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We evaluate whether the combination of sodium-glucose cotransporter-2 inhibitor(SGLT2i) and glucagon-like peptide-1 receptor agonist(GLP1RA) disproportionally increases the reporting of adverse events compared with SGLT2i or GLP1RA monotherapy in the FDA adverse event reporting system (FAERS). Adverse events related to SGLT2i and GLP1RA were screened and selected, then data from the FAERS was underwent thorough disproportionality analysis. The proportional reporting ratio(PRR) of SGLT2i-related adverse events were compared between patients using SGLT2i alone and those using both SGLT2i and GLP1RA. Similarly, the PRR of GLP1RA-related adverse events were compared between patients using GLP1RA alone and those using both SGLT2i and GLP1RA. The results showed that the PRR of SGLT2i-related adverse events including diabetic ketoacidosis(DKA), ketosis, reproductive tract adverse events, urinary tract infection, and other adverse events, decreased in individuals using both SGLT2i and GLP1RA compared with those using SGLT2i alone, and the signal of fracture was not detected. Likewise, the PRR of GLP1RA-related adverse events including gastrointestinal adverse events, gallbladder and biliary tract disease, pancreatitis, and other adverse events, decreased in individuals using both SGLT2i and GLP1RA compared with those using GLP1RA alone, the PRR of hyperlipasaemia and hyperamylasaemia increased in the combination therapy and no signal of depression, suicidal and self-injurious behaviour was detected. Adverse events reporting are not disproportionally higher among those using both SGLT-2i and GLP1RA compared with SGLT2i or GLP1RA monotherapy. • Using FAERS to evaluate the adverse event of combination of SGLT2i and GLP1RA. • The combination therapy did not increase the reporting of adverse events of SGLT2i. • The combination therapy did not increase the reporting of adverse events of GLP1RA. • The combination therapy is relatively safe. [ABSTRACT FROM AUTHOR]

Diabetes is an increasingly common co-morbidity in people living with HIV (PLWH). Given new evidence demonstrating cardiovascular benefits of sodium glucose transporter 2 inhibitors (SGLT2i) and glucagon-like peptide 1 receptor agonists (GLP1RA) in diabetic patients, we reviewed medical charts of 262 PLWH at Monash Health through a 1-year retrospective cohort study to determine the rates of their use. Prevalence of diabetes was 13.4% (35) and 60% (21) had microvascular and macrovascular complications. Only 4% (95% CI 0.1%–19.6%) of diabetic patients were receiving SGLT2i and 19% (95% CI 6%–39.4%) were receiving GLP1RA. Prescribers should carefully consider their choice of glucose-lowering medication when treating PLWH. Diabetes is increasingly common among people living with HIV (PLWH). Given new evidence demonstrating cardiovascular benefits of sodium glucose transporter 2 inhibitors (SGLT2i) and glucagon-like peptide 1 receptor agonists (GLP1 RA) in diabetic patients, we reviewed medical charts of PLWH at Monash Health to determine the rates of their use and found that only 4% of diabetic patients were receiving SGLT2i and 19% were receiving GLP1 RA. Prescribers should carefully consider their choice of glucose-lowering medication when treating PLWH. [ABSTRACT FROM AUTHOR]

Despite the significant impact of statin therapy, patients continue to face substantial residual cardiovascular risk. These risks are particularly prominent in patients with both type 2 diabetes (T2D) and atherosclerotic cardiovascular disease (ASCVD). We examine the effectiveness of a cardiometabolic clinic, embedded within a suburban cardiology private practice, in identifying and managing several of these multifaceted risks. We collated interventions for the first 100 patients with T2D and ASCVD who attended a minimum of two appointments at the clinic. Following an average of 2.4 clinic visits, 44 of 100 patients had undergone intensification of lipid-lowering therapy, with 16 initiated on PCSK9-directed therapies. This resulted in 85 of 100 patients achieving LDL-C levels below the 2022 ACC Expert Consensus Decision Pathway recommendations for intensification. Lipoprotein(a) was measured in 80 patients, revealing elevated levels in 22. At baseline, 18 and 32 patients were on glucagon-like peptide-1 receptor agonists (GLP1RA) and sodium-glucose cotransporter 2 inhibitors (SGLT2i), respectively. This increased to 80 and 66 patients on GLP1RA and SGLT2i, respectively, with 94 patients on either class and 52 patients on both. Figure 1 presents baseline and follow-up use of cardiometabolic therapies. The cardiometabolic clinic effectively identified and intensified management of several residual cardiovascular risks in patients with T2D and ASCVD. Extensive use of combination lipid-lowering therapies substantially addressed cholesterol-related risk, and initial experiences support the feasibility of high-volume implementation of GLP1RA and SGLT2i therapies in this population. [ABSTRACT FROM AUTHOR]

Growth differentiation factor 15 (GDF-15) is a stress-response cytokine proposed to be associated with body weight regulation. The primary aim was to investigate changes of circulating intact GDF-15 (wildtype, non-carrier of the rs1058587 polymorphism coding for the H2O2D mutation) and total GDF-15 (measured irrespective of the mutation) in response to liraglutide (GLP-1 receptor agonist) and lorcaserin (5-HT2C receptor agonist), two pharmacologic agents that induce food intake and weight reduction. In addition, we perform exploratory correlations of total and intact GDF-15 with clinical, hormonal and metabolo-lipidomic parameters in humans with obesity. We utilized two studies: 1) Study 1, a randomized, double-blinded, cross-over trial of liraglutide and placebo administration for 5 weeks in subjects with obesity (n = 20; BMI = 35.6 ± 5.9 kg/m2), in escalating doses starting at 0.6 mg/day on week 1 and increased every week, up to the highest dose of 3.0 mg/day during week 5. b) Study 2, a randomized, double-blinded trial of lorcaserin 10 mg twice daily, or placebo for 12-weeks in humans with obesity (n = 34 BMI = 37.4 ± 6.1 kg/m2). Total and intact GDF-15 levels were measured with novel enzyme-linked immunosorbent assays and the metabolomics and lipidomics analysis was performed with nuclear magnetic resonance spectroscopy. Total and intact GDF-15 were positively correlated with diabetes risk index and trimethylamine N-oxide and negatively with eGFR. Despite significant changes in body weight, total and intact GDF-15 were not altered in response to liraglutide or lorcaserin treatment in subjects with obesity. Total and intact GDF-15 levels are not altered in response to liraglutide or lorcaserin therapy and are thus not directly involved in the metabolic feedback loop pathways downstream of GLP1 or 5-HT2C receptor agonists. Since neither total nor intact GDF-15 levels were altered in response to weight loss, future studies are needed to elucidate the pathways activated by GDF-15 in humans and its role, if any, in body weight regulation and energy homeostasis. [Display omitted] • GDF-15 is a stress-response cytokine proposed to mediate food intake and weight regulation that has been gaining attention as a possible anti-obesity treatment. • Total and intact GDF-15 levels are not altered by weight loss or in response to liraglutide or lorcaserin treatment. • GDF-15 is not downstream of the GLP1 or 5-HT2C receptor pathways. [ABSTRACT FROM AUTHOR]