scholarly journals FRAILTY AND THE EFFECTIVENESS AND SAFETY OF NEW GLUCOSE-LOWERING DRUGS IN OLDER ADULTS WITH TYPE 2 DIABETES

2019 ◽  
Vol 3 (Supplement_1) ◽  
pp. S581-S581
Author(s):  
Dae H Kim ◽  
Elisabetta Patorno ◽  
Medha Munshi
Keyword(s):  
Type 2 Diabetes ◽  
Older Adults ◽  
Clinical Trials ◽  
Frailty Index ◽  
Emergency Department Visits ◽  
Care Providers ◽  
Glucose Lowering ◽  
Medicare Data ◽  
Dipeptidyl Peptidase 4 Inhibitors

Abstract Recently, several classes of non-insulin glucose-lowering drugs, such as dipeptidyl peptidase-4 inhibitors (DPP4i), glucagon-like peptide-1 receptor agonists (GLP1-RA), and sodium glucose co-transporter-2 inhibitors (SGLT2i), have been approved to treat type 2 diabetes. Clinical trials have shown that GLP1RA and SGLT2i confer cardiovascular benefit, while DPP4i do not have such benefit; these drugs do not seem to increase the risk of hypoglycemia. However, due to underrepresentation of older adults with frailty and lack of frailty assessment in clinical trials, little is known about how the effectiveness and safety of these drugs change across different levels of frailty. In this symposium, we present the real-world evidence from Medicare data April 2013-December 2016 on the utilization trends of newly approved diabetes drugs (Dr. Dave) and comparative effectiveness and safety of SGLT2i vs sulfonylurea (Dr. Pawar), SGLT2i vs DPP4i (Dr. Kim), and SGLT2i vs GLP1-RA (Dr. Patorno). The outcomes were 1) composite cardiovascular endpoint of mortality, myocardial infarction, stroke, or heart failure; and 2) severe hypoglycemia, defined as emergency department visits or hospitalizations due to hypoglycemia. We applied a validated claims-based frailty index (CFI) to estimate the treatment effectiveness and safety in non-frail (CFI<0.10), pre-frail (CFI 0.10-0.19), or frail individuals (CFI≥0.20). Following individual presentations, Dr. Munshi and presenters will lead an interactive discussion about clinical implications and methodological challenges in conducting geriatric pharmacoepidemiologic studies using Medicare data. This symposium will demonstrate the utility of CFI in claims-based pharmacoepidemiologic studies and provide health care providers with new evidence to tailor diabetes pharmacotherapy based on frailty.

scholarly journals FRAILTY AND THE COMPARATIVE EFFECTIVENESS AND SAFETY OF SGLT2I AND SULFONYLUREA IN OLDER ADULTS WITH TYPE 2 DIABETES

2019 ◽  
Vol 3 (Supplement_1) ◽  
pp. S581-S581
Author(s):  
Ajinkya Pawar ◽  
elisabetta Patorno ◽  
Dae Kim
Keyword(s):  
Type 2 Diabetes ◽  
Older Adults ◽  
Cohort Study ◽  
Comparative Effectiveness ◽  
Retrospective Cohort ◽  
Severe Hypoglycemia ◽  
Medicare Data ◽  
Cardiovascular Endpoint

Abstract We conducted a 1:1 propensity score-matched retrospective cohort study of 70,826 patients with type 2 diabetes (mean age, 71.4 years [standard deviation, 5.0]) initiating a SGLT2i or a second-generation sulfonylurea in Medicare data. We estimated HRs (95% CIs) for a composite cardiovascular endpoint and severe hypoglycemia comparing the two treatments in the entire population and by the CFI-based frailty subgroups. Compared with sulfonylureas, SGLT2is were associated with lower rates of the composite cardiovascular endpoint (HR, 0.68 [95% CI, 0.62-0.75]) and severe hypoglycemia (0.43 [0.35-0.53]) over a mean follow-up of 9.5 months. The lower rate of composite cardiovascular endpoint for SGLT2i vs sulfonylureas was observed in pre-frail (0.68 [0.61-0.77]) and frail (0.64 [0.53-0.77]) subgroups, but not in non-frail subgroup (0.95 [0.59-1.54]). The rate of severe hypoglycemia was consistently lower for SGLT2i vs sulfonylureas across frailty subgroups (non-frail, 0.37 [0.12-1.16]; pre-frail, 0.45 [0.35-0.59]; frail, 0.40 [0.28-0.58]).

scholarly journals Decrease of cardiovascular risk in patients with type 2 diabetes: review of the common strategies and clinical studies

2018 ◽  
Vol 21 (3) ◽  
pp. 193-205 ◽  
Author(s):  
Vladimir V. Salukhov ◽  
Yurii Sh. Khalimov ◽  
Sergey B. Shustov ◽  
Dmitriy V. Kadin
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Cardiovascular Disease ◽  
Clinical Trials ◽  
Lifestyle Changes ◽  
Cardiovascular Outcome ◽  
Cardiovascular Risks ◽  
Glucose Lowering ◽  
Lowering Effect

Military Medical Academy of S.M. Kirov, Saint-Petersburg, Russia Recent clinical trials about the cardiovascular safety of empagliflozin and liraglutide demonstrated a convincing lowering effect on mortality from cardiovascular causes among the patients with type 2 diabetes. These findings resulted in many questions about why this phenomenon was seen in two drugs with widely different mechanisms of functioning. It is important to note that the glucose-lowering effect was moderate, although a feature seen in both empagliflozin and liraglutide was their ability to increase insulin sensitivity. In many fundamental studies, this feature was associated with a reduction of cardiovascular risks. Insulin resistance, which has always been a pathophysiological base for the development of cardiovascular disease in patients with type 2 diabetes, is a topic for this report. Different methods to manage insulin resistance, including lifestyle changes, drug treatment and metabolic surgery, are discussed. Furthermore, the most common features of glucose-lowering drugs are analysed, including protective effects for cardiovascular outcomes in patients with type 2 diabetes presented in randomised clinical trials. Studies include the United Kingdom Prospective Diabetes Study (UKPDS), PROspective pioglitAzone Clinical Trial In macroVascular Events (PROactive), Insulin Resistance Intervention After Stroke (IRIS), Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results (LEADER) and the Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients (EMPA-REG OUTCOME). The current study shows that the potential to reduce the risk of cardiovascular disease is determined not only by effective lowering of glucose but also by the ability to lower insulin resistance, which causes a paradigm shift in the management of type 2 diabetes.

scholarly journals Incorporating SGLT2i and GLP-1RA for Cardiovascular and Kidney Disease Risk Reduction: Call for Action to the Cardiology Community

Circulation ◽  
2021 ◽  
Vol 144 (1) ◽  
pp. 74-84
Author(s):  
Adam J. Nelson ◽  
Neha J. Pagidipati ◽  
Vanita R. Aroda ◽  
Matthew A. Cavender ◽  
Jennifer B. Green ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Kidney Disease ◽  
Disease Risk ◽  
Primary Care Providers ◽  
Care Providers ◽  
Glucose Lowering ◽  
Sodium Glucose Cotransporter ◽  
Glucagon Like Peptide 1 ◽  
Risk Reducing

Multiple sodium glucose cotransporter-2 inhibitors (SGLT-2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA) have been shown to impart significant cardiovascular and kidney benefits, but are underused in clinical practice. Both SGLT-2i and GLP-1RA were first studied as glucose-lowering drugs, which may have impeded uptake by cardiologists in the wake of proven cardiovascular efficacy. Their significant effect on cardiovascular and kidney outcomes, which are largely independent of glucose-lowering effects, must drive a broader use of these drugs. Cardiologists are 3 times more likely than endocrinologists to see patients with both type 2 diabetes and cardiovascular disease, thus they are ideally positioned to share responsibility for SGLT-2i and GLP-1RA treatment with primary care providers. In order to increase adoption, SGLT-2i and GLP-1RA must be reframed as primarily cardiovascular and kidney disease risk-reducing agents with a side effect of glucose-lowering. Coordinated and multifaceted interventions engaging clinicians, patients, payers, professional societies, and health systems must be implemented to incentivize the adoption of these medications as part of routine cardiovascular and kidney care. Greater use of SGLT-2i and GLP-1RA will improve outcomes for patients with type 2 diabetes at high risk for cardiovascular and kidney disease.

Sulfonylureas in today’s blood glucose lowering therapy.New data on advantages and potential barriers of an “old” antidiabetic group

2015 ◽  
Vol 156 (13) ◽  
pp. 511-515
Author(s):  
Gábor Winkler
Keyword(s):  
Type 2 Diabetes ◽  
Blood Glucose ◽  
Glucose Lowering ◽  
Dipeptidyl Peptidase 4 ◽  
Sulfonylurea Compounds ◽  
Drug Of Choice ◽  
Antidiabetic Treatment ◽  
Dipeptidyl Peptidase 4 Inhibitors ◽  
Glucose Lowering Therapy

Sulfonylurea compounds have been basic elements of antidiabetic treatment in type 2 diabetes for a long time. However, with the introduction of incretin type insulin secretagogues it is often arises, whether is still there a place for sulfonylureas in the today’s therapy. To answer this question the author overviews general pharmaceutical characteristics of the sulfonylurea compounds as well as individual particularities of the second generation derivatives used at present in Hungary. The author details also the most important differences between incretin type drugs − first of all dipeptidyl peptidase-4 inhibitors − and sulfonylureas. On the basis of available data it can be concluded in accordance with the latest international guidelines, that sulfonylureas have still role in the blood glucose lowering therapy of type 2 diabetes, though they became somewhat pushed back among insulin secretagogue type drugs. If a sulfonylurea compound is the drug of choice, it is important to select the appropriate molecule (in case of normal renal function gliclazide or glimepiride). It is also important to re-educate the patient, as well as to apply the minimal dose providing the desired glycaemic effect. Orv. Hetil., 2015, 156(13), 511–515.

Exclusion of Older Adults from Ongoing Clinical Trials About Type 2 Diabetes Mellitus

2013 ◽  
Vol 61 (5) ◽  
pp. 734-738 ◽  
Author(s):  
Alfonso J. Cruz-Jentoft ◽  
Marina Carpena-Ruiz ◽  
Beatriz Montero-Errasquín ◽  
Carmen Sánchez-Castellano ◽  
Elisabet Sánchez-García
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Older Adults ◽  
Clinical Trials ◽  
Type 2 Diabetes Mellitus

Cardiovascular Outcomes Trials in Type 2 Diabetes Mellitus

Cardiology ◽  
2016 ◽  
Vol 135 (2) ◽  
pp. 108-126
Author(s):  
Karan Kapoor ◽  
Praveen George ◽  
Michael Miller
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Disease Risk ◽  
Macrovascular Disease ◽  
Cardiovascular Outcomes ◽  
Significant Shift ◽  
Glucose Lowering ◽  
Dipeptidyl Peptidase 4 Inhibitors

Objectives: To review the spectrum of contemporary cardiovascular outcomes trials (CVOTS) in type 2 diabetes mellitus (T2DM), spanning both the pre- and post-ACCORD eras. Methods: We reviewed a total of 12 CVOTs and delineated the two eras in accordance with the 2008 US Food and Drug Administration (FDA) mandate requiring completion of CVOTs prior the licensing of new glucose-lowering agents. The salient implications regarding macrovascular disease complications were summarized. Results: Five trials in the pre-ACCORD and 7 in the post-ACCORD era were identified. Heterogeneous results pertaining to the degree of glycemic control associated with optimal macrovascular disease risk reduction, as well as the safest pharmacologic means to do so, were observed. Conclusions: The post-ACCORD era is representative of a significant shift in the landscape of CVOTs in T2DM, with an emphasis on safety of glucose-lowering agents. Recently completed and ongoing trials of dipeptidyl peptidase-4 inhibitors and sodium-glucose cotransporter 2 inhibitors will continue to inform clinical practice on safe and effective ways to reduce CV risk in T2DM.

scholarly journals FRAILTY AND THE COMPARATIVE EFFECTIVENESS AND SAFETY OF SGLT2I AND DPP4I IN OLDER ADULTS WITH TYPE 2 DIABETES

2019 ◽  
Vol 3 (Supplement_1) ◽  
pp. S582-S582
Author(s):  
Dae H Kim ◽  
Ajinkya Pawar ◽  
Seoyoung Kim ◽  
Elisabetta Patorno
Keyword(s):  
Type 2 Diabetes ◽  
Older Adults ◽  
Comparative Effectiveness ◽  
Retrospective Cohort ◽  
Severe Hypoglycemia ◽  
Similar Rate ◽  
Medicare Data ◽  
Cardiovascular Endpoint

Abstract We conducted a 1:1 propensity score-matched retrospective cohort study of 83,432 patients with type 2 diabetes (mean age, 71.5 years [standard deviation, 5.0]) initiating a SGLT2i or a DPP4i in Medicare data. We estimated HRs (95% CIs) for a composite cardiovascular endpoint and severe hypoglycemia comparing the two treatments in the entire population and by the CFI-based frailty subgroups. Compared with DPP4i, SGLT2i were associated with a lower rate of the composite cardiovascular endpoint (HR, 0.70 [95% CI, 0.64-0.77]) and a similar rate of severe hypoglycemia (0.88 [0.71-1.07]) over a mean follow-up of 8.8 months. The rate of composite cardiovascular endpoint for SGLT2i vs DPP4i was consistently lower in pre-frail (0.71 [0.64-0.79]) and frail (0.67 [0.55-0.80]) subjects, but not in non-frail patients (0.98 [0.62-1.54]). The rate of severe hypoglycemia was not meaningfully different between SGLT2i and DPP4i (non-frail, 0.39 [0.12-1.16]; pre-frail, 0.83 [0.65-1.07]; frail, 1.13 [0.78-1.64]).

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