), and trended lower in those age 75 years and older. SGLT2i use in KTx patients increased dramatically in 2019-2021 (aOR, 5.015.636.33 vs. prior years). CONCLUSION: SGLT2i use is increasing in KTx recipients but varies with factors including race, education, and insurance. While ongoing study is needed to define risks and benefits of SGLT2i use in KTx patients, attention should also focus on reducing treatment disparities related to sociodemographic traits.

PPAR agonists as add-on treatment with metformin in management of type 2 diabetes: a systematic review and meta-analysis.

The combination of metformin and the peroxisome proliferator-activated receptors (PPAR) agonists offers a promising avenue for managing type 2 diabetes (T2D) through their potential complementary mechanisms of action. The results from randomized controlled trials (RCT) assessing the efficacy of PPAR agonists plus metformin versus metformin alone in T2D are inconsistent, which prompted the conduct of the systematic review and meta-analysis. We searched MEDLINE and EMBASE from inception (1966) to March 2023 to identify all RCTs comparing any PPAR agonists plus metformin versus metformin alone in T2D. Categorical variables were summarized as relative risk along with 95% confidence interval (CI). Twenty RCTs enrolling a total of 6058 patients met the inclusion criteria. The certainty of evidence ranged from moderate to very low. Pooled results show that using PPAR agonist plus metformin, as compared to metformin alone, results in lower concentrations of fasting glucose [MD = - 22.07 mg/dl (95% CI - 27.17, - 16.97), HbA1c [MD = - 0.53% (95% CI - 0.67, - 0.38)], HOMA-IR [MD = - 1.26 (95% CI - 2.16, - 0.37)], and fasting insulin [MD = - 19.83 pmol/L (95% CI - 29.54, - 10.13)] without significant increase in any adverse events. Thus, synthesized evidence from RCTs demonstrates the beneficial effects of PPAR agonist add-on treatment versus metformin alone in T2D patients. In particular, novel dual PPARα/γ agonist (tesaglitazar) demonstrate efficacy in improving glycaemic and lipid concentrations, so further RCTs should be performed to elucidate the long-term outcomes and safety profile of these novel combined and personalized therapeutic strategies in the management of T2D.PROSPERO registration no. CRD42023412603.

Genitourinary Tract Infections in Patients Taking SGLT2 Inhibitors: JACC Review Topic of the Week.

Sodium-glucose cotransporter-2 inhibitors (SGLT2is) have been shown to reduce adverse cardiovascular events in patients with type 2 diabetes mellitus, all-cause mortality, and heart failure hospitalization in patients with heart failure, as well as adverse renal outcomes. However, concerns regarding the heightened risk of genitourinary (GU) infections, particularly urinary tract infections, remain a significant barrier to their wider adoption. Addressing these misconceptions using existing evidence is needed to ensure proper risk-benefit assessment and optimal utilization of this efficacious therapy. This review aims to provide a balanced perspective on the evidence-based cardiovascular and renal benefits of SGLT2is and the associated risk of GU infections. We also summarize and propose clinical practice considerations for SGLT2i-associated GU infections focusing on patients with cardiovascular disease.

Medication persistence and its impact on type 2 diabetes.

OBJECTIVES: Medication persistence in type 2 diabetes (T2D) is a critical factor for preventing adverse clinical events. We assessed persistence among newly treated patients with T2D and documented the impact of persistence on clinical outcomes and costs. STUDY DESIGN: Retrospective study of Optum Clinformatics Data Mart commercial and Medicare Advantage enrollees from 2007 to 2020. METHODS: We identified adult patients who initiated antidiabetic treatments. Patients were required to have at least 1 treatment-free year prior to their first T2D prescription. Persistence was measured as the duration of continuous therapy until a 60-day gap in drug availability appeared in any antidiabetic therapy. Factors associated with duration were documented, focusing on the initial class(es) of T2D drugs. The impact of treatment duration on the risk of hospitalization and on total health care costs was also examined. RESULTS: A total of 673,265 patients were included, with a median follow-up of 7 years. Only 22% of patients maintained continuous treatment, of whom 10% added a second medication. A 1-month increase in duration was associated with reduced risk of hospitalization due to stroke by 0.54% (95% CI, 0.46%-0.60%), acute myocardial infarction by 0.51% (95% CI, 0.44%-0.57%), and all-cause hospitalization by 0.36% (95% CI, 0.34%-0.37%). A 1-month increase in duration was associated with a year-to-year decrease in medical costs of $51 (95% CI, -$54 to -$48) and an increase in year-to-year drug costs of $14 (95% CI, $13-$14). CONCLUSIONS: Our findings show low persistence among patients with T2D and emphasize the importance of medication persistence, which is associated with cost savings and lower risk of hospitalizations.

Edible wild plants, chicory and purslane, alleviated diabetic testicular dysfunction, and insulin resistance via suppression 8OHdg and oxidative stress in rats.

Testicular dysfunction is a prevalent health problem frequently reported in individuals with diabetes mellitus (DM). Oxidative-inflammatory reactions, hormonal and spermatic abnormalities often accompany this illness. Herbal remedies "particularly wild plants" including chicory (Chicorium Intybus) and purslane (Portulaca Oleracea) are emerging as popular agents for people dealing with these issues due to their ability to act as antioxidants, reduce inflammation, and exhibit antidiabetic effects. According to the collected data, the daily administration of chicory (Ch) seed-extract (250 mg/kg) or purslane (Pu) seed-extract (200 mg/kg) to streptozotocin (STZ)-induced diabetic rats (50 mg/kg) for 30 days resulted in the normalization of fasting blood glucose (FBG), serum fructosamine, insulin levels, and insulin resistance (HOMA-IR), as well as reducing lipid peroxidation end-product malondialdehyde (MDA) level, aldehyde oxidase (AO) and xanthene oxidase (XO) activities. While caused a considerable improvement in glutathione (GSH) content, superoxide dismutase (SOD), catalase (CAT) activity, and total antioxidant capacity (TAC) when compared to diabetic rats. Ch and Pu extracts had a substantial impact on testicular parameters including sperm characterization, testosterone level, vimentin expression along with improvements in body and testis weight. They also mitigated hyperlipidemia by reducing total lipids (TL), total cholesterol (TC) levels, and low-density lipoprotein cholesterol (LDL-C), while increasing high-density lipoprotein cholesterol (HDL-C). Furthermore, oral administration of either Ch or Pu notably attuned the elevated proinflammatory cytokines as tumor necrotic factor (TNF-α), C-reactive protein (CRP), and Interleukin-6 (IL-6) together with reducing apoptosis and DNA damage. This was achieved through the suppression of DNA-fragmentation marker 8OHdG, triggering of caspase-3 immuno-expression, and elevation of Bcl-2 protein. The histological studies provided evidence supporting the preventive effects of Ch and Pu against DM-induced testicular dysfunction. In conclusion, Ch and Pu seed-extracts mitigate testicular impairment during DM due to their antihyperglycemic, antilipidemic, antioxidant, anti-inflammatory, and antiapoptotic properties.

Intensive management from diagnosis improves HbA1c at 12 months post-diagnosis: results from a prospective cohort study in children with newly diagnosed type 1 diabetes.

AIMS: To examine the impact of intensive management of type 1 diabetes (T1D) from diagnosis on HbA1c 12 months from diagnosis. METHODS: HbA1c measured 12 months after diagnosis for 70 consecutively newly diagnosed children with T1D following implementation of an intensive management protocol was compared with 70 children consecutively diagnosed immediately pre-implementation. Intensive management involved carbohydrate counting and flexible insulin dosing from first meal with subcutaneous insulin, targeted blood glucose levels from 4-8mmol/L irrespective of time of day, avoidance of twice daily insulin regimen and promotion of continuous glucose monitoring (CGM). HbA1c, diabetes technology use and insulin regimen at 12 months post-diagnosis were compared. RESULTS: The post-intensive management implementation cohort had an improved mean HbA1c of 58.2±15.3mmol/mol vs 63.7±10.7mmol/mol at 12 months (p=0.014). The proportion of young people with diabetes meeting a target HbA1c of <53mmol/mol at 12 months improved from 11% to 40% (p=<0.001). There was a reduction of twice daily insulin regimen from 66% to 11% (p=<0.001), and increased CGM use from 57% to 76% (p=0.02). CONCLUSION: Intensive management when implemented with consistent messaging from the multi-disciplinary team resulted in clinic-wide improvements in HbA1c and the proportion meeting HbA1c targets.