pf-04971729 and Myocardial-Infarction

The global prevalence of type 2 diabetes mellitus (T2DM) is growing yearly. The efficacy of ertugliflozin (ERT), a recently licensed anti-diabetic drug, has been widely reported. However, additional evidence-based data is required to ensure its safety. In particular, convincing evidence on the effects of ERT on renal function and cardiovascular outcomes is needed.. We searched PubMed, Cochrane Library, Embase, and Web of Science for randomized placebo-controlled trials of ERT for T2DM published up to August 11, 2022. Cardiovascular events here mainly refer to acute myocardial infarction and angina pectoris (AP) (including stable AP and unstable AP). The estimated glomerular filtration rate (eGFR) was used to measure renal function. The pooled results are risk ratios (RRs) and 95% confidence intervals (CIs). Two participants worked independently to extract data.. We searched 1516 documents and filtered the titles, abstracts, and full text, 45 papers were left. Seven trials met the inclusion criteria and were ultimately included in the meta-analysis. The meta-analysis found that ERT reduced eGFR by 0.60 mL·min-1·1.733 m-2 (95% CI: -1.02--0.17, P = .006) in patients with T2DM when used for no more than 52 weeks and these differences were statistically significant. Compared with placebo, ERT did not increase the risk of acute myocardial infarction (RR 1.00, 95% CI: 0.83-1.20, P = .333) and AP (RR 0.85, 95% CI: 0.69-1.05, P = .497). However, the fact that these differences were not statistically significant.. This meta-analysis shows that ERT reduces eGFR over time in people with T2DM but is safe in the incidence of specific cardiovascular events.

Topics: Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Kidney; Myocardial Infarction

VERTIS CV was a randomised, double-blind, placebo-controlled, parallel-group, multicentre cardiovascular outcomes trial that evaluated the cardiovascular efficacy and safety of ertugliflozin in adults with type 2 diabetes and atherosclerotic cardiovascular disease. The primary objective of VERTIS CV was to show non-inferiority of ertugliflozin to placebo with respect to the primary outcome, major adverse cardiovascular events (a composite of death from cardiovascular causes, non-fatal myocardial infarction, or non-fatal stroke). The analyses reported here aimed to assess cardiorenal outcomes, kidney function, and other safety outcomes with ertugliflozin in older adults with type 2 diabetes and atherosclerotic cardiovascular disease compared with younger participants.. VERTIS CV was done at 567 centres in 34 countries. Participants (aged ≥40 years) with type 2 diabetes and atherosclerotic cardiovascular disease were randomly assigned (1:1:1) to once-daily ertugliflozin 5 mg, ertugliflozin 15 mg, or placebo in addition to background standard-of-care treatment. Random assignment was done with the use of an interactive voice-response system. The study outcomes were major adverse cardiovascular events, hospitalisation for heart failure or cardiovascular death, cardiovascular death, hospitalisation for heart failure, prespecified kidney composite outcomes, kidney function, and other assessments of safety. Cardiorenal outcomes, kidney function, and safety outcomes were evaluated by baseline age (≥65 years and <65 years [prespecified] and ≥75 years and <75 years [post hoc]). The study is registered with ClinicalTrials.gov, NCT01986881.. Between Dec 13, 2013, and July 31, 2015, and between June 1, 2016, and April 14, 2017, 8246 adults with type 2 diabetes and atherosclerotic cardiovascular disease were recruited to the study and randomly assigned. 2752 patients were assigned to ertugliflozin 5 mg, 2747 patients to ertugliflozin 15 mg, and 2747 patients to placebo. 8238 participants received at least one dose of ertugliflozin 5 mg, ertugliflozin 15 mg, or placebo. 4145 (50·3%) of 8238 participants were aged 65 years and older, including 903 (11·0%) participants aged 75 years and older. 5764 (70·0%) of 8238 participants were male and 2474 (30·0%) were female, and 7233 (87·8%) of 8238 participants were White, 497 (6·0%) were Asian, 235 (2·9%) were Black, and 273 (3·3%) were classified as other. The mean estimated glomerular filtration rate (eGFR) was lower and the type 2 diabetes duration longer for those aged 65 years and older versus those younger than 65 years, and for those aged 75 years and older versus those younger than 75 years. Cardiovascular outcomes were more common in the older age subgroups than in the younger age subgroups. Similar to the overall VERTIS CV cohort, ertugliflozin did not increase the risk of major adverse cardiovascular events, cardiovascular death or hospitalisation for heart failure, cardiovascular death alone, or the kidney composite outcome (using doubling of serum creatinine, dialysis or transplantation, or kidney death), and reduced the risk of hospitalisation for heart failure and the exploratory kidney composite outcome (using a 40% sustained eGFR decrease, dialysis or transplantation, or kidney death) in the older age subgroups (p. The effects of ertugliflozin on cardiorenal outcomes, kidney function, and safety outcomes were generally similar across age subgroups. These results have the potential to help clinical decision making by providing a longer-term evaluation of the cardiorenal safety and overall tolerability of ertugliflozin in a large population of older adults.. Merck Sharp & Dohme LLC, a subsidiary of Merck & Co, Inc, Rahway, NJ, USA in collaboration with Pfizer Inc, New York, NY, USA.

Topics: Aged; Aged, 80 and over; Arteriolosclerosis; Diabetes Mellitus, Type 2; Double-Blind Method; Female; Humans; Kidney; Myocardial Infarction; Renal Dialysis; Sodium-Glucose Transporter 2; Standard of Care; Treatment Outcome