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Add-on of basal insulin (BI) to intensify the ongoing therapy with glucagon-like peptide 1 receptor agonist (GLP-1 RA) is recommended, but it is unclear if free or fixed combination of BI and GLP-1 RA produce similar outcomes. A retrospective comparative effectiveness analysis of the add-on of glargine 300 U/mL (Gla-300) to ongoing GLP-1 RA vs. switch to fixed ratio combination of degludec and liraglutide (iDegLira) was performed. Real-world data collected in electronic medical records by 32 Italian diabetes clinics. Propensity score (PS) adjustment was applied to assess changes in glycated hemoglobin (HbA1c), fasting blood glucose (FBG), body weight, and BI dose after 6 months from Gla-300 or iDegLira initiation. Compared to iDegLira group (N = 260), Gla-300+GLP-1 RA group (N = 255) had older age and higher levels of HbA1c (9.1 vs. 8.9%). After 6 months, statistically significant greater FBG improvement [estimated mean difference and 95% confidence intervals: −24.05 mg/dl (−37.04; −11.06; p = 0.0003) and BI dose increase [+0.03 U/kg (95%CI 0.00; 0.06); p = 0.009] were found in the free vs. fixed combination group, although low doses of BI (0.2 U/kg) were reached in both groups. Trends of larger HbA1c and body weight reductions with the free combination were also found, without reaching the statistical significance. Although inertia in insulin initiation and titration was documented in both groups, higher benefit on FBG control was obtained with free vs. fixed combination, likely due to a better titration of BI and GLP-1 RA. • Addition of basal insulin (BI) to GLP-1 RA is a recommended intensification approach. • It is unclear if starting BI in free or fixed combination with GLP-1 RA produce similar results. • Larger benefit on fasting blood glucose was obtained with free vs. fixed combination. • A better titration of BI and GLP-1 RA was documented with the free combination. • Clinical inertia in titration was documented in both approaches. [ABSTRACT FROM AUTHOR]

Aims: Glomerular hyperfiltration characterises the earliest stage of diabetic nephropathy and predicts adverse kidney and cardiovascular outcomes. We aimed to assess the prevalence and risk factors of glomerular hyperfiltration in a population‐based contemporary cohort of individuals with type 2 diabetes (T2D). Materials and Methods: The prevalence of unequivocal glomerular hyperfiltration (defined by an estimated glomerular filtration rate >120 mL/min/1.73 m2) and its associated risk factors were identified in a cohort of 202,068 adult patients with T2D receiving specialist care in 2021–2022, whose center‐aggregated data were automatically extracted from electronic medical records of 75 diabetes clinics in Italy. Results: Glomerular hyperfiltration was identified in 1262 (0.6%) participants. The prevalence of glomerular hyperfiltration varied widely across centers (0%–3.4%) and correlated with mean center age, HbA1c, body mass index (BMI), and low‐density lipoprotein cholesterol. Patients in centers with high glomerular hyperfiltration prevalence (>0.8%) were more often men and had lower age and BMI, but more frequent albuminuria and worse glucose, lipid, and blood pressure control, compared with low‐normal prevalence centers. Conclusions: Unequivocal glomerular hyperfiltration can be identified in up to 3.4% of patients receiving up‐to‐date specialist diabetes care. Glomerular hyperfiltration prevalence varies across centers and substantially increases with suboptimal control of metabolic risk factors, which would require improved management to mitigate the negative health consequences of this pathological condition. [ABSTRACT FROM AUTHOR]

To assess intensification approaches with basal insulin (BI) following glucagon-like peptide-1 receptor agonist (GLP-1 RA) treatment in type 2 diabetes (T2D). Real-world data were collected in electronic medical records by 32 Italian diabetes clinics between 2011 and 2021. Primary endpoint was the proportion of insulin-naïve T2D patients treated with GLP-1 RA who initiated (add-on or switch) BI. Secondary endpoints were: treatment approaches, mean time to BI start, effectiveness and safety. Among 7,962 eligible patients, BI was prescribed to 3,164 (39.7%; 95%CI 38.7; 40.8): 67.6% switched to BI (22.1% also starting 1–3 injections of short-acting insulin), 22.7% added BI while maintaining GLP-1 RA, and 9.7% switched to a fixed-ratio combination of GLP-1 RA and BI (FRC). Median time since the first GLP-1 RA to BI/FRC prescription was 27.4 (IQ range 11.8–53.5) months. In this study 60.3% of patients did not start BI/FRC, among whom 15.2% intensified GLP-1 RA therapy with other oral agents. Effectiveness and safety were documented in all intensification approaches with BI/FRC, but HbA1c level at intensification time of ≥9.0% and suboptimal BI titration suggested clinical inertia. Use of second generation BI and add-on to GLP-1 RA schemes increased over time and effectiveness improved. Clinical inertia should be overcome using innovative insulin options. Timely combination therapy of BI and GLP-1 RA is a valuable choice. • Real world data on therapeutic approaches after GLP-1 RA treatment are missing. • Basal insulin plays a key role in intensifying previous therapy with GLP-1 RA. • RESTORE-G study found that about 40% of the patients intensified GLP1-RA with basal insulin. • Add-on (free or fixed combination) or switch schemes are adopted. • Effectiveness and safety of intensification approaches, but also clinical inertia, were documented. [ABSTRACT FROM AUTHOR]

Aims: To investigate the effects of glucose‐lowering agents on all‐cause mortality, and cardiovascular and renal outcomes in adults with type 2 diabetes. Methods: A MEDLINE and EMBASE search was performed to identify randomized controlled trials, published up to 28 February 2022, with a follow‐up ≥52 weeks, in which glucose‐lowering drugs were compared with either placebo or active comparators. We included only trials reporting formal external adjudication of events. All‐cause mortality, 3‐point MACE (major cardiovascular events), and hospitalization for heart failure (HHF) were considered as principal outcomes. Doubling of serum creatinine, worsening albuminuria, and renal death were considered as secondary endpoints. Results: We included randomized controlled trials performed on metformin (n = 17), pioglitazone (n = 20), alpha‐glucosidase inhibitors (n = 9), insulin secretagogues (n = 42), dipeptidyl‐peptidase‐4 inhibitors (n = 67), glucagon‐like peptide‐1 receptor agonists (n = 45) or sodium‐glucose co‐transporter‐2 inhibitors (SGLT‐2i; n = 42) and insulin (n = 18). Glucagon‐like peptide‐1 receptor agonist and SGLT‐2i were associated with a significant reduction in all‐cause mortality [Mantel‐Haenszel odds ratio (MH‐OR), 95% confidence interval: 0.88 (0.83; 0.95) and 0.85 (0.79; 0.91), respectively] and MACE [MH‐OR, 95% confidence interval: 0.89 (0.84; 0.94) and 0.90 (0.84; 0.96), respectively]. SGLT‐2i was associated with a reduced risk of HHF [MH‐OR 0.68 (0.62; 0.75)], worsening albuminuria [MH‐OR 0.67 (0.55; 0.80)] and doubling of serum creatinine [MH‐OR 0.58 (0.44; 0.79)]. Metformin and pioglitazone were associated with a significantly lower risk of MACE [MH‐OR 0.60 (0.47; 0.80) and 0.85 (0.74; 0.97), respectively] and pioglitazone with a higher risk of HHF [MH‐OR 1.30 (1.04; 1.62)]. Insulin secretagogues were associated with increased risk of all‐cause mortality [MH‐OR 1.12 (1.01; 1.24)] and MACE [MH‐OR 1.19 (1.02; 1.39)]. Conclusions: The results of this updated meta‐analysis need to be considered in the choice of drug treatment for type 2 diabetes mellitus, which cannot be merely based on the effect of glucose‐lowering drugs on long‐term glycaemic control. [ABSTRACT FROM AUTHOR]