Differential glycaemic control with basal insulin glargine 300 U/mL versus degludec 100 U/mL according to kidney function in type 2 diabetes: A subanalysis from the BRIGHT trial

Abstract

Aims Chronic kidney disease (CKD) challenges diabetes management and is associated with increased cardiovascular morbidity and mortality. We examined whether clinical outcomes with insulin glargine 300 U/mL (Gla‐300) and insulin degludec 100 U/mL (IDeg‐100) are affected by renal function in a prespecified subgroup analysis from the BRIGHT trial. Materials and methods BRIGHT (NCT02738151) was a multicentre, open‐label, randomized, active‐controlled, two‐arm, parallel‐group, 24‐week study in insulin‐naïve uncontrolled type 2 diabetes (T2D). Participants were randomized 1:1 to evening Gla‐300 (n = 466) or IDeg‐100 (n = 463) and stratified based on baseline estimated glomerular filtration rate (eGFR) for this analysis. Results Heterogeneity of treatment effect across renal function subgroups was observed ( P = .02), reflecting a greater mean glycated haemoglobin (HbA1c) reduction from baseline to week 24 with Gla‐300 versus IDeg‐100 in the eGFR <60 mL/min/1.73 m 2 subgroup (least squares mean difference: −0.43% [95% confidence interval: −0.74% to −0.12%]), while there were no differences in hypoglycaemia incidence or rates over 24 weeks in that subgroup. HbA1c reductions were similar between treatments in the other eGFR subgroups. However, heterogeneity was observed for annualized rates of anytime (24 hours) or nocturnal (00:00‐05:59 hours) confirmed hypoglycaemia (≤70 mg/dL [≤3.9 mmol/L]) over 24 weeks showing less hypoglycaemia with Gla‐300 versus IDeg‐100 in the ≥90 mL/min/1.73 m 2 . Conclusions Kidney function seems to affect the glucose‐lowering effects of Gla‐300 versus IDeg‐100 in insulin‐naïve T2D. Greater HbA1c reductions with Gla‐300 without increase in hypoglycaemia risk, were observed in patients with eGFR <60 mL/min/1.73 m 2 .

Glycaemic Control with Insulin Glargine 300 U/mL in Individuals with Type 2 Diabetes and Chronic Kidney Disease: A REALI European Pooled Data Analysis

“…Our findings are in line with post hoc analyses of the EDITION 1, 2 and 3 trials [9] and of the BRIGHT study [8]. In the post hoc patientlevel meta-analysis [9] of the EDITION trials conducted among 1247 patients with T2DM treated with once-daily evening injections of Gla-300 and who were classified into two baseline eGFR subgroups (208 patients with an eGFR \ 60 mL/min/1.73 m 2 and 1039 with an eGFR C 60 mL/min/1.73 m 2 ), the LS mean decrease in HbA1c after 6 months (-0.98% and -1.03% for those with an eGFR \ 60 and C 60 mL/min/1.73 m 2 , respectively) and the proportion of patients achieving HbA1c target \ 7.5% (54.9% and 54.0% for those with an eGFR \ 60 and C 60 mL/min/1.73 m 2 , respectively) were similar in both renal function subgroups [9].…”

“…With the exception of nocturnal severe hypoglycaemia which was rarely reported in REALI CKD (with an incidence ranging from 0% to 0.5% across the four eGFR subgroups), the incidences and event rates of hypoglycaemic events were higher in the eGFR 15-44 mL/min/ 1.73 m 2 subgroup compared with the other eGFR subgroups, which is not surprising and in line with the existing literature [8,9,19]. The observed differences between the eGFR 15-44 mL/min/1.73 m 2 subgroup and the other eGFR subgroups in the event rate and incidence of hypoglycaemia are unlikely to be related to CI confidence interval, eGFR estimated glomerular filtration rate, Gla-300 insulin glargine 300 U/mL, HbA1c haemoglobin A1c, LS least-squares, SD standard deviation, SE standard error *For the difference between the subgroups, the reference is the C 90 mL/min/1.73 m 2 subgroup…”

“…The management of T2DM in patients with CKD is especially difficult, in part because of treatment complexity and due to insufficient convincing data supporting the benefits of tight glycaemic control in this subset of patients [ 7 ]. In patients with T2DM and advanced CKD, basal insulin is considered the therapeutic option of choice, as oral glucose-lowering agents such as metformin, sulfonylureas, and sodium glucose co-transporter 2 inhibitors are less used because their glycaemic efficacy is reduced and/or the risk of hypoglycaemia or other adverse reactions is increased as a consequence of drug accumulation [ 4 , 5 , 7 , 8 ]. Insulin requirements are generally lower in patients with T2DM and renal impairment due to a decreased insulin clearance; yet, there are no guidelines regarding insulin dose adjustment in this specific population [ 5 , 9 ].…”

The Safety and Efficacy of Second-Generation Basal Insulin Analogues in Adults with Type 2 Diabetes at Risk of Hypoglycemia and Use in Other Special Populations: A Narrative Review

“…There are no RCTs that have specifically assessed the use of second-generation BI in people with T2DM and renal insufficiency. However, the use of these agents in this at-risk population can be gleaned from a meta-analysis of Gla-300 RCTs [69], some exploratory data from a subgroup analysis of BRIGHT [70] and predictive modeling data based on RWE from the LIGHTNING study [43].…”

“…There were no differences in hypoglycemia incidence or rates over 24 weeks in the \ 60 mL/min1.73 m 2 subgroup. Further investigation is required to determine if Gla-300 may allow more effective glycemia management in this vulnerable population [70].…”