Type 2 diabetes mellitus (T2DM) represents the main cause of chronic kidney disease (CKD) and end-stage renal disease (ESKD), and diabetic kidney disease (DKD) is a major cause of morbidity and mortality in diabetes. Despite advances in the nephroprotective treatment of T2DM, DKD remains the most common complication, driving the need for renal replacement therapies (RRT) worldwide, and its incidence is increasing. Until recently, prevention of DKD progression was based around strict blood pressure (BP) control, using renin–angiotensin system blockers that simultaneously reduce BP and proteinuria, adequate glycemic control and control of cardiovascular risk factors. Glucagon-like peptide-1 receptor agonists (GLP-1RA) are a new class of anti-hyperglycemic drugs shown to improve cardiovascular and renal events in DKD. In this regard, GLP-1RA offer the potential for adequate glycemic control in multiple stages of DKD without an increased risk of hypoglycemia, preventing the onset of macroalbuminuria and slowing the decline of glomerular filtration rate (GFR) in diabetic patients, also bringing additional benefit in weight reduction, cardiovascular and other kidney outcomes. Results from ongoing trials are pending to assess the impact of GLP-1RA treatments on primary kidney endpoints in DKD.

Weight-loss medications (WLMs) may offset the physiological adaptations in appetite and energy expenditure that promote weight regain in patients with obesity after initial weight loss (WL) with lifestyle modification (LSM). 1,2 In essentially all randomised clinical trials (RCTs) of WLMs, the addition of these drugs consistently results in a greater weight reduction than LSM alone. According to clinical guidelines, WLMs should be considered in patients with a BMI ≥30 kg/m 2 or ≥27 kg/m 2 with a weight-related comorbidity when a WL of at least 5% has not been reached after 3-6 months of an LSM programme. 3-5 Until a few years ago, the lipase inhibitor orlistat was the only WLM available in Europe for long-term clinical use.The European Medicines Agency (EMA) approved in 2015 two new drugs: liraglutide 3.0 mg, a glucagon-like peptide-1 (GLP-1) receptor agonist and the combination of the antidepressant bupropion, a dopamine and norepinephrine reuptake inhibitor, with the opioid antagonist naltrexone. In the USA, two other drugs were approved by Summary Aims: To evaluate in a real-world setting the effectiveness of two drugs, orlistat and liraglutide, in patients with overweight or obesity and insufficient weight loss (WL) after a lifestyle modification programme. Methods:Retrospective, observational cohort study comparing clinical outcomes of orlistat 120 mg three times a day and liraglutide (up to 3 mg daily) in adult patients with BMI ≥30 kg/m 2 or ≥27 kg/m 2 with at least a weight-related comorbidity who had failed to lose at least 5% of their weight after 6 months of lifestyle modification.The co-primary end-points, assessed at 3-6 months and at the end of the follow-up, were weight change from baseline, proportion of patients who lost at least 5% of their baseline weight and adjusted differences in WL between both drugs.Results: Five hundred patients, 400 in the group of orlistat (age 47.0, weight 107.8 kg) and 100 in the group of liraglutide (age 51.9 years, weight 105.1 kg), were included.Treatment with both drugs significantly reduced weight, fasting plasma glucose, systolic BP, low-density lipoprotein-cholesterol and alanine transaminase over a median follow-up period of 7 months. WL with liraglutide (−7.7 kg) was significantly greater than that observed with orlistat (−3.3 kg), and more individuals lost at least 5% of their baseline weight with liraglutide (64.7%) than with orlistat (27.4%). Rates of prediabetes significantly decreased with liraglutide in comparison to orlistat. Conclusions:In this real-world study, liraglutide showed a greater effectiveness in WL compared with orlistat and improved several obesity-associated metabolic and cardiovascular risk factors.

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In a real-world setting, ExQW significantly decreased A1C, weight, blood pressure and lipids at 6 months. Our study identified higher baseline A1C as the sole independent predictor of glycaemic response to ExQW and higher BMI and previous DDP4i treatment as predictive factors of meaningful weight response.

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The aims of this multicentric retrospective study were to assess in a real-world setting the effectiveness and safety of canagliflozin 100 mg/d (CANA100) as an add-on to the background antihyperglycemic therapy, and to evaluate the intensification of prior sodium–glucose co-transporter type 2 inhibitor (SGLT-2i) therapy by switching to canagliflozin 300 mg/d (CANA300) in patients with T2DM. One cohort of SGLT2i-naïve patients with T2DM who were initiated on CANA100 and a second cohort of patients with prior background SGLT-2i therapy who switched to CANA300 were included in the study. The primary outcome of the study was the mean change in HbA1c over the follow-up time. In total, 583 patients were included—279 in the cohort of CANA100 (HbA1c 8.05%, weight 94.9 kg) and 304 in the cohort of CANA300 (HbA1c 7.51%, weight 92.0 kg). Median follow-up periods in both cohorts were 9.1 and 15.4 months respectively. CANA100 was associated to significant reductions in HbA1c (−0.90%) and weight (−4.1 kg) at the end of the follow-up. In those patients with baseline HbA1c > 8% (mean 9.25%), CANA100 lowered HbA1c levels by 1.51%. In the second cohort, patients switching to CANA300 experienced a significant decrease in HbA1c (−0.35%) and weight (−2.1 kg). In those patients with baseline HbA1c > 8% (mean 8.94%), CANA300 lowered HbA1c levels by 1.12%. There were significant improvements in blood pressure in both cohorts. No unexpected adverse events were reported. In summary, CANA100 (as an add-on therapy) and CANA300 (switching from prior SGLT-2i therapy) significantly improved several cardiometabolic parameters in patients with T2DM.