Clinical Perspectives on the Use of Subcutaneous and Oral Formulations of Semaglutide

Early and effective glycemic control can prevent or delay the complications associated with type 2 diabetes (T2D). The benefits of glucagon-like peptide-1 receptor agonists (GLP-1RAs) are becoming increasingly recognized and they now feature prominently in international T2D treatment recommendations and guidelines across the disease continuum. However, despite providing effective glycemic control, weight loss, and a low risk of hypoglycemia, GLP-1RAs are currently underutilized in clinical practice. The long-acting GLP-1RA, semaglutide, is available for once-weekly injection and in a new once-daily oral formulation. Semaglutide is an advantageous choice for the treatment of T2D since it has greater efficacy in reducing glycated hemoglobin and body weight compared with other GLP-1RAs, has demonstrated benefits in reducing major adverse cardiovascular events, and has a favorable profile in special populations (e.g., patients with hepatic impairment or renal impairment). The oral formulation represents a useful option to help improve acceptance and adherence compared with injectable formulations for patients with a preference for oral therapy, and may lead to earlier and broader use of GLP-1RAs in the T2D treatment trajectory. Oral semaglutide should be taken on an empty stomach, which may influence the choice of formulation. As with most GLP-1RAs, initial dose escalation of semaglutide is required for both formulations to mitigate gastrointestinal adverse events. There are also specific dose instructions to follow with oral semaglutide to ensure sufficient gastric absorption. The evidence base surrounding the clinical use of semaglutide is being further expanded with trials investigating effects on diabetic retinopathy, cardiovascular outcomes, and on the common T2D comorbidities of obesity, chronic kidney disease, and non-alcoholic steatohepatitis. These will provide further information about whether the benefits of semaglutide extend to these other indications

The diabetic lung: An easy target for SARS-CoV-2?

No abstract available

The sentiment analysis of tweets as a new tool to measure public perception of male erectile and ejaculatory dysfunctions

Twitter is a social network based on "tweets," short messages of up to 280 characters. Social media has been investigated in health care research to ascertain positive or negative feelings associated with several conditions but never in sexual medicin

Titratable fixed-ratio combination of insulin glargine plus lixisenatide: A simplified approach to glycemic control in type 2 diabetes mellitus

Approximately 50% of patients with type 2 diabetes mellitus (T2DM) do not achieve glycemic targets and require treatment intensification. A fixed-ratio combination of a glucagon-like peptide-1 receptor agonist (GLP-1 RA) with basal insulin, such as lixisenatide with insulin glargine (iGlarLixi), exploits the complementary mechanisms of action of each component to address hyperglycemia while mitigating potential adverse events (AEs). The iGlarLixi dose is titrated considering the effect of basal insulin on fasting plasma glucose, and the fixed-ratio combination ensures that the lixisenatide dose never exceeds 20 μg/day. We describe the characteristics of iGlarLixi therapy, based on the LixiLan clinical program, and provide guidance on the characteristics of patients likely to benefit from such treatment in routine clinical practice. In the phase III LixiLan trials, iGlarLixi resulted in significantly greater reductions in glycated hemoglobin (HbA1c), better achievement of HbA1c targets, less glycemic variability versus insulin glargine, lixisenatide or GLP-1 RA alone, and was associated with weight control, less hypoglycemia versus insulin glargine, and fewer GI AEs versus lixisenatide. Findings were consistent regardless of age, diabetes duration, and baseline HbA1c. The efficacy, safety, and convenient once-daily administration schedule of iGlarLixi make it a valuable treatment option for patients with T2DM requiring treatment intensification

Editorial: Reviews and Novel Clinical Perspectives on Semaglutide: A GLP-1 Receptor Agonist With Both Injectable and Oral Formulations

No abstract availabl

Renoprotection with SGLT2 inhibitors in type 2 diabetes over a spectrum of cardiovascular and renal risk

Approximately half of all patients with type 2 diabetes (T2D) develop a certain degree of renal impairment. In many of them, chronic kidney disease (CKD) progresses over time, eventually leading to end-stage kidney disease (ESKD) requiring dialysis and conveying a substantially increased risk of cardiovascular morbidity and mortality. Even with widespread use of renin–angiotensin system blockers and tight glycemic control, a substantial residual risk of nephropathy progression remains. Recent cardiovascular outcomes trials investigating sodium–glucose cotransporter 2 (SGLT2) inhibitors have suggested that these therapies have renoprotective effects distinct from their glucose-lowering action, including the potential to reduce the rates of ESKD and acute kidney injury. Although patients in most cardiovascular outcomes trials had higher prevalence of existing cardiovascular disease compared with those normally seen in clinical practice, the proportion of patients with renal impairment was similar to that observed in a real-world context. Patient cardiovascular risk profiles did not relevantly impact the renoprotective benefits observed in these studies. Benefits were observed in patients across a spectrum of renal risk, but were evident also in those without renal damage, suggesting a role for SGLT2 inhibition in the prevention of CKD in people with T2D. In addition, recent studies such as CREDENCE and DAPA-CKD offer a greater insight into the renoprotective effects of SGLT2 inhibitors in patients with moderate-to-severe CKD. This review outlines the evidence that SGLT2 inhibitors may prevent the development of CKD and prevent and delay the worsening of CKD in people with T2D at different levels of renal risk

Cardiovascular protection with sodium-glucose co-transporter-2 inhibitors in type 2 diabetes: Does it apply to all patients?

Patients with type 2 diabetes (T2D) are at an increased risk of cardiovascular disease (CVD). Cardiovascular risk in these patients should be considered as a continuum, and comprehensive treatment strategies should aim to target multiple disease risk factors. Large-scale clinical trials of sodium-glucose co-transporter-2 (SGLT2) inhibitors have shown an impact on cardiovascular outcomes, including heart failure hospitalization and cardiovascular death, which appears to be independent of their glucose-lowering efficacy. Reductions in major cardiovascular events appear to be greatest in patients with established CVD, particularly those with prior myocardial infarction, but are independent of heart failure or renal risk. Most large-scale trials of SGLT2 inhibitors predominantly include patients with T2D with pre-existing CVD and high cardiovascular risk at baseline, limiting their applicability to patients typically observed in clinical practice. Real-world evidence from observational studies suggests that there might also be beneficial effects of SGLT2 inhibitors on heart failure hospitalization and all-cause mortality in various cohorts of lower risk patients. The most common adverse events reported in clinical and observational studies are genital infections; however, the overall risk of these events appears to be low and easily managed. Similar safety profiles have been reported for elderly and younger patients. There is still some debate regarding the safety of canagliflozin in patients at high risk of fracture and amputation. Outstanding questions include specific patterns of cardiovascular protection according to baseline risk

Efficacy and safety of GLP-1 receptor agonists as add-on to SGLT2 inhibitors in type 2 diabetes mellitus: A meta-analysis

GLP-1 receptor agonists (GLP-1RA) and SGLT2 inhibitors (SGLT2i) have been associated with improved glycemic control, body weight loss and favorable changes in cardiovascular risk factors and outcomes. We conducted a systematic review and meta-analysis to evaluate the effects of the addition of GLP-1RA to SGLT2i in patients with type 2 diabetes mellitus and inadequate glycemic control. Six databases were searched until March 2019. Randomized controlled trials (RCT) with a follow-up of at least 24 weeks reporting on HbA1c, body weight, systolic blood pressure, lipids, achievement of HbA1c < 7%, requirement of rescue therapy due to hyperglycemia and hypoglycemic events were selected. Four RCTs were included. Compared to SGLT2i, the GLP-1RA/SGLT2i combination was associated with greater reduction in HbA1c (−0.74%), body weight (−1.61 kg), and systolic blood pressure (−3.32 mmHg). A higher number of patients achieved HbA1c < 7% (RR = 2.15), with a lower requirement of rescue therapy (RR = 0.37) and similar incidence of hypoglycemia. Reductions in total and LDL cholesterol were found. The present review supports treatment intensification with GLP-1RA in uncontrolled type 2 diabetes on SGLT2i. This drug regimen could provide improved HbA1c control, together with enhanced weight loss and blood pressure and lipids control

a consensus statement for the clinical use of the renal sodium glucose co transporter 2 inhibitor dapagliflozin in patients with type 2 diabetes mellitus

ABSTRACTIntroduction: The present review developed a clinical consensus based on a Delphi method on Dapagliflozin, a selective inhibitor of the renal sodium-glucose co-transporter-2 (SGLT2-I) in the treatment of patients with Type 2 diabetes mellitus.Areas covered: Panel members, using a 5-point scale, were asked to rate 9 statements on pharmakodinamic, mode of action on glycaemic and extra-glycaemic effects, and safety of dapaglifozin, Members also aimed to identify the patient most susceptible to the treatment with dapagliflozin .Expert commentary: Dapagliflozin is effective in lowering the plasma glucose concentration with a good safety profile. Dapagliflozin can be utilized in combination with all other antihyperglycaemic agents at all stages of the disease: however, a reduced GFR limits its efficacy. As for the other drugs of the class, Dapagliflozin positively modifies other risk factors for CV disease: these effects will be tested in the so far largest cardiovascular outcome trial for the SGLT2 inh..