Use Of SGLT2i Research Articles

Hormonal, Metabolic and Hemodynamic Adaptations to Glycosuria in Type 2 Diabetes Patients Treated with Sodium-Glucose Co-Transporter Inhibitors.

The advent of the sodium-glucose cotransporter-2 inhibitors [SGLT-2i] provides an additional tool to combat diabetes and complications. The use of SGLT-2i leads to effective and durable glycemic control with important reductions in body weight/fat and blood pressure. These agents may delay beta-cell deterioration and improve tissue insulin sensitivity, which might slow the progression of the disease. In response to glycosuria, a compensatory rise in endogenous glucose production, sustained by a decrease in plasma insulin with an increase in glucagon has been described. Other possible mediators have been implicated and preliminary findings suggest that a sympathoadrenal discharge and/or rapid elevation in circulating substrates (i.e., fatty acids) or some yet unidentified humoral factors may have a role in a renal-hepatic inter-organ relationship. A possible contribution of enhanced renal gluconeogenesis to glucose entry into the systemic circulation has not yet been ruled out. Additionally, tissue glucose utilization decreases, whereas adipose tissue lipolysis is stimulated and, there is a switch to lipid oxidation with the formation of ketone bodies; the risk for keto-acidosis may limit the use of SGLT-2i. These metabolic adaptations are part of a counter-regulatory response to avoid hypoglycemia and, as a result, limit the SGLT-2i therapeutic efficacy. Recent trials revealed important cardiovascular [CV] beneficial effects of SGLT-2i drugs when used in T2DM patients with CV disease. Although the underlying mechanisms are not fully understood, there appears to be "class effect". Changes in hemodynamics and electrolyte/body fluid distribution are likely involved, but there is no evidence for anti-atherosclerotic effects. It is anticipated that, by providing durable diabetes control and reducing CV morbidity and mortality, the SGLT-2i class of drugs is destined to become a priority choice in diabetes management.

1247-P: Anticipating the Impact of 2019 Guidelines: Use of SGLT2i and GLP-1RA in Patients with Diabetes and Cardiovascular Disease

Objective: To describe use of GLP-1 RA and SGLT2i in the treatment of patients with diabetes and cardiovascular disease (CVD) using a large, clinical database. Study Design: A retrospective descriptive analysis in a clinical database with 22 million longitudinal patient records across 22 health care organizations (HCOs). Population Studied: A total of 2.6 million patients aged 18-75 with ≥ 2 ambulatory visits with primary care, endocrinology, cardiology, or nephrology in the past 18 months were included from 1/2013 to 3/2018. A subset of 350,000 patients with a type 2 diabetes (DM) diagnosis was observed during the 36 months ending 2016 Q1, 2017 Q1, 2018 Q1 for existing or new prescriptions of novel antidiabetic agents: GLP-1, SGLT2, or DPP-4. Patients were stratified by presence of cardiovascular disease (CVD), baseline DM medication regimen, and HbA1c ≥ 8.0, indicating need for advancing therapy. Principal Findings: In 2018 Q1, the prevalence of CVD among patients with type 2 DM was 31%. Among patients with type 2 DM, a baseline oral antidiabetic regimen, and HbA1c ≥ 8.0, those with CVD were more likely to have any new DM medication class added (51% vs. 44%, p < 0.001), but no more likely than those without CVD to have a GLP-1 or SGLT2 added (p = 0.70). Patients with CVD were more likely to be prescribed insulin than those without evidence of CVD (20.2% vs. 10.3%, p < 0.001). From the 3-year period ending 2016 Q1 to that ending 2018 Q1, GLP-1 and SGLT2 prescriptions increased 3% and 4%, respectively, among all patients with type 2 DM. Conclusions: Overall prescriptions of GLP-1 and SGLT2 are increasing but represent only 12% and 13%, respectively, of prescriptions for patients with type 2 DM (vs. 20% for DPP-4). Among patients with type 2 DM, these agents were prescribed no more frequently to those with established CVD than to those without CVD. Prescribing behavior complied with the new guidelines in only 14% of patients with both type 2 diabetes and CVD (range 8-31% across 20 HCOs). Disclosure C.R. Rattelman: None. E.L. Ciemins: None. J.K. Cuddeback: None. Funding Novo Nordisk

2352-PUB: Level of Glycemic Control in Type 2 Diabetes (T2D) Patients with Established Cardiovascular Disease (eCVD) or Chronic Kidney Disease (CKD) Prescribed an SGLT2i

The recent ADA/EASD consensus statement for management of hyperglycemia preferentially recommends the use of SGLT2i in patients with eCVD or CKD. However, no specific data exist on the level of glycemic control in this high-risk population currently receiving SGLT2i. Our study assessed glycemic control among adult T2D patients with eCVD/CKD on dual therapy (metformin+SGLT2i) at 3 different HbA1c targets (≥7%, ≥7.5%, ≥8%) using the GE Centricity Electronic Medical Record database (June 2015-June 2018). The index date was the most recent encounter for metformin+SGLT2i users. Patients were required to have ≥1 HbA1c measure in the 12 months prior to the index date and ≥1 year of medical history available. ECVD/CKD included patients with CVD only, CKD only, or both CVD and CKD. Results were examined in the overall study cohort and by subgroups of age, gender, and race. Of the 987 included study patients, 40% were female, median age was 62 years, and median A1c was 7.5%. Table 1 shows the level of glycemic control among the study population. 68%, 52% and 36% of patients had HbA1c ≥7%, ≥7.5%, and ≥8%, respectively. In conclusion, many patients with eCVD/CKD on dual therapy of metformin and SGLT2i were observed to have inadequate glycemic control and should be evaluated for medication adherence and further pharmacological intensification if appropriate. Disclosure K. Iglay: Employee; Self; Merck & Co., Inc. Stock/Shareholder; Self; Merck & Co., Inc. N. Bansal: Consultant; Self; Merck & Co., Inc. T. Gulati: Consultant; Self; Merck & Co., Inc. H. Hannachi: Employee; Self; Merck & Co., Inc. G. Fernandes: None. S. Rajpathak: None.

CVOTs applicability on SGLT-2i in a real world population of type 2 diabetes patients

OBJECTIVE OF THE STUDY To evaluate the generalizability of the results of recent CVOTs on SGLT2i (EMPA-REG OUTCOMES, CANVAS, DECLARE-TIMI 58 and VERTIS-CV) in patients with T2DM in the real world. DESIGN AND METHODS Database of AMD Annals 2018 was used in this study, including all patients cared for by 222 diabetes centers during 2016. Starting from the eligibility criteria adopted in the different trials, the analysis aimed to identify the subjects potentially eligible for each trial, compare their characteristics with those of the population recruited in the trials, and evaluate the current use of these drugs among the potentially eligible patients registered in AMD Annals database. RESULTS The evaluable cases (i.e. presence of information on all eligibility criteria) ranged from 149.064 for the CANVAS to the 342.205 subjects for the EMPAREG-OUTCOME. Overall, the eligible patients in AMD Annals ranged from 40,039 for the EMPAREG OUTCOME study (11.7%) to 144,166 (55.9%) for DECLARE-TIMI 58. The percentage of patients actually treated ranged from 4.4% (6.373) for DECLARE-TIMI 58 to 6.6% (2.917) for CANVAS. As compared to RCTs’ populations, AMD Annals population was older, included a larger proportion of women, showed slightly lower BMI and better metabolic control, and longer diabetes duration. Prevalence of major cardio-cerebrovascular events was lower, while the percentage of subjects with peripheral vasculopathy was higher; the proportion of subjects with reduced glomerular filtrate or albuminuria and diabetic retinopathy was higher. CONCLUSIONS The generalizability of CVOTs’ results to the real world patients is only partial, because the populations are quite different. A very low clinical use of SGLT-2i is documented. This is at least in part due to the strict AIFA criteria for reimbursement, which reduce the proportion of patients who could benefit from treatment with SGLT2i on major cardiovascular events and mortality; however, an identical advantage of the treatment obtained in RCTs cannot be hypothesized in the AMD Annals population. KEY WORDS type 2 diabetes; CVOT; real world; generalizability; SGLT2i

Risk of fracture with dipeptidyl peptidase-4 inhibitors, glucagon-like peptide-1 receptor agonists, or sodium-glucose cotransporter-2 inhibitors in real-world use: systematic review and meta-analysis of observational studies.

Cumulative evidence from randomized control trials (RCTs) with limited fracture events showed that the use of DPP-4i, GLP-1ra, or SGLT2i may not affect the risk of fracture. However, additional insights from large population-based studies with routinely collected data on fracture events and an adequate amount of fracture events are necessary to draw firm conclusions. To refine and complement the results from RCTs, a systematic review and meta-analysis of observational studies were performed to investigate the association between the use of DPP-4i, GLP-1ra, or SGLT2i and the risk of fracture in real-world settings. The PubMed and Web of Science databases were searched to identify relevant observational studies. A random-effect model was used to estimate the summary relative risks (RRs). The use of DPP-4i (RR 0.83, 95% CI [confidence interval] 0.60, 1.14; n = 11), GLP-1ra (RR 0.65, 95% CI 0.24, 1.74; n = 4), or SGLT2i (RR 1.02, 95% CI 0.91, 1.16; n = 4) was not associated with the risk of fracture. In general, there was a consistent lack of association between the use of DPP-4i or GLP-1ra and the risk of fracture across nearly all subgroups, except for a significantly reduced risk of hip fracture with the use of GLP-1ra (RR 0.21, 95% CI 0.04, 0.98). Cumulative real-world evidence does not support an association between the use of DPP-4i, GLP-1ra, or SGLT2i and the risk of fracture. Our findings, together with the cumulative evidence from RCTs, should reassure policy makers and medical practitioners that the use of these medications is unlikely to increase the risk of fracture among type 2 diabetes mellitus patients in general. Further studies need to investigate the long-term impact of these drugs on the fracture risk, particularly in high-risk populations.

Prospective study of prescribing pattern in patients with T2DM and hypertension

Rational drug utilization must be promoted in patients with type 2 diabetes mellitus (T2DM) as it is emerging as one of the major health related issue leading to increase in rate of morbidity and mortality. The present study was a drug utilization study which was done to assess the prescribing pattern of antidiabetic drugs in patients with diabetes with or without hypertension. In present prospective study, a total 75 patients were studied in the Department of Medicine, Mayo Institute of Medical sciences, Barabanki from January 2016 to May 2016. The history and the details about the prescription medicine were recorded. In present study all were T2DM patients; out of that 26.66% were having only diabetes whereas 73.33% were having diabetes with hypertension. The most commonly prescribed drug was metformin (95%) followed by glimepiride (80%) and gliptins (70%).In present study insulin was the least used drug. Triple drug therapy (40%) was most common followed by dual therapy (29.33%). Use of SGLT2i was more in patients with hypertension as compared to patients with diabetes only (p=0.0006).Telmisartan (67.27%) was the most commonly used antihypertensive drug. Still, among physician OHAs are the drug of choice for the treatment of T2DM, and metformin was the most commonly prescribed drug followed by glimepiride. For hypertension ARB was the preferred choice in diabetics.