Bengt-Olov Tengmark

BACKGROUND: In patients with chronic kidney disease (CKD) and type 2 diabetes (T2D), finerenone, a nonsteroidal mineralocorticoid receptor antagonist, reduces cardiovascular and kidney failure outcomes. Finerenone also lowers the urine albumin-to-creatinine ratio (UACR). Whether finerenone-induced change in UACR mediates cardiovascular and kidney failure outcomes is unknown. OBJECTIVE: To quantify the proportion of kidney and cardiovascular risk reductions seen over a 4-year period mediated by a change in kidney injury, as measured by the change in log UACR between baseline and month 4. DESIGN: Post hoc mediation analysis using pooled data from 2 phase 3, double-blind trials of finerenone. (ClinicalTrials.gov: NCT02540993 and NCT02545049). SETTING: Several clinical sites in 48 countries. PATIENTS: 12 512 patients with CKD and T2D. INTERVENTION: Finerenone and placebo (1:1). MEASUREMENTS: Separate mediation analyses were done for the composite kidney (kidney failure, sustained ≥57% decrease in estimated glomerular filtration rate from baseline [approximately a doubling of serum creatinine], or kidney disease death) and cardiovascular (cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure) outcomes. RESULTS: At baseline, median UACR was 514 mg/g. A 30% or greater reduction in UACR was seen in 3338 (53.2%) patients in the finerenone group and 1684 (27.0%) patients in the placebo group. Reduction in UACR (analyzed as a continuous variable) mediated 84% and 37% of the treatment effect on the kidney and cardiovascular outcomes, respectively. When change in UACR was analyzed as a binary variable (that is, whether the guideline-recommended 30% reduction threshold was met), the proportions mediated for each outcome were 64% and 26%, respectively. LIMITATION: The current findings are not readily extendable to other drugs. CONCLUSION: In patients with CKD and T2D, early albuminuria reduction accounted for a large proportion of the treatment effect against CKD progression and a modest proportion of the effect against cardiovascular outcomes. PRIMARY FUNDING SOURCE: Bayer AG.

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.

Objective This study aimed to build on the current clinical findings and investigate physicians’ experiences and level of satisfaction in using insulin degludec/liraglutide (IDegLira) to treat patients with type 2 diabetes (T2D). Research design and methods This multicountry, European online survey included respondents from primary (n=132) and secondary (n=103) care and examined physicians’ use, confidence and satisfaction with IDegLira. To standardize responses, 24 of 28 questions pertained to an ‘average patient’ with T2D who has no major comorbidities, aged 35–70 years, with average cognitive ability/normal mental status and body mass index ≥25 kg/m 2 . Results The majority (70%) of respondents prescribe IDegLira in the same visit they first mention it, with uncontrolled glycated hemoglobin (HbA1c) (44%) and weight gain (22%) being the most common reasons. On average, physicians reported that patients weighed 95 kg and the HbA1c level was 9.0% at initiation. Physicians also reported the average HbA1c target set was 7.1%; 76% of patients achieved their target. On average, patients achieved their HbA1c target in &lt;6 months, and the average dose of IDegLira in patients in glycemic control was 28 dose steps. Respondents were more satisfied with IDegLira than basal-bolus therapy across all parameters assessed, including reaching HbA1c targets (59%), number of injections (77%) and avoiding weight gain (84%). Correspondingly, 77% of physicians reported that IDegLira had more potential to improve patient motivation compared with basal-bolus to reach target blood glucose levels. Conclusions Real-world experience of IDegLira is consistent with previous trials/studies, with no major differences between primary and secondary care. Importantly, the majority of respondents were more/much more satisfied with IDegLira than with basal-bolus therapy.

Background: There are few studies providing a more comprehensive picture of advanced hybrid closed-loop (AHCL) systems in clinical practice. The aim was to evaluate the effects of the AHCL systems, Tandem ® t: slim X2™ with Control IQ™, and MiniMed™ 780G, on glucose control, safety, treatment satisfaction, and practical barriers for individuals with type 1 diabetes. Method: One hundred forty-two randomly selected adults with type 1 diabetes at six diabetes outpatient clinics in Sweden at any time treated with either the Tandem Control IQ (TCIQ) or the MiniMed 780G system were included. Glycated hemoglobin A1c (HbA1c) and glucose metrics were evaluated. Treatment satisfaction and practical barriers were examined via questionnaires. Results: Mean age was 42 years, median follow-up was 1.7 years, 58 (40.8%) were females, 65% used the TCIQ system. Glycated hemoglobin A1c was reduced by 0.6% (6.8 mmol/mol; 95% confidence interval [CI] = 0.5-0.8% [5.3-8.2 mmol/mol]; P &lt; .001), from 7.3% to 6.7% (57-50 mmol/mol). Time in range (TIR) increased with 14.5% from 57.0% to 71.5% (95% CI = 12.2%-16.9%; P &lt; .001). Time below range (TBR) (&lt;70 mg/dL, &lt;3.9 mmol/L) decreased from 3.8% to 1.6% ( P &lt; .001). The standard deviation of glucose values was reduced from 61 to 51 mg/dL (3.4-2.9 mmol/L, P &lt; .001) and the coefficient of variation from 35% to 33% ( P &lt; .001). Treatment satisfaction increased, score 14.8 on the Diabetes Treatment Satisfaction Questionnaire (DTSQ) (change version ranging from −18 to 18, P &lt; .001). Four severe hypoglycemia events were detected and no cases of ketoacidosis. Skin problems were experienced by 32.4% of the study population. Conclusions: Advanced hybrid closed-loop systems improve glucose control with a reasonable safety profile and high treatment satisfaction. Skin problems are common adverse events.

What are the effects of liraglutide, an incretin based treatment, on glycaemic control in people with type 2 diabetes treated with multiple daily insulin injections?