Classes Of Diabetes Medications Research Articles

Clinical pharmacist practitioners on primary care teams play an important role in caring for complex patients with diabetes.

In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. To evaluate whether clinical pharmacist practitioners (CPPs) are being utilized to care for patients with complex medication regimens and multiple chronic illnesses, we compared the clinical complexity of diabetes patients referred to CPPs in team primary care and those in care by other team providers (OTPs). In this cross-sectional comparison of patients with diabetes in the US Department of Veterans Affairs (VA) healthcare system in the 2017-2019 period, patient complexity was based on clinical factors likely to indicate need for more time and resources in medication and disease state management. These factors include insulin prescriptions; use of 3 or more other diabetes medication classes; use of 6 or more other medication classes; 5 or more vascular complications; metabolic complications; 8 or more other complex chronic conditions; chronic kidney disease stage 3b or higher; glycated hemoglobin level of ≥10%; and medication regime nonadherence. Patients with diabetes referred to one of 110 CPPs for care (n = 12,728) scored substantially higher (P < 0.001) than patients with diabetes in care with one of 544 OTPs (n = 81,183) on every complexity measure, even after adjustment for age, sex, race, and marital status. Based on composite summary scores, the likelihood of complexity was 3.42 (interquartile range, 3.25-3.60) times higher for those in ongoing CPP care (ie, those with 2 or more visits) versus OTP care. Patients in CPP care also were, on average, younger, more obese, and had more prior outpatient visits and hospital stays. The greater complexity of patients with diabetes seen by CPPs in primary care suggests that CPPs are providing valuable services in comprehensive medication and disease management of complex patients.

SGLT2 Inhibitors and Perioperative Euglycemic Diabetic Ketoacidosis

Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a new class of diabetes medications that act at the level of the kidney to increase renal glucose clearance. The resultant hypoglycemia suppresses insulin secretion and stimulates glucagon, lipolysis, and ketogenesis, which creates a state of starvation. Since SGLT2 inhibitors also decrease sodium reabsorption, patients are at risk for dehydration. An unusual side effect of this drug class is the development of euglycemic diabetic ketoacidosis (eDKA). A case report describes a patient taking Synjardy® (empagliflozin/metformin) who underwent laparoscopic cholecystectomy and developed perioperative eDKA. It is critical to maintain a high index of suspicion to recognize eDKA and institute immediate therapy tenants of intravenous fluid hydration, insulin infusion, and aggressive electrolyte repletion.

Expanded Use of Sodium Glucose Co-Transporter 2 Inhibitors: Evidence Beyond Heart Failure with Reduced Ejection Fraction.

Following the results observed in the DAPA-HF trial and subsequent FDA approval of dapagliflozin in patients living with heart failure with reduced ejection fraction (HFrEF), numerous trials quickly began to assess the effects of sodium glucose co-transporter 2 inhibitors (SGLT2i) in a wide range of CV (CV) conditions. Since publication of those findings, multiple SGLT2i have demonstrated benefit in patients regardless of left ventricular ejection fraction (LVEF) - allowing the drug class to establish itself within the first-line of guideline directed medication therapy. Although the full mechanistic properties of SGLT2i in heart failure (HF) has yet to be fully understand, benefits in other disease states have continued to emerge over the past decade. This review summarizes the findings of 14 clinical trials investigating the use of SGLT2i in various cardiovascular (CV) disease states, with a special focus on HF with preserved ejection fraction (HFpEF) and acute decompensated HF (ADHF). Additionally, studies assessing the CV-related mechanisms, cost-effectiveness, and exploratory effects of dual SGLT1/2 blockade are described. A review of select ongoing trials has also been incorporated to further characterize the research landscape with this medication class. The aim of this review is to serve as a comprehensive tool for healthcare providers to better understand how this class of diabetes medications established its place in the treatment of HF.

SGLT2 Inhibitors: Emerging Drugs in Heart Failure

Sodium-glucose cotransporter 2 (SGLT2) inhibitors constitute a class of diabetes medications that have demonstrated the potential to improve outcomes for heart failure (HF) patients. Although they were originally developed to treat diabetes, clinical trials have demonstrated their ability to both reduce the risk and improve the prognosis of HF. SGLT2 inhibitors have unique mechanisms of action, including improvement of water retention and promotion of lipolysis, which contribute to their effectiveness in treating HF. They are considered essential primary treatment options for patients with HF, regardless of diabetes status and ejection fraction. Overall, the use of SGLT2 inhibitors in patients with HF is expected to increase in the future and may further improve treatment outcomes for HF patients.

An Online, Multi-institutional Debate on Diabetes Medications by Advanced Pharmacy Practice Experience Students

Objective. The purpose of this study was to evaluate changes in advanced pharmacy practice experience (APPE) students' knowledge and to measure student perceptions of an online, multi-institutional debate curriculum as an alternative to a journal club to improve critical thinking skills related to diabetes medications.Methods. All APPE students assigned to four faculty (n=37) at three different colleges during the 2020-2021 academic year received instruction on diabetes medication classes and their cardiovascular outcome trials. Students debated via the Lincoln-Douglas format whether the preferred second-line therapies for patients with type 2 diabetes mellitus are either glucagon-like peptide-1 receptor agonists or sodium-glucose cotransporter-2 inhibitors. Matched pre- and post-APPE knowledge scores were measured using a seven-item assessment tool. A 22-item post-debate survey measured student perceptions of the activity.Results. Pre- and post-APPE knowledge scores were compared in 32 students, yielding an 86% response rate. Knowledge scores improved 32% (59% pre vs 87% post). Thirty-three students completed the perceptions survey, yielding an 89% response rate. Students reported that the debate activity was beneficial (100%) and rated it more effective than a journal club at improving critical thinking skills and knowledge retention.Conclusion. Preliminary results suggest that incorporating an online, multi-institutional debate as an alternative to journal clubs during APPE rotations was well received. Further research is warranted on the impact of the multi-institutional debate and how to best deliver it during the APPEs of a pharmacy curriculum.

Marginal Structural Models Using Calibrated Weights With SuperLearner: Application to Type II Diabetes Cohort.

As different scientific disciplines begin to converge on machine learning for causal inference, we demonstrate the application of machine learning algorithms in the context of longitudinal causal estimation using electronic health records. Our aim is to formulate a marginal structural model for estimating diabetes care provisions in which we envisioned hypothetical (i.e. counterfactual) dynamic treatment regimes using a combination of drug therapies to manage diabetes: metformin, sulfonylurea and SGLT-2i. The binary outcome of diabetes care provisions was defined using a composite measure of chronic disease prevention and screening elements [27] including (i) primary care visit, (ii) blood pressure, (iii) weight, (iv) hemoglobin A1c, (v) lipid, (vi) ACR, (vii) eGFR and (viii) statin medication. We used several statistical learning algorithms to describe causal relationships between the prescription of three common classes of diabetes medications and quality of diabetes care using the electronic health records contained in National Diabetes Repository. In particular, we generated an ensemble of statistical learning algorithms using the SuperLearner framework based on the following base learners: (i) least absolute shrinkage and selection operator, (ii) ridge regression, (iii) elastic net, (iv) random forest, (v) gradient boosting machines, and (vi) neural network. Each statistical learning algorithm was fitted using the pseudo-population generated from the marginalization of the time-dependent confounding process. Covariate balance was assessed using the longitudinal (i.e. cumulative-time product) stabilized weights with calibrated restrictions. Our results indicated that the treatment drop-in cohorts (with respect to metformin, sulfonylurea and SGLT-2i) may have improved diabetes care provisions in relation to treatment naïve (i.e. no treatment) cohort. As a clinical utility, we hope that this article will facilitate discussions around the prevention of adverse chronic outcomes associated with type II diabetes through the improvement of diabetes care provisions in primary care.

A calibration approach to transportability and data-fusion with observational data.

Two important considerations in clinical research studies are proper evaluations of internal and external validity. While randomized clinical trials can overcome several threats to internal validity, they may be prone to poor external validity. Conversely, large prospective observational studies sampled from a broadly generalizable population may be externally valid, yet susceptible to threats to internal validity, particularly confounding. Thus, methods that address confounding and enhance transportability of study results across populations are essential for internally and externally valid causal inference, respectively. These issues persist for another problem closely related to transportability known as data-fusion. We develop a calibration method to generate balancing weights that address confounding and sampling bias, thereby enabling valid estimation of the target population average treatment effect. We compare the calibration approach to two additional doubly robust methods that estimate the effect of an intervention on an outcome within a second, possibly unrelated target population. The proposed methodologies can be extended to resolve data-fusion problems that seek to evaluate the effects of an intervention using data from two related studies sampled from different populations. A simulation study is conducted to demonstrate the advantages and similarities of the different techniques. We also test the performance of the calibration approach in a motivating real data example comparing whether the effect of biguanides vs sulfonylureas-the two most common oral diabetes medication classes for initial treatment-on all-cause mortality described in a historical cohort applies to a contemporary cohort of US Veterans with diabetes.

Association between different diabetes medication classes and risk of Parkinson's disease in people with diabetes.

PurposeDiabetes has been associated with increased risk of Parkinson's disease (PD). Diabetes medications have been suggested as a possible explanation, but findings have been inconsistent. More information on the role of exposure in different time windows is needed because PD has long onset. We assessed the association between use of different diabetes medication categories and risk of PD in different exposure periods.MethodsA case–control study restricted to people with diabetes was performed as part of nationwide register‐based Finnish study on PD (FINPARK). We included 2017 cases (diagnosed 1999–2015) with PD and 7934 controls without PD. Diabetes medication use was identified from Prescription Register (1995–2015) and categorized to insulins, biguanides, sulfonylureas, thiazolidinediones (TZDs), dipeptidyl peptidase 4 (DPP‐4) inhibitors, glucagon‐like peptide‐1 (GLP‐1) analogues and glinide. Exposure for each medication class was determined as none, at least 3 years before outcome and only within the three‐year lag time before PD outcome.ResultsThe use of insulins, biguanides, sulfonylureas, DPP‐4 inhibitors, GLP‐1 analogues or glinides was not associated with PD. Use of TZDs before lag time compared to non‐use of TZDs (adjusted odds ratio (OR) 0.78; 95% Confidence interval (CI) 0.64–0.95) was associated with decreased risk of PD.ConclusionsOur nationwide case–control study of people with diabetes found no robust evidence on the association between specific diabetes medication classes and risk of PD. Consistent with earlier studies, TZD use was associated with slightly decreased risk of PD. The mechanism for this should be verified in further studies.

Roux-en-Y gastric bypass versus best medical treatment for type 2 diabetes mellitus in adults with body mass index between 27 and 32 kg/m2: A 5-year randomized controlled trial

AimsTo evaluate the effects of Roux-en-Y gastric bypass (RYGB) versus best medical treatment in Asians with type 2 diabetes mellitus (T2DM) and class I obesity. MethodsIn this 5-year single-centre, open-label randomized controlled trial, participants were randomized to RYGB or medical treatment including newer classes of diabetes medications (ClinicalTrials.gov:NCT02041234). The primary endpoint was diabetes remission defined as HbA1c ≤ 6% (≤42 mmol/mol) and discontinuation of glucose-lowering medication at 12 months post-intervention and beyond. Glycaemia and weight changes were assessed. Continuous glucose monitoring was performed. ResultsOf 28 subjects randomized, 26 were analyzed in the final cohort (14 medical, 12 RYGB; age:44 ± 10 years, 34.6% males, BMI:29.4 ± 1.6 kg/m2). At 12 months, 50% of RYGB subjects achieved diabetes remission; 83% stopped all glucose-lowering medications. By year 5, 42% were in remission. None attained diabetes remission in the medical group. Percentage declines in fasting plasma glucose, HbA1c and BMI were significantly greater in the RYGB arm (all P < 0.05). Early improvements in glycaemic variability and time in range were similar in both treatment arms. Hypoglycaemia and surgical complications were observed in some RYGB subjects. ConclusionsOver 5 years, RYGB outperforms best medical treatment in glycemia and weight improvements for Asians with T2DM and class I obesity.

Medication Optimization Among People With Type 2 Diabetes Participating in a Continuous Glucose Monitoring-Driven Virtual Care Program: Prospective Study.

BackgroundThe Onduo virtual care program for people with type 2 diabetes (T2D) includes a mobile app, remote lifestyle coaching, connected devices, and telemedicine consultations with endocrinologists for medication management and prescription of real-time continuous glucose monitoring (RT-CGM) devices. In a previously described 4-month prospective study of this program, adults with T2D and baseline glycated hemoglobin (HbA1c) ≥8.0% to ≤12.0% experienced a mean HbA1c decrease of 1.6% with no significant increase in hypoglycemia.ObjectiveThe objective of this analysis was to evaluate medication optimization and management in the 4-month prospective T2D study.MethodsStudy participants received at least 1 telemedicine consultation with an Onduo endocrinologist for diabetes medication management and used RT-CGM intermittently to guide therapy and dosing. Medication changes were analyzed.ResultsOf 55 participants, 48 (87%) had a medication change consisting of a dose change, addition, or discontinuation. Of these, 15 (31%) participants had a net increase in number of diabetes medication classes from baseline. Mean time to first medication change for these participants was 36 days. The percentage of participants taking a glucagon-like peptide-1 receptor agonist increased from 25% (12/48) to 56% (n=27), while the percentages of participants taking a sulfonylurea or dipeptidyl peptidase 4 inhibitor decreased from 56% (n=27) to 33% (n=16) and 17% (n=8) to 6% (n=3), respectively. Prescriptions of other antidiabetic medication classes including insulin did not change significantly.ConclusionsThe Onduo virtual care program can play an important role in providing timely access to guideline-based diabetes management medications and technologies for people with T2D.Trial RegistrationClinicalTrials.gov NCT03865381; https://clinicaltrials.gov/ct2/show/NCT03865381

Racial/ethnic and socioeconomic disparities in the use of newer diabetes medications in the Look AHEAD study

SummaryBackgroundAmong patients with type 2 diabetes, minority racial/ethnic groups have a higher burden of cardiovascular disease, chronic kidney disease, and hypoglycaemia. These groups may especially benefit from newer diabetes medication classes, but high cost may limit access. We examined the association of race/ethnicity with the initiation of newer diabetes medications (GLP-1 receptor agonists, DPP-4 inhibitors, SGLT-2 inhibitors).MethodsWe conducted a secondary analysis of the Look AHEAD (Action for Health in Diabetes) trial including participants with at least one study visit after April 28, 2005. Cox proportional hazards models were used to estimate the association between race/ethnicity and socioeconomic factors with time to initiation of any newer diabetes medication from April 2005 to February 2020. Models were adjusted for demographic and clinical characteristics.FindingsAmong 4,892 participants, 63.6%, 15.7%, 12.6%, 5.2%, and 2.9% were White, Black, Hispanic, American Indian or Alaskan Native (AI/AN), or other race/ethnicity, respectively. During a median follow-up of 8.3 years, 2,180 (45.2%) participants were initiated on newer diabetes medications. Race/ethnicity was associated with newer diabetes medication initiation (p=.019). Specifically, initiation was lower among Black (HR 0.81, 95% CI 0.70 –0.94) and AI/AN participants (HR 0.51, 95% CI 0.26–0.99). Yearly family income was inversely associated with initiation of newer diabetes medications (HR 0.78, 95% CI 0.62–0.98) comparing the lowest and highest income groups. Findings were mostly driven by GLP-1 receptor agonists.InterpretationThese findings provide evidence of racial/ethnic disparities in the initiation of newer diabetes medications, independent of socioeconomic factors, which may contribute to worse health outcomes.

Glucose-Lowering Medications and Cardiovascular Outcomes.

The purpose of this review is to examine recent evidence supporting CV safety profile and improvement of CV outcomes of some of the newer classes of diabetic medications. Diabetes mellitus (DM) is associated with increased risk of cardiovascular disease (CVD). Thus, CVD management is critical in diabetic patients. Since 2008, the US Food and Drug Administration (FDA) has mandated that all newer diabetic medications should establish cardiovascular safety before it is approved for use. Diabetic medications that also lower CV risk would be a significant advancement as shown in recent studies. There are 3 new class of diabetic medications: Dipeptidyl peptidase-4 inhibitors (DPP-4), glucagon-like peptide receptor agonists (GLP-1 RA), and sodium-glucose cotransporter type 2 (SGLT 2) inhibitors which have established both CV safety and improvement in CV outcomes with some drugs. In patients with type 2 diabetes and established atherosclerotic cardiovascular disease, multiple atherosclerotic cardiovascular disease risk factors, or diabetic kidney disease, a sodium-glucose cotransporter 2 inhibitor, or a glucagon-like peptide 1 receptor agonist with demonstrated cardiovascular benefit is recommended to reduce the risk of major adverse cardiovascular events.

Role of sodium glucose cotransporter type 2 inhibitors dapagliflozin on diabetic nephropathy in rats; Inflammation, angiogenesis and apoptosis

AimsDiabetic nephropathy is a major cause of chronic kidney disease and end-stage renal failure worldwide. Dapagliflozin Sodium-glucose co-transporter 2 (SGLT2) inhibitor is a new class of diabetic medications prescribed for the treatment of type 2 diabetes. The current study investigates the possible impact of dapagliflozin (DAPA) on inflammations, apoptosis, angiogenesis and fibrosis in early-stage diabetic nephropathy using a rat model of type 2 diabetes. Main methodsRats were divided into five groups, group1: normal vehicle group, group 2: diabetic group, group 3: diabetic+ DAPA (0.75 mg/kg), group 4: diabetic+DAPA (1.5 mg/kg), group 5: diabetic+DAPA (3 mg/kg). At the end of the study, Blood glucose level was measured. Serum insulin, BUN, and SCr were measured. Insulin resistance was determined using the homeostasis model assessment for insulin resistance (HOMA-IR) index. Renal tissue homogenization was done for assessment of inflammatory markers TNF-α, PEDF, and PTX-3, In addition to apoptosis markers BCL-2 and BAX. Histopathological examinations were done for tubular renal cells and immunohistochemical examination for fibrosis marker α-SMA and angiogenic factor VEGF. Key findingsTreatments with dapagliflozin showed improvements in histopathological examinations, inflammatory and apoptotic markers compared to diabetic vehicles in a dose-dependent manner. SignificanceThus, dapagliflozin may have renoprotective effects, which be promising in diabetic patients suffered from nephropathy.

Annals for Educators - 6 October 2020.

Annals for Educators - 6 October 2020.

SGLT2 Inhibitors: Emerging Roles in the Protection Against Cardiovascular and Kidney Disease Among Diabetic Patients.

Purpose of ReviewType 2 diabetes mellitus (T2DM) is a prevalent disease with the severe clinical implications including myocardial infarction, stroke, and kidney disease. Therapies focusing on glycemic control in T2DM such as biguanides, sulfonylureas, thiazolidinediones, and insulin-based regimens have largely failed to substantially improve cardiovascular and kidney outcomes. We review the recent findings on sodium-glucose co-transporter type 2 (SGLT2) inhibitors which have shown to have beneficial cardiovascular and kidney-related effects.Recent FindingsSGLT2 inhibitors are a new class of diabetic medications that reduce the absorption of glucose in the kidney, decrease proteinuria, control blood pressure, and are associated with weight loss. SGLT2 inhibitors provide complementary therapy independent of insulin secretion or action with proved glucose-lowering effects. Recent placebo-controlled clinical trials have demonstrated that these medications can decrease cardiovascular death, progression of kidney disease, and all-cause mortality in diabetic and non-diabetic patients. Interestingly, SGT2 inhibitors such as dapagliflozin have also proven to decrease heart failure admissions and cardiovascular endpoints in non-diabetic patients, suggesting pleiotropic effects. The exact mechanisms responsible for reductions in atherosclerotic heart disease, need for kidney replacement therapy, and progressive kidney disease remain unknown. While regulation of glomerular hyperfiltration, albuminuria, and natriuresis may be part of the explanation, it is possible that complex cellular effects including energy balance optimization, downregulation of oxidative stress, and modulation of pro-inflammatory signaling pathways are associated with favorable outcomes observed in large clinical studies.ConclusionSGLT2 inhibitors are novel antidiabetic medications with immense utility in the management of patients with T2DM. Furthermore, SGLT2 inhibitors have demonstrated to reduce the progression to advanced forms of kidney disease and its associated complications. These medications should be front and center in the management of patients with diabetic kidney disease with and without chronic kidney disease as they confer protection against cardiovascular/renal death and improve all-cause mortality. Future studies should evaluate the benefits and implications of early initiation of SGLT2 inhibitors, as well as the long-term effects of this therapy.

A Randomized Encouragement Trial to Increase Mail Order Pharmacy Use and Medication Adherence in Patients with Diabetes.

Mail order pharmacy (MOP) use has been linked to improved medication adherence and health outcomes among patients with diabetes. However, no large-scale intervention studies have assessed the effect of encouraging MOP use on medication adherence. To assess an intervention to encourage MOP services to increase its use and medication adherence. Randomized encouragement trial. 63,012 diabetes patients from three health care systems: Kaiser Permanente Northern California (KPNC), Kaiser Permanente Hawaii (KPHI), and Harvard Pilgrim Health Care (HPHC) who were poorly adherent to at least one class of cardiometabolic medications and had not used MOP in the prior 12months. Patients were randomized to receive either usual care (control arm) or outreach encouraging MOP use consisting of a mailed letter, secure email message, and automated telephone call outlining the potential benefits of MOP use (intervention arm). HPHC intervention patients received the letter only. We compared the percentages of patients that began using MOP and that became adherent to cardiometabolic medication classes during a 12-month follow-up period. We also conducted a race/ethnicity-stratified analysis. During follow-up, 10.6% of intervention patients began using MOP vs. 9.3% of controls (p < 0.01); the percent of cardiometabolic medication delivered via mail was 42.1% vs. 39.8% (p < 0.01). Metformin adherence improved in the intervention arm relative to control at the two KP sites (52% vs. 49%, p < 0.01). Stratified analyses suggested a significant positive effect of the intervention in White (RR: 1.12, 95% CI: 1.03, 1.22) and Asian (RR: 1.30, 95% CI: 1.17, 1.45) patients. This pragmatic trial showed that simple outreach to encourage MOP modestly increased its use and improved adherence measured by refills to a key class of diabetes medications in some settings. Given its minimal cost, clinicians and health systems should consider outreach interventions to actively promote MOP use among diabetes patients. ClinicalTrials.gov registration number: NCT02621476.

37-OR: Racial and Socioeconomic Disparities in the Use of Newer Classes of Diabetes Medications

Among patients with type 2 diabetes (T2D), racial/ethnic minorities and those of lower socioeconomic status (SES) have a higher burden of coronary artery disease, chronic kidney disease, and hypoglycemia. Therefore, these groups may especially benefit from newer diabetes medication classes (GLP-1 receptor agonists, DPP-4 inhibitors, SGLT2 inhibitors), but high cost may limit access. We conducted a secondary analysis of the Look AHEAD (Action for Health in Diabetes) randomized trial to assess the associations of race/ethnicity and SES with newer diabetes medication use. Look AHEAD compared an intensive lifestyle intervention to diabetes support and education among U.S. adults with obesity and T2D enrolled from 2001-2004. Medications, all prescribed outside of the study, were ascertained yearly. We used Cox proportional hazards models to estimate the association between self-reported race/ethnicity and SES factors and time to initiation of any newer diabetes medication through October 2019, adjusted for time-varying HbA1c, BMI, and number/type of diabetes medications; and baseline study arm, demographics, and comorbidities; fully-adjusted results are presented. Of 4,892 participants, 64%, 16%, 13%, and 8% were white, black, Hispanic, and other race/ethnicities, respectively. Over a median follow-up of 8.3 years, 44% initiated a newer diabetes medication. Black race was associated with significantly lower initiation of newer medications compared to whites (HR 0.81; 95% CI 0.80-0.94); there was no difference by other race/ethnic group. Yearly family income was inversely associated with the outcome: HR 0.69 (95% CI 0.55-0.87) comparing the lowest vs. the highest income group. Education, employment, and health insurance were not significantly associated with the outcome. These findings provide evidence of racial and SES disparities in use of newer diabetes medications, independent of glycemic control, that may impede access to these drugs for the individuals who need them most. Disclosure A. Elhussein: None. M. Bancks: None. W.C. Knowler: None. A.L. Peters: Advisory Panel; Self; Abbott, Bigfoot Biomedical, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, MannKind Corporation, Medscape, Novo Nordisk Inc., Sanofi US. Consultant; Self; Livongo Health. Research Support; Self; Dexcom, Inc., vTv Therapeutics. Other Relationship; Self; Livongo Health, Mellitus Health, Omada Health, Stability Healthcare, Whole Biome Inc. E.M. Vaughan: None. N.M. Maruthur: Other Relationship; Self; Johns Hopkins HealthCare Solutions. J. Clark: None. S.J. Pilla: None. Funding National Institute of Diabetes and Digestive and Kidney Diseases (U01DK057149)

Dapagliflozin, a sodium glucose cotransporter 2 inhibitors, protects cardiovascular function in type-2 diabetic murine model

Diabetes mellitus and its complications are major international health problems in which there are many limitations to the orthodox approaches in the treatment. Sodium glucose cotransporter 2 (SGLT2) inhibitors are a new class of diabetic medications, with a different mechanism of action that may reduce risk of cardiovascular complications. To evaluate the effect of SGLT2 inhibitor monotherapy on cardiovascular complications in patients with type-2 diabetes and to compare its effect with the first-line therapy, metformin. Eighty rats divided into four groups were used: nondiabetic, diabetic nontreated, diabetic + met and diabetic + dapa. At the end, the arterial blood pressure and cardiac performance were assessed. Glycemic index, lipid profile, total antioxidant capacity, malondialdehyde, tumour necrosis factor a were measured. DNA changes were assessed from the hearts and aortae. Aortic tissue changes recorded using haematoxylin and eosin, Masson trichrome and iNOS immune stain. Glycemic index, lipid profile, oxidative stress and inflammatory parameters were significantly improved in both metformin and dapagliflozin treated groups with significant improvement in blood pressure and cardiac performance. Also, there were noticeable significant reduction in DNA fragmentation in aortic and cardiac tissues and reduction in collagen deposition and iNOS expression in aortic tissue. Dapagliflozin treatment results' significantly surpassed improvement of metformin treatment nearly in all parameters. Total genomic DNA extraction proved that SGL2 inhibitor (dapagliflozin) has superior glycemic control and cardiovascular protective effect over metformin especially in type-2 diabetes with high fat intake.

Effect of Insulin Sensitizers and Sodium Glucose Cotransporter 2 Inhibitor on Glycemic State and Cardiovascular Performance in Type II Diabetic Rats

Abstract Background Cardiovascular disease is the most life-threatening diabetic complication. Type II diabetes may lead to damage of the heart muscle. Sodium glucose cotransporter 2 (SGL2) inhibitors are a new class of diabetic medications indicated only for the treatment of type II diabetes. Aim This investigation was assigned to compare the effect of metformin and SGL2 inhibitors (dapaglifilizone) in type II diabetic rats. Design and methods: Eighty rats divided into four groups were used: non diabetic; diabetic; diabetic metformin -treated; diabetic dapagliflizoline- treated. At the end, arterial blood pressure and cardiac performance (cardiac contractility and heart rate) were assessed. Serum glucose, glycosylated hemoglobin (HbA1c), insulin, lipid profile, total antioxidant capacity, malondialdehyde, tumor necrosis factor α were measured. HOMA-IR index was calculated. DNA changes were assessed from hearts and aortea. Aortic endothelial changes recorded using H&amp;E and masson trichome techniques. Results Glycemic index, lipid profile, oxidative stress and inflammatory parameters were significantly improved in both metformin and dapagliflizoline treated groups with also significant improvement in blood pressure, Cardiac performance and reduction in collagen deposition in aortic tissue and DNA fragmentation. Dapagliflizoline treatment results were significantly improved in all parameters compared to metformin treatment. Conclusion SGL2 inhibitors (dapaglifilizone) successfully restored glycemic state, cardiac performance, DNA and endothelial changes in type II diabetic rats compared to metformin.

Prescription patterns of diabetes medications influencing clinical outcomes of heart failure patients with reduced ejection fraction.

AimsWe collected the different prescription patterns of diabetes medications in a cohort of patients with heart failure with reduced ejection fraction (HFrEF) and analysed the impact of different prescription patterns on clinical outcomes.Methods and resultsConsecutive diabetic patients with HFrEF from a heart failure referral centre were retrospectively analysed between 2015 and 2016. Exclusion criteria include being lost to follow‐up, not receiving diabetes medications, and having severe renal impairment with a glomerular filtration rate < 30 mL/min/1.73 m2. Prescription of diabetes medications and the respective clinical outcomes were collected between 2016 and 2018. Among 381 patients (mean age, 64.8 ± 12.8 years; 71.9% male; mean left ventricular ejection fraction, 27.6 ± 7.0%; mean body mass index, 26.1 ± 4.7 kg/m2), the prescription rates of sodium‐glucose co‐transporter 2 inhibitor (SGLT2i) increased from 10.3% in 2016 to 17.6% in 2017 and 26.5% in 2018 (P < 0.001); the prescription rates of metformin, sulfonylurea, insulin, and dipeptidyl peptidase‐4 inhibitors did not change significantly over time. The prescription rates of metformin and SGLT2i were significantly higher in patients managed by cardiologists than non‐cardiologists (in 2018, 71.1% vs. 44.2% for metformin, 45.4% vs. 9.9% for SGLT2i, both P < 0.001). During the study period, annualized event rates of cardiovascular death or first unplanned HF hospitalization were 19.0 per 100 patient‐years. After a multivariate analysis, prescriptions of metformin {odds ratio (OR): 0.49 [95% confidence interval (CI) 0.27–0.51], P < 0.001} and SGLT2i [OR: 0.52 (95% CI 0.28–0.98), P = 0.042] were independently associated with lower annualized event rates of cardiovascular death or unplanned HF hospitalization.ConclusionsPrescription patterns of diabetes medications in diabetics with HFrEF were diverse among different specialists. Prescriptions of metformin and SGLT2i were associated with favourable clinical outcomes. Our finding indicates the importance of awareness of beneficial effect of different classes of diabetes medications and collaboration between specialists in the management of diabetic HFrEF patients.