OBJECTIVE To compare efficacy and safety of dulaglutide at doses of 3.0 and 4.5 mg versus 1.5 mg in patients with type 2 diabetes inadequately controlled with metformin. RESEARCH DESIGN AND METHODS Patients were randomly assigned to once-weekly dulaglutide 1.5 mg, 3.0 mg, or 4.5 mg for 52 weeks. The primary objective was determining superiority of dulaglutide 3.0 mg and/or 4.5 mg over 1.5 mg in HbA 1c reduction at 36 weeks. Secondary superiority objectives included change in body weight. Two estimands addressed efficacy objectives: treatment regimen (regardless of treatment discontinuation or rescue medication) and efficacy (on treatment without rescue medication) in all randomly assigned patients. RESULTS Mean baseline HbA 1c and BMI in randomly assigned patients ( N = 1,842) was 8.6% (70 mmol/mol) and 34.2 kg/m 2 , respectively. At 36 weeks, dulaglutide 4.5 mg provided superior HbA 1c reductions compared with 1.5 mg (treatment-regimen estimand: −1.77 vs. −1.54% [−19.4 vs. −16.8 mmol/mol], estimated treatment difference [ETD] −0.24% (−2.6 mmol/mol), P < 0.001; efficacy estimand: −1.87 vs. −1.53% [−20.4 vs. −16.7 mmol/mol], ETD −0.34% (−3.7 mmol/mol), P < 0.001). Dulaglutide 3.0 mg was superior to 1.5 mg for reducing HbA 1c , using the efficacy estimand (ETD −0.17% [−1.9 mmol/mol]; P = 0.003) but not the treatment-regimen estimand (ETD −0.10% [−1.1 mmol/mol]; P = 0.096). Dulaglutide 4.5 mg was superior to 1.5 mg for weight loss at 36 weeks for both estimands (treatment regimen: −4.6 vs. −3.0 kg, ETD −1.6 kg, P < 0.001; efficacy: −4.7 vs. −3.1 kg, ETD −1.6 kg, P < 0.001). Common adverse events through 36 weeks included nausea (1.5 mg, 13.4%; 3 mg, 15.6%; 4.5 mg, 16.4%) and vomiting (1.5 mg, 5.6%; 3 mg, 8.3%; 4.5 mg, 9.3%). CONCLUSIONS In patients with type 2 diabetes inadequately controlled by metformin, escalation from dulaglutide 1.5 mg to 3.0 mg or 4.5 mg provided clinically relevant, dose-related reductions in HbA 1c and body weight with a similar safety profile.
<b>Objective:</b> To compare efficacy and safety of dulaglutide at doses of 3.0 and 4.5 mg versus 1.5 mg in patients with type 2 diabetes inadequately controlled with metformin. <p><b>Research Design and Methods:</b> Patients were randomized to once weekly dulaglutide 1.5 mg, 3.0 mg, or 4.5 mg for 52 weeks. Primary objective was superiority of dulaglutide 3.0 mg and/or 4.5 mg over 1.5 mg in HbA<sub>1c</sub> reduction at 36 weeks. Secondary superiority objectives included change in body weight. Two estimands addressed efficacy objectives: treatment-regimen estimand (regardless of treatment discontinuation or rescue medication) and efficacy estimand (on treatment without rescue medication) in all randomized patients.</p> <p><b>Results:</b> Mean baseline HbA<sub>1c</sub> and BMI in randomized patients (N=1842) was 8.6% (70 mmol/mol) and 34.2 kg/m<sup>2</sup>, respectively. At 36 weeks, dulaglutide 4.5 mg provided superior HbA<sub>1c</sub> reductions compared to 1.5 mg (treatment-regimen estimand: -1.77 vs ‑1.54% [-19.4 vs -16.8 mmol/mol], estimated treatment difference [ETD] -0.24% (-2.6 mmol/mol); P<0.001; efficacy estimand: -1.87 vs ‑1.53% [‑20.4 vs -16.7 mmol/mol], ETD -0.34% (-3.7 mmol/mol); P<0.001). Dulaglutide 3.0 mg was superior to 1.5 mg on HbA<sub>1c</sub> reduction using the efficacy estimand (ETD -0.17% [-1.9 mmol/mol]; P=0.003) but not the treatment-regimen estimand (ETD -0.10% [-1.1 mmol/mol ]; P=0.096). Dulaglutide 4.5 mg was superior to 1.5 mg for weight loss at 36 weeks for both estimands (treatment-regimen estimand: -4.6 vs -3.0 kg, ETD -1.6 kg; P<0.001; efficacy estimand: -4.7 vs -3.1 kg; ETD -1.6 kg; P<0.001). Common adverse events through 36 weeks included nausea (1.5 mg, 13.4%; 3 mg, 15.6%; 4.5 mg, 16.4%) and vomiting (1.5 mg, 5.6%; 3 mg, 8.3%; 4.5 mg, 9.3%). </p> <p><b>Conclusion:</b> In patients with type 2 diabetes inadequately controlled on metformin, escalation from dulaglutide 1.5 mg to 3.0 mg or 4.5 mg provided clinically relevant, dose-related reductions in HbA<sub>1c</sub> and body weight with a similar safety profile.</p>
Risk of type 1 diabetes at 3 years is high for initially multiple and single Ab+ IT and multiple Ab+ NT. Genetic predisposition, age, and male sex are significant risk factors for development of Ab+ in twins.
OBJECTIVE Finerenone significantly improved cardiorenal outcomes in patients with chronic kidney disease (CKD) and type 2 diabetes (T2D) in the Finerenone in Reducing Kidney Failure and Disease Progression in Diabetic Kidney Disease trial. We explored whether baseline HbA1c level and insulin treatment influenced outcomes. RESEARCH DESIGN AND METHODS Patients with T2D, urine albumin-to-creatinine ratio (UACR) of 30–5,000 mg/g, estimated glomerular filtration rate (eGFR) of 25 to <75 mL/min/1.73 m2, and treated with optimized renin–angiotensin system blockade were randomly assigned to receive finerenone or placebo. Efficacy outcomes included kidney (kidney failure, sustained decrease ≥40% in eGFR from baseline, or renal death) and cardiovascular (cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure) composite endpoints. Patients were analyzed by baseline insulin use and by baseline HbA1c <7.5% (58 mmol/mol) or ≥7.5%. RESULTS Of 5,674 patients, 3,637 (64.1%) received insulin at baseline. Overall, 5,663 patients were included in the analysis for HbA1c; 2,794 (49.3%) had baseline HbA1c <7.5% (58 mmol/mol). Finerenone significantly reduced risk of the kidney composite outcome independent of baseline HbA1c level and insulin use (Pinteraction = 0.41 and 0.56, respectively). Cardiovascular composite outcome incidence was reduced with finerenone irrespective of baseline HbA1c level and insulin use (Pinteraction = 0.70 and 0.33, respectively). Although baseline HbA1c level did not affect kidney event risk, cardiovascular risk increased with higher HbA1c level. UACR reduction was consistent across subgroups. Adverse events were similar between groups regardless of baseline HbA1c level and insulin use; few finerenone-treated patients discontinued treatment because of hyperkalemia. CONCLUSIONS Finerenone reduces kidney and cardiovascular outcome risk in patients with CKD and T2D, and risks appear consistent irrespective of HbA1c levels or insulin use.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.