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ObesityWeek: GLP-1 Therapy Increases Fat Metabolism as Well As Making You Eat Less

Treatment of obesity is more complicated than simply eat less and move more – and these newer GLP-1 based therapies are increasing fat tissue metabolism as well as making you eat less.

WeightControl.com Interview with:
Prof Donal O’ Shea MB, BCh, BAO, MD, FRCPI, FRCP (UK)
UCD School of Medicine
UCD Health Sciences Centre
University College Dublin

WeightControl.com: What is the background for this study?

Response: Glucagon‐like peptide‐1 (GLP‐1) analogs are powerful weight‐loss treatments. These analogs are believed to act primarily by having a major impact on energy intake through delaying gastric emptying and promoting satiety.

We felt this was over simplistic and that it was likely that GLP-1 treatments also had an effect on the other side of the energy balance equation through increasing metabolic activity in fat tissue.

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Obesity Drugs: More Protein Needed to Offset Muscle Loss

Multiple studies now report that the amounts of skeletal muscle loss with these new powerful weight loss agents is quite large, up to 40% of weight loss.

WeightControl.com Interview with:

Steven B. Heymsfield, M.D.
Professor and Director of the Body Composition-Metabolism Laboratory
Pennington Biomedical Research Center of the
Louisiana State University System in Baton Rouge

WeightControl.com: What is the background for this study?

Response: The recent introduction of glucagon receptor-1 agonists for weight control opens a new era in obesity pharmacotherapy. The greater weight loss with the new drugs is revealing a long-standing recognition that negative energy balance is accompanied by not only decrements in body fat, but also lean protein-containing tissues such as liver, kidney, and skeletal muscle.

Sex Differences in Fat Metabolism after Fasting

WeightControl.com Interview with:
Stéphanie Abo, PhD
Applied Mathematics
University of Waterloo

WeightControl.com: What is the background for this study?

Response: Our study examines how men and women process food differently, particularly how each sex responds to a high-carb versus a high-fat diet. Obesity and related conditions, like type 2 diabetes, are major global issues, and nutrition plays a key role in managing these conditions.

Men and women metabolize fats and carbohydrates differently, especially during fasting and exercise. Using a mathematical model and computer simulations, we investigated sex differences in the processing of glucose and fat and identified candidate pathways behind these sex-specific differences. This research can help improve personalized nutrition and diet strategies for both men and women.

Cleveland Clinic Study Identifies Factors Associated with Weight Loss Success on Semaglutide or Liraglutide

Researchers found that four in 10 patients (40.7%) were persistent with their medication one year after their initial prescription’s fill. The proportion of patients who were persistent with semaglutide was 45.8% versus 35.6% in patients receiving liraglutide.

WeightControl.com Interview with:
Hamlet Gasoyan, Ph.D.
Lead author of the study and Researcher
Center for Value-Based Care Research
Cleveland Clinic

WeightControl.com: What is the background for this study?

Response: Recently, injectable forms of GLP-1 RA medications such as semaglutide have been more commonly prescribed, in part related to their ability to demonstrate clinically significant weight reduction. However, outside of randomized trial settings, data on weight loss with semaglutide or liraglutide for obesity is generally limited to 6 months of follow-up, based on brand names approved by the FDA for type 2 diabetes only, or cohorts that exclude patients who did not persist with the medication.

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Monell Scientists Locate Region of Brain Activated by GLP1 drugs That Can Reduce Food Intake Without Nausea

Because we found that GLP1 drugs can activate a neuron population in the brain to reduce food intake without nausea, the implication is that future obesity drugs could be developed to selectively promote satiety without the negative side effects.

WeightControl.com Interview with:

Amber L. Alhadeff, Ph.D.
Principal Investigator
Monell Chemical Senses Center &
Department of Neuroscience, University of Pennsylvania
Philadelphia, PA 19104

WeightControl.com: What is the background for this study?

Response: GLP1-based weight loss drugs have become extremely popular, but we don’t have a good understanding of how they work. Further, many people who take these drugs experience nausea and other gastrointestinal side effects – some more severe than others.

Because of this, we became interested in understanding whether the appetite loss and weight loss stem from the same or different neural circuits as those that mediate the nausea.

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Real World Study Compares Weight Loss with Semaglutide vs Tirzepatide

While tirzepatide (Mounjaro) was significantly more effective than semaglutide (Ozempic), patients on both medications experienced substantial weight loss and we observed no difference in the risk of GI adverse events.

WeightControl.com Interview with:
Tricia Rodriguez, PhD, MPH
Ty Gluckman, MD, MHA, FACC, FAHA, FASPC
Nick Stucky, MD, PhD
Three of the authors of the JAMA Internal Medicine study

WeightControl.com: What is the background for this study? What are the main findings?

Response: With over 70% of US adults having overweight or obesity, GLP-1s have the potential to be used by a huge number of people. We’ve seen dramatic increases in use by patients with and without type 2 diabetes in the past year, yet little real-world data exist to compare the effectiveness of two of the most common medications, semaglutide (Ozempic) and tirzepatide (Mounjaro). Head-to-head trials for patients with overweight or obesity are still months away, and even then, it remains unclear how weight loss observed in these randomized controlled trials will generalize to real-world populations. There has been evidence that these medications are effective for weight loss, but it hadn’t been clear just how effective they are, particularly in relation to each other.

While clinical trials don’t always generalize to the real-world, our findings were broadly consistent with placebo-controlled clinical trials, finding that the majority of patients on both medications experience clinically meaningful weight loss within a year on treatment. However, patients on tirzepatide (Mounjaro) were over 2 times more likely to experience 10% weight loss and 3 times more likely to experience 15% weight loss within a year, compared to patients on semaglutide (Ozempic). Our study also found that, in general, patients without type 2 diabetes experienced greater weight loss than patients with type 2 diabetes, but tirzepatide (Mounjaro) was more effective than semaglutide (Ozempic) in both groups.

The study also found a high rate of discontinuation – 55.9% of patients on tirzepatide (Mounjaro), and 52.5% of patients on semaglutide (Ozempic) within 12 months.

Gastrointestinal side effects of these medications have been widely reported as well, but we didn’t find a difference in the rates of moderate to severe gastrointestinal adverse events between the two medications.

— Tricia Rodriguez, PhD, MPH principal applied scientist, Truveta Research, and lead author on the paper

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Daily Heat Treatments May Reduce Risk of Obesity in Menopausal Women

Daily 30-minute heat treatment is safe and reduces aging-mediated tissue damage. It is a promising and effective therapeutic strategy to boost metabolism and reduce the risk of obesity and metabolic dysfunction.

WeightControl.com Interview with:
Rong Fan, MS (she/her/hers)
PhD Candidate
University of Massachusetts Amherst
Amherst, Massachusetts

WeightControl.com: What is the background for this study?

Response: As we age, our metabolism and energy expenditure decline.

Studies have shown that in women, age-related metabolic changes begin around ages 45-50 with a sharp increase, overlapping with the menopause period. This mid-life aging window is crucial and highlights the need for effective and accessible intervention strategies.

Daily whole-body heat treatment (104-113°F) for 30 minutes is a promising strategy to partially mimic the metabolic benefits and physiological response of aerobic exercise.

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Increased BMI in Teens Whose Parents were Obese in Adolescence

Knowing that offsprings of parents with obesity are at a greater risk than other children for being overweight at adolescence, the question remains what are the epigenetic factors that affect obesity.

WeightControl.com Interview with:
Gilad Twig, MD, MPH, PhD
Head of the Population Health Research Center
Sheba Medical Center, Ramat Gan, Israel.
Associate Professor, Department of Epidemiology and Preventive Medicine, School of Public Health, Faculty of Medicine
Tel-Aviv University, Tel-Aviv, Israel

WeightControl.com: What is the background for this study?

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Response: Heritability of obesity has been widely investigated, but when parental and children’s body weights are compared it is difficult to distinguish between genetic relationship and shared lifestyle. In this study we compared parents and their children’s body weights all measured at age 17.

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Two Faulty Copies of SMIM1 Gene Associated with Obesity

The vast majority of people who are struggling with their weight will not have two faulty copies of the gene and their GP should be their first port of call.

WeightControl.com Interview with:
Dr. Mattia Frontini, Sr BHF Fellow
Associate Professor Cellular Biology
Department of Clinical and Biomedical Sciences
University of Exeter Medical School
Faculty of Health and Life Sciences

Dr. Mattia Frontini, Sr BHF Fellow
Associate Professor Cellular Biology
Department of Clinical and Biomedical Sciences
University of Exeter Medical School
Faculty of Health and Life Sciences

RILD Building, Barrack Road, Exeter,

WeightControl.com: What is the background for this study? What are the main findings?

Response: The initial discovery of the gene and its faulty copy, ten years ago, was motivated by the need to develop a genetic test for a difficult to type, using traditional methods, blood group known as Vel. After this discovery was made, we discovered also that the differences in these genes that exist in the population are associated to tiny changes in the blood red cell parameters.

When the UK Biobank data became available we analysed these to determine if having the faulty copy of the gene had an effect on health. We found that people with two faulty copies of the gene (about 1 in 5000) are heavier than those who don’t. They have altered lipids in their blood and they use less energy given the same caloric intake. The excess going being stored as fat.

Ultraprocessed Plant-Based Foods May Not Be Good for Your Heart

Our findings showed eating a plant-based diet can be beneficial, except when it is based on ultra-processed foods.

WeightControl.com Interview with:

Fernanda Rauber, PhD
Researcher at the Centre for Epidemiological Research in Nutrition and Health (NUPENS)University of São Paulo (USP) and
Department of Preventive Medicine
School of Medicine at USP, Brazil
Lead author of this study

WeightControl.com: What is the background for this study?

Response: Although we already have substantial evidence of the negative impact of an ultra-processed food-based diet on health, solid public policies to discourage the consumption of these products are still lacking, especially in countries like the United Kingdom. Plant-based foods are recommended in many dietary guidelines, and this area has been explored by the food industry, which uses health claims (vegetarian, vegan, plant-based) to promote its products.

With a growing population adopting plant-based diets, studying the role of food processing in plant-based dietary patterns and its relation to cardiovascular diseases can help refine guidelines to incorporate considerations about food processing in their recommendations.

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