Initial studies testing finerenone as a treatment for type 2 diabetes so far have been positive.

The nonsteroidal, selective mineralocorticoid receptor antagonist has shown the ability to half the progression of chronic kidney disease (CKD), while reducing the risk of cardiovascular events in this patient population.

However, despite the initial success, there is still a lot to learn whether or not this family of medicine can move to the front of the line for diabetic patients with CKD.

, George Bakris, MD, Department of Medicine, University of Chicago, called finerenone “new to the party” and said it is expected to be examined closer in the coming years.

Bakris said while the medication family has shown promise, it is unlikely they take the place of SGLT2 inhibitors, which have become increasingly popular for patients with type 2 diabetes and CKD to reduce the risk of negative cardiovascular outcomes.

The data was part of the ongoing Finerenone in Reducing Cardiovascular Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial, which will assess the drug’s cardiorenal efficacy and safety in populations with type 2 diabetes and less advanced chronic kidney disease.

Videos

More studies are planned testing the impact of finerenone.

George Bakris: The Future of Finerenone as a Diabetes Treatment

 events, increasing the importance of drugs that can help with all 3 areas of disease.

Recently, researchers presented data showing finerenone reduced the risk of CKD progression, while also lowering the prevalence of cardiovascular events in patients with type 2 diabetes.

In the past, short-term trials produced an association between administration of the nonsteroidal, selective mineralocorticoid receptor antagonist and reduction in albuminuria.

In the latest data, a team led by George Bakris, MD, Department of Medicine, University of Chicago, conducted a double-blind trial examining the effects of the treatment for a median follow-up of 2.6 years.

, Bakris explained the results of the study and why finerenone could be added to the list of beneficial treatments for type 2 diabetes patients

Although Bakris said it’s unlikely that finerenone will surpass the use of SGLT2 inhibitors for this patient population, the early results do warrant continued studies.

Finerenone could be another option to SGLT2 inhibitors for this patient population.

George Bakris, MD: Finerenone Showing Promise Treating Type 2 Diabetes

This article was originally published on 

 were more likely to experience the neurological complications, including bleeding in the brain and stroke, that come with the virus.

Based on CT and MRI images, investigators from the Perelman School of Medicine at the University of Pennsylvania determined that these chronic conditions could play a role in which patients are impacted by more than just the hallmark lung inflammation that comes with viral infection.

“COVID-19’s effects extend far beyond the chest,” said lead study author Colbey W. Freeman, M.D., chief resident in the Penn Medicine radiology department. “While complications in the brain are rare, they are an increasingly reported and potentially devastating consequence of COVID-19 infection.”

Freeman’s team will present their findings during this year’s Radiological Society of North America (RSNA) annual meeting. 

In an effort to better understand how COVID-19 impacts the body, they examined head CT and/or MRI images for patients positive for the virus who presented to the University of Pennsylvania health system from January 2020-April 2020.

A total of 81 of the 1,357 COVID-19-positive patients who were admitted underwent a brain scan prompted by either altered mental state or focal neurological deficits, including speech and vision problems.

Based on the team’s analysis, 18 patients – slightly over 20% – had findings that were considered critical, such as strokes, brain bleeds, or blocked blood vessels. And, of that group, at least half also had a pre-existing history of high blood pressure or type 2 diabetes.

“COVID-19 is associated with neurological manifestations, and hypertension and type 2 diabetes mellitus are common in individuals who develop these manifestations,” Freeman said. “These populations may be at higher risk for neurologic complications and should be monitored closely.”

The team also found that two-thirds of the patients who had critical findings were African American, indicating COVID-19 positive patients in that minority group should be monitored more closely. And, among the entire group of 18 with emergent findings, three died while in the hospital, the team said.

Although this study revealed a role for high blood pressure and type 2 diabetes in the neurological impact of the virus, investigators still do not know exactly what causes those complications.

The mechanisms could be multi-factorial, and the generally accepted belief is that infection-associated inflammation is responsible, they said. In this study, in particular, they reported blood markers for inflammation were high in patients who had critical results.

“When your body is in an inflammatory state, it produces all these molecules called cytokines to help recruit the immune system to perform its function,” Freeman said. “Unfortunately, if cytokines are over-produced, the immune response actually starts doing damage.”

Using data from this study, the team is also looking at the how frequently COVID-19-positive patients on extracorporeal membrane oxygenation (ECMO) – a pump system that circulates and replenishes oxygen in the blood – experience neurological complications. Many patients included in this study required ECMO during hospitalization.

Future plans include a larger prospective study to investigate delayed, long-term, and chronic neurologic manifestations that have not currently been identified, but that might manifest later.

Diabetes, Hypertension May Increase Risk of COVID-19 Brain Complications

Articles

About 20% of 81 positive patients experienced critical neurological complications; further, half had a pre-existing history of high blood pressure or type 2 diabetes.

Diabetes, Hypertension Linked to COVID-19-Related Neurological Complications

Using a procalcitonin-guided strategy to prescribe antibiotics in 

 patients with acute chest syndrome (ACS) was associated with reduced antibiotic exposure and no apparent adverse outcomes, according to a new study.

Procalcitonin concentration level has been linked to bacterial infection and severity. Previous guidance using these levels is reported to be safe in reducing the duration of antibiotic treatment in critically ill patients and those with community-acquired pneumonia.

Thus, in order to confirm the effectiveness of this guidance for ACS, a team led by Keyvan Razazi, MD, of Henri Mondor Univeristy Hospital, France, conducted a single-center prospective before-after study of adult patients with sickle cell disease in the medical ward and ICU.

“Antibiotic stewardship is important in this population, with locally high prevalence of penicillin-resistant pneumococcal infections and profound underdosing of antibiotics secondary to augmented renal clearance,” they wrote.

They excluded patients with severe immunosuppression, pregnancy or lactation, <18 years of age, documented extrapulmonary infection, as well as those whose who had been administered antibiotics 24 hours prior to inclusion.

The primary endpoint of the study was number of days alive without antibiotics at Day 21. Secondary endpoints sought by the investigators included compliance to procalcitonin algorithm during intervention phase, relapse, and superinfection.

Once patients began receiving antibiotics, procalcitonin concentration was assessed during the first 3 days of their ACS episode. The investigators noted that the lower limit of detection of the assay was 0.02 ng/mL, and the functional assay sensitivity was 0.06 ng/mL.

During the first phase of the study, or the control period, clinicians were not informed of procalcitonin-concentration results. Following this phase, in the intervention period, concentration measurements were then used to build an algorithm for clinicians to use as a guide for antibiotic treatment.

However, discretion still remained with the clinician to manage antibiotic use.

Overall, among the 114 screened patients, only 14 had met exclusion criteria. The rest, who were included in the study, represented a total of 103 ACS episodes (43 in the control phase, and 60 in the intervention phase).

Measurements showed that procalcitonin concentration was <0.5μg/L at Days 1–3 for 66 of 103 patients, and the higher concentration values were associated with greater severity.

Results showed that during the intervention phase, 25 of 60 (42%) patients had an interruption of antibiotic therapy within 24 hours of algorithm recommendation initiation. Further, 38% experienced a prolonged antibiotic therapy, and 20% experienced antibiotic therapy that was shorter than what was recommended in the algorithm.

Further, Razazi and colleagues noted that the number of days alive without antibiotics was higher in the intervention period (15; range, 14-18) as compared to the control phase (13; range, 13-14; 

Compared to the control phase, the proportion of patients receiving antibiotics between inclusion and Day 21 was lower in the intervention phase.

And finally, 31% of patients in the intervention phase received a ≤3 days course of antibiotics—versus 9% in the control phase.

However, the investigators did note that there were not enough proven or possible infections during the control phase to make any formal determination of the diagnostic accuracy of procalcitonin. 

“In conclusion, our preliminary results suggest that a procalcitonin-guided strategy may have a role in shortening the duration of antibiotic therapy with no apparent adverse outcomes during ACS in sickle cell disease,” they concluded. “However, the use of this biomarker to predict bacterial infection in this situation should be performed with caution.”

Procalcitonin to Reduce Antibiotic Exposure during Acute Chest Syndrome in Adult Patients with Sickle-Cell Disease

Guidance based on procalcitonin concentration levels may useful in reducing duration of antibiotic treatment for sickle cell patients with acute chest syndrome. 

Biomarker-Guided Strategy May Reduce Antibiotic Use in SCD Patients with ACS

This article was originally published on EndocrinologyNetwork.com.

Semaglutide could help reduce negative cardiovascular events for patients with type 2 diabetes, according to new research presented at the American Heart Association’s (AHA) Scientific Sessions 2020.

An analysis of data from the SUSTAIN 6 and PIONEER 6 trials indicates use of semaglutide was associated with consistent reductions in major adverse cardiovascular events regardless of baseline triglyceride levels in patients with 

The analysis, which was conducted by investigators from St. Michael’s Hospital in Toronto and Brigham and Women’s Hospital, aggregated data from the SUSTAIN 6 and PIONEER 6 trials and concluded semaglutide reduced the risk of major adverse cardiovascular events across multiple levels of baseline triglycerides.

“We found that the incidence rate for MACE in the placebo arm increased across increasing triglyceride levels as evaluated categorically in this analyses. Semaglutide generally reduced the risk of MACE and its components versus placebo across all triglyceride groups,” said Subodh Verma, MD, PhD, a cardiac surgeon-scientist at St. Michael’s Hospital, in his AHA 2020 presentation. “Results were consistent when evaluating triglycerides categorically or as a continuous variable.”

The current study was designed as a posthoc analysis of the trials to assess effects of semaglutide on MACE and its components across triglyceride levels. Briefly, SUSTAIN 6 enrolled 2735 patients and randomized to either 0.5 or 1g semaglutide once weekly or placebo therapy and PIONEER 6 enrolled 3183 and randomized them to daily oral semaglutide or placebo.

The main outcome of interest for the analysis was change in triglyceride levels over time with semaglutide versus placebo in both trials. Additionally, Investigators hoped to determine the risk of first MACE and its components by baseline triglyceride levels and time to first MACE by triglyceride levels at baseline for semaglutide and placebo when pooling data from both trials.

Upon analysis, investigators identified 6417 patients from the trials with information related to baseline triglyceride measurements, These groups were defined as triglycerides 151 mg/dL or less, 151 mg/dL to 205 mg/dL, and more than 205 mg/dL. Results indicated the mean triglycerides for each of the 3 groups were 107.3 (26.0), 176.6 (15.6), and 326.5 (197.1) mg/dL, respectively.

Investigators estimated the effect of semaglutide versus placebo on primary endpoints using Cox regression by triglyceride level categorically and continuously when adjusted for baseline triglycerides and HDL cholesterol. Investigators also noted the analysis was designed to assess impact of statin treatment in these patients as well.

After analysis, investigators determined semaglutide reduced triglycerides versus placebo by 5% in the SUSTAIN 6 trial and 6% in the PIONEER 6 trial (

Further analysis indicated the incidence of MACE with placebo increased across the increasing triglyceride groups. In comparison, semaglutide generally reduced the risk of MACE and its components across all triglyceride groups versus placebo. Additionally, results appeared to be consistent when evaluating triglycerides as a continuous variable and regardless of statin treatment among patients.

“This posthoc analysis of SUSTAIN 6 and PIONEER 6 trials pooled demonstrated that semaglutide reduced triglyceride levels versus placebo in both trials, in which over half of the patients had elevated levels at baseline,” Verma added.

Semaglutide Reduces Mace Consistently Across Baseline Triglyceride Levels in Patients With Type 2 Diabetes: A Post Hoc Analysis of the Sustain 6 and Pioneer 6 Trials

Researchers present new data from the SUSTAIN 6 and PIONEER 6 trials during the virtual AHA 2020 conference. 

Semaglutide Reduces Triglyceride Levels in Diabetic Patients

The US Food and Drug Administration (FDA) has approved lumasiran (Oxlumo) as the first drug for rare genetic disorder 

The approval, granted to Alnylam Pharmaceuticals, provides a therapeutic resolve to the condition which affects approximately 3 persons per 1 million in North American and Europe combined, and can result in kidney function and organ damage.

As the FDA additionally noted in its approval, the indication comes from collaborative work among experts and community leaders coordinated by the Oxalosis & Hyperoxaluria Foundation and the Kidney Health Initiative.

“The approval of Oxlumo represents a great triumph of community involvement to address a rare disease. It is a result of input from patients, treating physicians, experts and sponsors at a patient-focused drug development meeting and through other collaborative efforts,” said Norman Stockbridge, MD, PhD, director of the Division of Cardiology and Nephrology in the FDA’s Center for Drug Evaluation and Research, 

Primary hyperoxalurias (PHs) are driven by excess production of oxalate, a substance commonly consumed in food. As the most severe form of the condition, PH1 activity can frequently combine with calcium to cause kidney stones and deposits, leading to progressing kidney damage and even failure.

Lumasiran was evaluated in a randomized, placebo-controlled study in patients with PH1 aged 6 years and older, as well as an open-label study in patients younger than 6 years. Patients were aged 4 months to 61 years old at the first dose.

In the placebo-controlled trial, 26 patients received a monthly lumasiran injection followed by maintenance dose every 3 months, versus 13 patients who received placebo. Investigators assessed for a primary endpoint of oxalate measure via urine over 24 hours.

Treated patients reported a mean 65% reduction on oxalate, versus just 12% reduction in patients on placebo. More than half (52%) of treated patients achieved normal 24-hour urinary oxalate levels by the sixth month of assessment, versus none on placebo.

In the open-label trial, 16 patients all received lumasiran, and reported a mean 71% in urinary oxalate by the sixth month of assessment.

Common adverse events in treated patients included injection site reaction and abdominal pain.

Lumasiran originally received Orphan Drug Designation, Breakthrough Therapy Designation, and a rare pediatric disease priority review voucher from the FDA.

The indication comes from collaborative work among experts and community leaders coordinated by the Oxalosis & Hyperoxaluria Foundation and the Kidney Health Initiative.

FDA Approves First Drug for Primary Hyperoxaluria Type 1

These past few weeks have been marked by pivotal, welcomed news in the race to a 

 vaccine. So far, 3 leading pharmaceutical companies—Pfizer, Moderna, and AstraZeneca—have announced results from their respective vaccine trials.

All 3 vaccine candidates have shown promising efficacy and safety data, signals that bode well for the future of COVID-19 prevention and mitigation.

Here is a recap of where things stand so far going into this final full week of November:

Pfizer and Biontech reported 95% efficacy for their vaccine candidate beginning 28 days after the 1st dose. Last week, they submitted an Emergency Use Authorization (EUA) application to the US Food and Drug Administration (FDA).

An authorization by the FDA means that Pfizer can proceed with prioritized distribution and administration of their prepared tens of millions of doses by the new year. More than 1 billion doses will be ready by 2021.

Pfizer Submits COVID-19 Vaccine to FDA for Emergency Authorization

Moderna recently announced that their preliminary ongoing phase 3 results showed that their vaccine was 94.5% efficacious in preventing COVID-19. 

The study was designed in collaboration with the FDA and the National Institutes of Health (NIH), and included US participants with the greatest risk of COVID-19 severity.

The company is expecting to submit an EUA application for their candidate to the FDA after reviewing its available safety data.

Moderna COVID-19 Vaccine mRNA-1273 Reports 94.5% Efficacy in Early Data

Today, AstraZeneca reported that their investigational vaccine was 90% efficacious in 1 of their 2 dosing regimens.

The data showed such high efficacy was achieved with half-dose administration followed by 1 full dose a month apart. However, 2 full doses 1 month apart resulted in 62% efficacy. A combined analysis of both regimens resulted in an average efficacy of 70%.

If approved by regulatory bodies, the company’s vaccine is anticipated to reach a capacity of up to 3 billion doses for 2021 on a rolling basis.

AstraZeneca Investigational COVID-19 Vaccine Shown to be 90% Efficacious

To date, 3 vaccine candidates with favorable safety profiles show promise in offering protection against COVID-19.


The Race to a COVID-19 Vaccine: Where Things Stand

Switching from tenofovir disoproxil fumarate (TDF) to tenofovir alafenamide (TAF) could be beneficial for patients with 

In the first half of a phase 3 study, investigators demonstrated switching to tenofovir alafenamide compared to tenofovir disoproxil fumarate at week 48 for chronic hepatitis B patients who were virally suppressed on long-term TDF showed promise in achieving superior bone and renal safety.

American College of Gastroenterology (ACG) 2020 conference

, a team, led by Mandana Khalili, MD, University of California San Francisco, reported the final efficacy and safety results from the study at week 96.

In the study, 488 patients with chronic hepatitis B taking TDF were evaluated for at least 48 weeks with HBV DNA < LLOQ (local lab) for 

12 weeks and < 20 IU/mL at screening. Each patient was randomized to receive either TAF 25 mg qualifying dose (n = 243) or TDF 300 mg qualifying dose (n = 245) with a matching placebo. At week 48, each patient received open-label TAF 25 mg once daily for an additional 48 weeks.

The safety assessments in the study included changes in bone (hip and spine BMD) and renal (CrCl by Cockcroft-Gault [eGFRCG], serum creatinine) parameters. The investigators also assessed viral suppression and serological and biochemical responses in all patients.

Of the patient population, 472 individuals (997%; TAF, n = 235; TDF, n = 237) completed the 48 week double-blind treatment arm. Furthermore, 465 patients (95%; TAF, n = 233; TDF, n = 232) completed study treatment through week 96.

The investigators found virologic suppression (HBV DNA < 20 IU/mL) was similarly maintained at week 96 in patients who switched to TAF medications at baseline when compared to patients who switched to TAF after 48 weeks of TDF treatment.

In addition, the rates of ALT normalization increased in both groups at the conclusion of the study.

For the patients who switch to TAF at baseline, there were similar increases in spine BMD when compared to the patients who switched at week 48. However, increases in hip BMD were smaller. For the TDF arm of the study, eGFRCG ultimately decreased at week 48 -2.7mL/min), while an improvement was found after switching to TAF at week 96 (-0.39mL/min).

“In CHB patients on long-term TDF treatment, viral suppression was maintained, ALT normalization increased, and bone and renal safety parameters were improved at Week 96,” the authors wrote.

Currently, there are an estimated 257 million incidences of HBV infections worldwide.

The key to this is early screenings and detection, enabling doctors to start treatments as early as possible. There are several treatment options for patients, with new drugs currently being studied to further our ability to treat the virus.

A Phase 3 Study Comparing Switching: Tenofovir Disoproxil Fumarate (TDF) to Tenofovir Alafenamide (TAF) With Continued TDF Treatment in Virologically Suppressed Patients With Chronic Hepatitis B: Final Week 96 Results

The rates of ALT normalization maintained in both arms of the 96 week study.

Tenofovir Alafenamide  Helpful for Chronic Hepatitis B Patients

The US Food and Drug Administration (FDA) has expanded the indicated use of baloxavir marboxil (Xofluza) to include post-exposure 

 in patients 12 years and older after they had contacted someone with the flu.

The expanded indication, granted to Genentech, also allows for the administration of baloxavir marboxil in both granular and oral tablet form.

The second-generation flu therapy was initially approved by the FDA in October 2018 for the treatment of acute uncomplicated flu in such patients within 48 hours of symptoms presenting, and was expanded to treat persons at high risk of developing flu-related complications in the following year.

This new indication also comes at a time of heightened scrutiny around flu prevention and mitigation, as the current coronavirus 2019 (COVID-19) outbreak coinciding with the 2020-21 flu season has generated concerns of a possible winter “twindemic.”

"This expanded indication for Xofluza will provide an important option to help prevent influenza just in time for a flu season that is anticipated to be unlike any other because it will coincide with the coronavirus pandemic," Debra Birnkrant, MD, director of the Division of Antiviral Products in the FDA's Center for Drug Evaluation and Research, said in a 

. "Americans will have to be more vigilant than ever as these viruses spread concurrently."

The safety and efficacy of baloxavir marboxil in post-flu exposure prevention was observed in data from a randomized, double-blind, controlled trial involving 607 subjects aged 12 years and older exposed to a person with influenza in their home.

Participants received either baloxavir marboxil (n = 303) or placebo (n = 304). Investigators assessed for a primary endpoint of proportion of subjects who were infected with the virus and presented with fever and at least 1 respiratory symptoms between days 1-10.

Just 1% of treated participants reported such flu-like symptoms in the observed period, versus 13% of participants given placebo.

Among the most common adverse events associated with baloxavir marboxil were diarrhea, bronchitis, nausea, sinusitis, and headaches. Experts further advised that hypersensitivities, including anaphylaxis, can occur in patients taking the therapy.

Though treating patients with the flu with antiviral therapies including baloxavir marboxil within 48 hours can reduce illness duration and severity, the most recommended means to mitigate influenza burden remains the annual vaccine.

The newest indication coincides with growing concerns that COVID-19 and flu spread will cause unprecedented burden on the US this winter.

FDA Expands Baloxavir Marboxil for Preventing Household Flu Spread

Compared to control cases, there was significant elevation of metabolic parameters in patients treated for 

, and the type of drug used often mattered.

Investigators from Egypt examined patients with schizophrenia compared to healthy controls in order to evaluate the impact of antipsychotics on schizophrenic’s metabolic parameters after a period of 6 months. Between January 2010 and November 2012, the study authors involved 160 patients with schizophrenia and 50 healthy volunteers.

Among patients with schizophrenia, 59 were treated with haloperidol, 48 on clozapine, 45 on risperidone, and 38 on olanzapine. The investigators also noted the patients’ clinical evaluation, duration of illness, type of schizophrenia, detailed drug history, and BMI measures. Additionally, the patients underwent laboratory testing including fasting and post prandial blood glucose levels, total leucocytic count, liver function tests, and lipid profile at baseline and after 6 months.

The investigators determined that treatment with antipsychotics impacted fasting blood glucose levels, but was not significant in altering post prandial blood glucose measurements. They said this meant “that the factor of treatment with antipsychotic is not a contributing factor in the changes in post prandial blood glucose in such model of interaction.” They also noted that the type of drug was not significant in fasting blood glucose, but only weakly significant in post prandial blood glucose.

The lipid profile changes were not significant after 6 months, the investigators said. Changes in the lipid profile are due to other factors, and not the drugs.

Waist circumference and body weight changes were believed to stem from antipsychotic treatment, the study authors found. This was found across all medication types utilized, but patients treated with clozapine and olanzapine showed the most increase in both measures during the study period, while the risperidone-treated group showed the least changes.

For both serum glutamic oxalo-acetic transferase (SGOT) and serum glutamic-pyruvic transferase (SGPT), the study authors said that antipsychotic treatment in liver enzyme changes was significant. So was the type of drug used: the patients treated with olanzapine showed the highest changes, followed by clozapine, while patients treated with haloperidol and risperidone showed the lowest changes. 

The type of drug used was also significant in terms of the liver enzyme changes, the study authors wrote. Patients that used haloperidol showed significant rise in the total leukocyte count, while risperidone and olanzapine showed no significant rise. The investigators said patients treated with clozapine showed no significant decrease in total leukocyte count.

These findings confirm that people with mental illness and schizophrenia in particular are at risk of high morbidity and mortality compared to the general population, the study authors wrote, and lifestyle, disease, and medications are the contributing factors for this risk.

“From the results of this study we can confirm the previous conclusions that metabolic disturbance in patients of schizophrenia is realty and worsens by time,” the study authors concluded. “Antipsychotics treatment may contribute in this effect particularly the novel ones but this effect could be a perpetuating or precipitating.”

The study, “Study of Biological Parameters of Schizophrenics During 6 Months of Different Anti Psychotics Treatment,” was published online in the 

The lipid profile changes were not significant after 6 months, while the changes in the lipid profile are due to other factors and not the drugs.

All News