sitagliptin-phosphate and Stroke

Patients with type 2 diabetes mellitus (T2DM) have a very high risk of cardiovascular related events, and reducing complications is an important evaluation criterion of efficacy and safety of hypoglycemic drugs. Previous studies have shown that the dipeptidyl peptidase-4 (DPP-4) inhibitors (DPP4i), such as sitagliptin, might reduce the incidence of major cardiovascular events (MACEs). However, the safety and efficacy of sitagliptin remains controversial, especially the safety for cardiovascular related events. Here, a systematic review was conducted to assess the cardiovascular safety of sitagliptin in T2DM patients. The literature research dating up to October 2018 was performed in the electronic database. The clinical trials about sitagliptin for T2DM patients were included. Two reviewers independently screened literature according to the inclusion and exclusion criteria. The primary outcome was the MACE, and the secondary outcome was all-cause mortality. Finally, 32 clinical trials composed of 16082 T2DM patients were included in this meta-analysis. The results showed that: there was no significant difference between sitagliptin group and the control group on MACE (odds ratio (OR) = 0.85, 95% confidence intervals (CIs) = 0.63-1.15), myocardial infarction (MI) (OR = 0.66, 95% CI = 0.38-1.16), stroke (OR = 0.83, 95% CI = 0.44-1.54) and mortality (OR = 0.52, 95% CI = 0.26-1.07). These results demonstrated that sitagliptin did not increase the risk of cardiovascular events in patients with T2DM.

Topics: Cardiovascular Abnormalities; Diabetes Mellitus, Type 2; Female; Humans; Hypoglycemic Agents; Male; Myocardial Infarction; Risk Factors; Sitagliptin Phosphate; Stroke

Impaired glucose tolerance (IGT) is highly prevalent after stroke and is associated with recurrent stroke and unfavourable outcome.. We aimed to assess the feasibility, safety and effects on glucose metabolism of metformin or sitagliptin in patients with transient ischaemic attack (TIA) or minor ischaemic stroke and IGT.. We performed a multicentre, randomised, controlled, open-label phase II trial with blinded outcome assessment.. Patients were randomised in a 2:1:1 ratio to 'no medication', sitagliptin or metformin.. Primary outcome measures were baseline adjusted differences of 2-hour postload glucose; secondary outcome measures fasting glucose, glycosylated haemoglobin 1c (HbA1c) levels, tolerability and safety of metformin and sitagliptin at 6 months. Patients on metformin or sitagliptin were contacted by telephone for recording of possible adverse events and to support continuation of treatment at 2 weeks, 6 weeks and 3 months after inclusion. These events were not analysed as outcome measures.. Fifty-three patients were randomised to control group, 26 to metformin and 22 to sitagliptin. We found no significant differences in 2-hour postload glucose between patients on antidiabetic drugs and controls ((-0.04 mmol/L (95% CI -0.53 to 0.45)). Patients in the treatment arms had reduced fasting glucose: ((-0.21 mmol/L (95% CI -0.36 to -0.06)) and HbA1c levels ((-1.16 mmol/mol (95% CI -1.84 to -0.49)). Thirteen patients (50%) on metformin and 7 (32%) on sitagliptin experienced side effects. Sixteen patients (61%) in the metformin and 13 (59%) in the sitagliptin group were still on treatment after 6 months.. Metformin and sitagliptin were both effective in reducing fasting glucose and HbA1c levels in patients with recent TIA or minor ischaemic stroke and IGT. However, the reduction of glucose levels and sample size was relatively small. The clinical relevance, therefore, needs to be tempered. A phase III trial is needed to investigate whether medical treatment, compared with lifestyle intervention or a combination of both, not only improves glucose metabolism in IGT, but also leads to reduction of recurrent TIA or ischaemic stroke in these patients.. NL3048.

Topics: Blood Glucose; Brain Ischemia; Diabetes Mellitus, Type 2; Double-Blind Method; Drug Therapy, Combination; Feasibility Studies; Glucose Intolerance; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Ischemic Attack, Transient; Ischemic Stroke; Metformin; Sitagliptin Phosphate; Stroke; Treatment Outcome

Type 2 diabetes (T2D) patients are at increased risk for cardiovascular (CV) events. Most guidelines recommend treating low-density lipoprotein cholesterol (LDL-C) levels to ≤70 mg/dL (1.8 mM) for patients with T2D and established atherosclerotic CV disease, and some a more aggressive target of ≤55 mg/dL (1.4 mM). Our objective was to assess the degree to which these LDL-C targets are achieved in routine practice.. Using data from TECOS, an international pragmatic CV outcomes trial of sitagliptin vs placebo, we assessed lipid-lowering treatment among patients with T2D and CV disease, baseline lipid values, and the association between baseline LDL-C and 5-year risk for major adverse cardiac events (MACE; ie, CV death, nonfatal myocardial infarction, or nonfatal stroke).. Overall, 11,066 of 14,671 TECOS participants (75.4%) had LDL-C measured at baseline. Median age was 65 years, 72% were male, and median T2D duration was 10 years. Overall, 82.5% of patients were on statins; only 5.8% were on ezetimibe. At baseline, 14.3% had LDL-C ≤55 mg/dL, 18.4% between 55.1 and 70 mg/dL, 35% between 70.1 and 100 mg/dL, and 32.3% >100 mg/dL. Each 10 mg/dL higher LDL-C value was associated with a higher risk of MACE (HR 1.05, 95% CI 1.03-1.07) or CV death (HR 1.06, 95% CI 1.04-1.09).. Although most high-risk patients with T2D and CV disease were on lipid-lowering therapy, only 1:3 had LDL-C <70 mg/dL and 1:6 had LDL-C <55 mg/dL. Each 10 mg/dL higher LDL-C value was associated with a 5% and 6% higher 5-year incidence of MACE and CV death, respectively. (TECOS, NCT00790205).

Topics: Aged; Atherosclerosis; Cardiovascular Diseases; Cholesterol, LDL; Diabetes Mellitus, Type 2; Double-Blind Method; Ezetimibe; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypoglycemic Agents; Male; Middle Aged; Myocardial Infarction; Reference Values; Sitagliptin Phosphate; Stroke

The effects of β-blocker therapy in patients with type 2 diabetes (T2D) and established atherosclerotic cardiovascular disease (ASCVD) are unclear. We sought to evaluate associations between β-blocker use in T2D with ASCVD and cardiovascular (CV) outcomes.. In patients with T2D and ASCVD enrolled in the Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS), an inverse probability of treatment-weighted Cox proportional hazards model was used to examine the association between baseline β-blocker therapy (at randomization) and the primary CV composite (defined as CV death, non-fatal myocardial infarction [MI], non-fatal stroke, or hospitalization for unstable angina), including in subgroups with prior MI and heart failure (HF); other outcomes evaluated included individual components of the primary composite, hospitalization for HF, and severe hypoglycemic events.. Of the 14,671 patients randomized, 9322 (64%) were on a β-blocker at baseline; these patients were more likely to have prior MI or HF. Over a median 3.0 (25th, 75th percentile: 2.2, 3.6) years, the risk of the primary CV composite was significantly higher with baseline β-blocker use versus no β-blocker use (4.5 vs. 3.4 events/100-patient years, adjusted hazard ratio [HR] 1.17, 95% confidence interval [CI] 1.05-1.29); no significant interaction was noted for patients with versus without prior MI or HF. Baseline β-blocker use was not associated with risks for severe hypoglycemic events (HR 1.14, 95% CI 0.88-1.48).. In this observational analysis of T2D and ASCVD, baseline β-blocker use was not associated with risks for severe hypoglycemia yet also was not associated with CV risk reduction over 3 years of follow-up, supporting a randomized examination of chronic β-blocker therapy in this patient population. (TECOS ClinicalTrials.gov number, NCT00790205).

Topics: Adrenergic beta-Antagonists; Aged; Angina, Unstable; Atherosclerosis; Atrial Fibrillation; Cardiovascular Diseases; Cause of Death; Diabetes Mellitus, Type 2; Double-Blind Method; Female; Heart Failure; Hospitalization; Humans; Hypoglycemia; Hypoglycemic Agents; Kaplan-Meier Estimate; Male; Middle Aged; Myocardial Infarction; Proportional Hazards Models; Sitagliptin Phosphate; Stroke; Treatment Outcome

We investigated the use of different antithrombotic therapies at baseline among patients with a history of atrial fibrillation (AF), type 2 diabetes, and established atherosclerotic cardiovascular disease (ASCVD) enrolled in the Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS).. TECOS participants with a history of AF were stratified by CHA. Of the 14,671 TECOS participants, 1167 (8%) had a history of AF, of whom 51.6% were using vitamin K antagonists (VKA); 31.2% used VKA alone, 16.9% used aspirin plus VKA, 1.8% used clopidogrel plus VKA, and 1.7% used aspirin and clopidogrel plus VKA. Aspirin was used by 56.8%: 30.9% used aspirin alone and 7.3% aspirin plus clopidogrel. Clopidogrel alone was used by 2.9%, and 7.3% were not using any antithrombotic medication. Participants with a history of AF had a higher risk of cardiovascular events, including hospitalization for heart failure and all-cause mortality, than those without AF. White, older men with prior myocardial infarction, heart failure, peripheral artery disease, or prior stroke were more likely to develop new-onset AF than others without these characteristics.. Almost half of high-risk AF patients with diabetes and established ASCVD in TECOS were not treated with anticoagulation therapy despite clear guideline recommendations for such therapy, highlighting the challenge and potential for clinical improvements in managing these patients in clinical practice.. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00790205.

Topics: Aspirin; Atrial Fibrillation; Clopidogrel; Diabetes Mellitus, Type 2; Double-Blind Method; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Hypoglycemic Agents; Male; Middle Aged; Platelet Aggregation Inhibitors; Sitagliptin Phosphate; Stroke; Time Factors; Treatment Outcome; Vitamin K

Clinical and safety event summaries are presented for older versus younger participants and for the treatment groups within the older cohort.. Of 14,351 participants with age recorded, 2,004 (14%) were ≥75 years old (mean age 78.3 years [SD 3.1]), with 68% men and type 2 diabetes duration median 12.0 years (IQR 7, 21). During 2.9 years median follow-up, older participants had higher rates of the primary outcome (6.46 vs. 3.67 events per 100 person-years; hazard ratio 1.72 [95% CI 1.52-1.94]), death (2.52 [2.20-2.89]), severe hypoglycemia (1.53 [1.15-2.03]), and fractures (1.84 [1.44-2.35]). In the older cohort, sitagliptin did not significantly impact the primary composite (1.10 [0.89-1.36]), death (1.05 [0.83-1.32]), heart failure hospitalization (0.99 [0.65-1.49]), severe hypoglycemia (1.03 [0.62-1.71]), rates of acute pancreatitis and pancreatic cancer, or serious adverse events.. Among older patients with well-controlled type 2 diabetes and cardiovascular disease, sitagliptin had neutral effects on cardiovascular risk and raised no significant safety concerns.

Topics: Aged; Aged, 80 and over; Body Mass Index; Diabetes Mellitus, Type 2; Double-Blind Method; Female; Follow-Up Studies; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Male; Middle Aged; Myocardial Infarction; Risk Factors; Sitagliptin Phosphate; Stroke; Treatment Outcome

Impaired glucose tolerance is present in one third of patients with a TIA or ischemic stroke and is associated with a two-fold risk of recurrent stroke. Metformin improves glucose tolerance, but often leads to side effects. The aim of this study is to explore the feasibility, safety, and effects on glucose metabolism of metformin and sitagliptin in patients with TIA or minor ischemic stroke and impaired glucose tolerance. We will also assess whether a slow increase in metformin dose and better support and information on this treatment will reduce the incidence of side effects in these patients.. The Metformin and sitAgliptin in patients with impAired glucose tolerance and a recent TIA or minor ischemic Stroke trial (MAAS trial) is a phase II, multicenter, randomized, controlled, open-label trial with blinded outcome assessment. Non-diabetic patients (n = 100) with a recent (<6 months) TIA, amaurosis fugax or minor ischemic stroke (modified Rankin scale ≤ 3) and impaired glucose tolerance, defined as 2-hour post-load glucose levels between 7.8 and 11.0 mmol/L after repeated standard oral glucose tolerance test, will be included. Patients with renal or liver impairment, heart failure, chronic hypoxic lung disease stage III-IV, history of lactate acidosis or diabetic ketoacidosis, pregnancy or breastfeeding, pancreatitis and use of digoxin will be excluded. The patients will be randomly assigned in a 1:1:2 ratio to metformin, sitagliptin or "no treatment." Patients allocated to metformin will start with 500 mg twice daily, which will be slowly increased during a 6-week period to a twice daily dose of 1000 mg. Patients allocated to sitagliptin will be treated with a daily fixed dose of 100 mg. The study has been registered as NTR 3196 in The Netherlands Trial Register. Primary outcomes include percentage still on treatment, percentage of (serious) adverse events, and the baseline adjusted difference in 2-hour post-load glucose levels at 6 months.. This study will give more information about the feasibility and safety of metformin and sitagliptin as well as the effect on 2-hour post-load glucose levels at 6 months in patients with TIA or ischemic stroke and impaired glucose tolerance.. NTR3196 , Date of registration: 15 December 2011.

Topics: Biomarkers; Blood Glucose; Clinical Protocols; Feasibility Studies; Glucose Intolerance; Glucose Tolerance Test; Humans; Hypoglycemic Agents; Ischemic Attack, Transient; Metformin; Netherlands; Predictive Value of Tests; Research Design; Sitagliptin Phosphate; Stroke; Time Factors; Treatment Outcome

Sitagliptin, an oral dipeptidyl peptidase-4 inhibitor, lowers blood glucose when administered as monotherapy or in combination with other antihyperglycemic agents. TECOS will evaluate the effects of adding sitagliptin to usual diabetes care on cardiovascular outcomes and clinical safety. TECOS is a pragmatic, academically run, multinational, randomized, double-blind, placebo-controlled, event-driven trial recruiting approximately 14,000 patients in 38 countries who have type 2 diabetes (T2DM), are at least 50 years old, have cardiovascular disease, and have an hemoglobin A1c value between 6.5% and 8.0%. Eligible participants will be receiving stable mono- or dual therapy with metformin, sulfonylurea, or pioglitazone, or insulin alone or in combination with metformin. Randomization is 1:1 to double-blind sitagliptin or matching placebo, in addition to existing therapy in a usual care setting. Follow-up occurs at 4-month intervals in year 1 and then twice yearly until 1300 confirmed primary end points have occurred. Glycemic equipoise between randomized groups is a desired aim. The primary composite cardiovascular endpoint is time to the first occurrence of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for unstable angina, with cardiovascular events adjudicated by an independent committee blinded to study therapy. TECOS is a pragmatic-design cardiovascular outcome trial assessing the cardiovascular effects of sitagliptin when added to usual T2DM management.

Topics: Aged; Aged, 80 and over; Angina, Unstable; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Double-Blind Method; Drug Therapy, Combination; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Male; Metformin; Middle Aged; Myocardial Infarction; Pioglitazone; Pyrazines; Research Design; Sitagliptin Phosphate; Stroke; Sulfonylurea Compounds; Thiazolidinediones; Treatment Outcome; Triazoles

The effect of sodium glucose cotransporter 2 inhibitors (SGLT2i) on the total (first and recurrent) burden of cardiovascular (CV) hospitalizations, including hospitalization for heart failure, myocardial infarction, and stroke, is poorly understood.. To assess the effect of empagliflozin, an SGLT2i, on total CV hospitalizations among older adults with T2D.. Using data from Medicare fee-for-service (08/2014-09/2017), we identified 1:1 propensity score-matched cohorts of patients with T2D initiating empagliflozin versus sitagliptin or empagliflozin versus glucagon-like peptide-1 receptor agonists (GLP-1RA), balancing >140 baseline covariates. We compared the risk of first and recurrent hospitalizations with any CV condition as the primary discharge diagnosis (ICD-9: 390-459; ICD-10: I00-I99), hospitalizations for heart failure (HHF), and myocardial infarctions (MI) or stroke. We estimated treatment effects based on the Ghosh-Lin semiparametric model for recurrent events as primary and joint frailty model as secondary analysis.. We included 11,429 matched-pairs of empagliflozin and sitagliptin initiators and 17,502 matched-pairs of empagliflozin and GLP1-RA initiators with an average age of 72 years. Empagliflozin was associated with a reduced risk of total CV hospitalizations (0.80 [0.69-0.93] vs sitagliptin; 0.88 [0.77-1.00] vs GLP-1RA) and total HHF (0.70 [0.51-0.98] vs sitagliptin; 0.76 [0.56-1.03] vs GLP1-RA) over a mean follow up of 6.3 months. No differences between treatments were observed for MI or stroke. Results were consistent for joint frailty models.. Empagliflozin, compared to sitagliptin or to a lesser extent GLP1-RA, was associated with a reduction in the burden of total CV hospitalizations and HHF in older patients with T2D.

Topics: Aged; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Heart Failure; Humans; Hypoglycemic Agents; Medicare; Sitagliptin Phosphate; Sodium-Glucose Transporter 2 Inhibitors; Stroke; United States

Limited data are available about the cardiovascular (CV) safety and efficacy of sitagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor, in ischemic stroke patients with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD). Ischemic stroke patients with T2DM and CKD were selected from the Taiwan National Health Insurance Research Database (NHIRD) from March 1, 2009 to December 31, 2011. A total of 1375 patients were divided into 2 age- and gender-matched groups: patients who received sitagliptin (n = 275; 20%) and those who did not (n = 1,100). Primary major adverse cardiac and cerebrovascular events (MACCE), including ischemic stroke, hemorrhagic stroke, myocardial infarction (MI), or CV death, were evaluated. During a mean 1.07-year follow-up period, 45 patients (16.4%) in the sitagliptin group and 165 patients (15.0%) in the comparison group developed MACCEs (Hazard ratio [HR] 1.05; 95% confidence interval [CI], 0.75-1.45). Compared to the non-sitagliptin group, the sitagliptin group had a similar risk of ischemic stroke (HR 0.82; 95% CI, 0.51-1.32.), hemorrhagic stroke (HR 1.50; 95% CI, 0.58-3.82), MI (HR 1.14; 95% CI, 0.49-2.65), and CV mortality (HR 1.06; 95% CI, 0.61-1.85). The use of sitagliptin in recent ischemic stroke patients with T2DM and CKD was not associated with increased or decreased risk of adverse CV events.

Topics: Aged; Cardiovascular Diseases; Cohort Studies; Databases, Factual; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Female; Humans; Hypoglycemic Agents; Male; Middle Aged; Renal Insufficiency, Chronic; Risk Factors; Sitagliptin Phosphate; Stroke; Taiwan

The cerebrovascular safety and efficacy of sitagliptin, a dipeptidyl peptidase-4 inhibitor, in patients with type 2 diabetes mellitus (T2DM) with ischemic stroke remains uncertain. The aim of this study was to assess the efficacy and safety of sitagliptin in patients with T2DM with recent ischemic stroke. We analyzed data from the Taiwan National Health Insurance Research Database between March 1, 2009, and December 31, 2011. Ischemic stroke patients were identified from individuals with T2DM. Patients who received sitagliptin were compared with those who did not to evaluate the cardiovascular safety and efficacy of sitagliptin. The primary outcome was a composite of ischemic stroke, myocardial infarction, or cardiovascular death. A total of 5145 type 2 diabetic patients with ischemic stroke met our inclusion criteria and were followed for up to 2.83 years (mean, 1.17 years). Overall, 1715 patients (33.3%) received sitagliptin and 3430 patients (66.7%) did not. The primary composite outcome occurred in 190 patients in the sitagliptin group (11.1%) and in 370 patients in the comparison group (10.8%) (hazard ratio [HR] = 1.02; 95% confidence interval [CI], 0.85-1.21). Patients treated with sitagliptin had a similar risk of ischemic stroke, hemorrhagic stroke, and all-cause mortality with an HR of 0.95 (95% CI, 0.78-1.16, P = 0.612), 1.07 (95% CI, 0.55-2.11, P = 0.834), and 1.00 (95% CI, 0.82-1.22, P = 0.989), respectively, compared with patients not treated with sitagliptin. Treatment with sitagliptin in type 2 diabetic patients with recent ischemic stroke was not associated with increased or decreased risks of adverse cerebrovascular outcomes.

Topics: Aged; Cohort Studies; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Female; Humans; Male; Middle Aged; Pyrazines; Sitagliptin Phosphate; Stroke; Treatment Outcome; Triazoles

We performed a retrospective cohort study, investigating the clinical outcomes including mortality and cardiovascular disease of sitagliptin compared with metformin monotherapies.. All patients receiving monotherapy with the dipeptidyl peptidase-IV inhibitors (DPP-IV) inhibitor sitagliptin between 1 January 2007 and 31 December 2011 were identified. All-cause mortality and a composite endpoint of stroke, acute myocardial infarction (AMI) and all-cause mortality associated with sitagliptin monotherapy were compared with metformin monotherapy. In addition, as an indicator of efficacy we analysed the hazard ratio of changing treatment.. A total of 84 756 patients were included in the analysis, 1228 (1.4%) received sitagliptin monotherapy whereas the remaining 83 528 (98.6%) patients received metformin monotherapy. Patients using metformin were younger than patients using sitagliptin (59.0 ± 15.2 vs. 62.5 ± 13.1) were less often male (51.6 vs. 54.2%) and had longer treatment duration with monotherapy (1.8 ± 1.3 vs. 0.9 ± 1.1 years). Compared with patients receiving metformin, patients using sitagliptin showed no statistically significant excess risks of all-cause mortality [hazard ratio, 1.25; 95% confidence interval (CI), 0.92-1.71; p = 0.153] or the composite endpoint (hazard ratio, 1.22; 95% CI, 0.92-1.61; p = 0.164). However, the use of sitagliptin monotherapy was associated with an increased likelihood of changing treatment (hazard ratio, 4.88; 95% CI, 4.46-5.35; p < 0.001).. In a retrospective analysis, sitagliptin monotherapy compared with metformin monotherapy was not associated with any statistical significant increased risk of all-cause mortality or the composite endpoint, but was associated with an increased likelihood of changing glucose-lowering treatment.

Topics: Denmark; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Dipeptidyl-Peptidase IV Inhibitors; Female; Humans; Hypoglycemic Agents; Male; Metformin; Middle Aged; Myocardial Infarction; Proportional Hazards Models; Pyrazines; Retrospective Studies; Sitagliptin Phosphate; Stroke; Treatment Outcome; Triazoles