More than Just for Diabetes: SGLT2 Inhibitors Benefit Patients with Heart Failure

SGLT2 inhibitors, from being merely an antidiabetic drug, are contributing a lot to the global fight against cardiovascular and renal diseases. Interview with:
Bernardo Cortese, MD FESC FSCAI
Interventional Cardiologist
President, Scientific Committee Fondazione Ricerca e Innovazione Cardiovascolare, 
CEO, DCB Academy  What is the background for this study? What are the main findings?

Response: Our report seeks to elucidate the current role of SGLT2 inhibitors in the management of cardiovascular disease and the comprehensive spectrum of heart failure, namely when the heart start deteriorating in its functions.

We start focusing on the pharmacological properties of this class of drugs, thereafter we go through a synthesis and analysis of data derived from the main clinical trials which have involved this class when applied to the cardiovascular patient. Specifically, we aim to consolidate findings that substantiate the safety profile of SGLT2 inhibitors concerning cardiac, renal, and metabolic parameters. Furthermore, our study explores the therapeutic impact of these agents in the context of managing and treating type 2 diabetes.

These “glucoscape maestros”, initially prescribed to diabetic patients, showed a great safety and benefit profile in patients with renal impairment and, most importantly, with a failing heart.

EASD: Analysis Finds More Weight Loss (and side effects) with Tirzepatide in Type 2 Diabetes

Our analysis can help healthcare professionals make informed choices for managing type 2 diabetes, especially for those patients for whom weight loss is an important goal. However, like any medication, it’s crucial to consider the entire profile of tirzepatide, including side effects. Interview with:

Dr Thomas Karagiannis MD
Aristotle University of Thessaloniki
Thessaloniki, Greece  What is the background for this study? What are the main findings?

Response: Previous individual studies have shown that both subcutaneous semaglutide and tirzepatide are very effective in managing blood sugar and reducing body weight in people with type 2 diabetes. However, direct comparisons between these medications have been limited.

In our study, we used a technique called a network meta-analysis to indirectly compare the two. This method allowed us to derive results by examining other trials that compared either of the drugs with placebo or another treatment.

Our findings indicated that tirzepatide had a stronger effect than semaglutide in controlling blood sugar and aiding weight loss. For example, those on the highest dose of tirzepatide lost, on average, 5.7 kg more than those on the highest dose of semaglutide. But, it’s worth mentioning that some side effects, especially related to the digestive system, were slightly more common with the high dose of tirzepatide.

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Heart Benefits of Wegovy (semaglutide) Extend Beyond Weight Loss

This trial found that among the participants taking Wegovy the incidence of MACE was 20% lower than those with usual care. Interview with:
Assistant Professor
Department of Surgery
Division of Bariatric and Minimally Invasive Surgery
Director of Bariatric Surgery
American Board of Obesity Medicine, Diplomate
Instagram @tulane_bariatric_center  What is the background for this study? 

Response: The SELECT trial evaluated over 17,000 patients with a history of overweight or obesity and cardiovascular disease. They randomized patients to usual care versus Wegovy (semaglutide), which is an anti-obesity medication.  It is important to note that none of the participants had diabetes. 

They evaluated the incidence of Major Adverse Cardiaovascular Events (MACE) for up to 5 years for all participants.  

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Genetic Platform Can Allow Some Meds to Be Repurposed for Obesity and Type 2 Diabetes

In the current project we developed genetically informed repurposed medications to tackle obesity and type 2 diabetes (T2D) Interview with:
Professor Murray Cairns. 
Sahar El Shair, PhD student
University of Newcastle, NSW, Australia  What is the background for this study? 

Response: The background is that we want to improve global health by making a significant impact on chronic disease. Many of these complex disorders have a substantial genetic risk but this risk involves hundreds of genes (unlike the simple genetic disorders that people are more familiar with caused by a single gene) and manifests differently in different people.

To break through this problem we developed a platform for aggregating and scoring an individual’s risk for complex disorders in gene networks that can be modulated by drugs. This includes new drugs, existing drugs and those that are currently used for other conditions.  

Model Predicts Success of Weight Control Programs

We know that many people living with obesity do not want to attend health care appointments after a perceived “failure” of a weight loss intervention Interview with:
Prof Jennifer Logue 
Associate Dean (Research) Faculty of Health and Medicine
Lancaster University
Deputy Clinical Director | NIHR CRN North West Coast
Professor of Metabolic Medicine | Lancaster University
Hon Consultant in Metabolic Medicine
Blackpool Victoria Hospital  What is the background for this study? 

Response: Currently, many providers may offer more intensive therapies to every patient as they don’t believe behavioural programmes are effective, when they are for many people. Other providers leave patients struggling in a behavioural programme and they will disengage, reinforcing self-stigma.

Time Restricted Eating Reduced Glucose Levels Study of Type 2 Diabetes

​For our study, the time window in which participants were allowed to eat was delibarately set to daytime, with the last meal being ingested at 6 PM the latest. We did this so that the time-window fits in the natural, internal day-night rhythm of humans. Interview with:
Charlotte Andriessen
Department of Nutrition and Movement Sciences
Maastricht University  What is the background for this study?  What are the main findings?

Response: In our modern 24h society, most people spread their food intake over at least 14 hours per day. As such, they lack a pronounced fasting state during the night and energy stores are hardly being depleted. Here, we wanted to re-store this pronounced overnight fast in people with type 2 diabetes, by limiting their habitual food intake to a 10-hour daily time window (time restricted eating, TRE) for a period of 3 weeks.

We hypothesized that the utilization of energy stores during the night would increase the need to re-fuel these stores with the first meal of the day, and would therefore result in a better energy uptake via the hormone insulin; i.e. would result in better insulin sensitivity. Although we did not find insulin sensitivity to be increased with TRE, we did find that fasting- and 24h glucose levels were decreased as compared to our control condition, in which participants spread their habitual food intake over at least 14 hours per day. Moreover, our volunteers spent more time in the normal glucose range, whereas the time restricted eating regime did not increase the time spent in hypoglyceamia. 

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BELVIQ® : FDA Accepts Eisai’s Supplemental New Drug Application to Update the Labeling For Anti-Obesity Agent Interview with:

Dr. Lynn Kramer, MD FAAN

Dr. Lynn Kramer

Dr. Lynn Kramer, MD FAAN
VP and Chief Clinical Officer & Chief Medical Office
Eisai Co., Ltd  What is the background for this announcement? 

Response: On February 25th, Eisai announced that the U.S. Food and Drug Administration (FDA) accepted its supplemental New Drug Application to potentially update the label for BELVIQ® (lorcaserin HCI) CIV 10 mg twice-daily/BELVIQ XR (lorcaserin HCI) CIV once daily  to include long-term efficacy and safety data from CAMELLIA-TIMI 61, a clinical trial of BELVIQ in 12,000 overweight and obese patients with cardiovascular (CV) disease and/or multiple CV risk factors such as type 2 diabetes mellitus (T2DM).

CAMELLIA-TIMI 61 is the first completed large-scale cardiovascular outcomes clinical trial for a weight loss agent. As reported and published in the New England Journal of Medicine on August 26th, the results showed that CAMELLIA-TIMI 61 met its primary safety objective, finding that long-term treatment with BELVIQ did not increase incidence of MACE in overweight and obese patients at high risk for a CV event (HR 0.99; 95% CI: 0.85 to 1.14; p<0.001). Since the study met the primary safety endpoint for non-inferiority for MACE, the study continued to assess for the primary efficacy endpoint assessing whether or not BELVIQ reduced the incidence of major CV events compared to placebo for a broader composite endpoint, MACE+ (consisting of cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, hospitalization due to unstable angina, heart failure or coronary revascularization). Although superiority to placebo was not met, BELVIQ was non-inferior to placebo on the MACE+ composite, with similar event rates for BELVIQ and placebo. 

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