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23andMe Study Underscores How Genes Influence Weight Loss and Side Effects of GLP1 Drugs.

The main takeaway is that your genetics can influence how well these medications work for you and what side effects you might experience.

WeightControl.com Interview with:
Dr. Adam Auton, PhD, MSc
Lead author and Vice President of Human Genomics
23andMe Research Institute

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

Response: GLP-1 medications like semaglutide and tirzepatide have transformed the treatment of obesity, but there’s enormous variation in how people respond. In clinical trials, some people lose more than 25% of their body weight while others lose almost nothing. Before our study, some of the non-genetic factors that influence response were understood – sex, age, whether someone has type 2 diabetes – but even after accounting for those, there was still a lot of unexplained variation. We suspected genetics might play a role.

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Penn Researchers: GLP-1 Medications and the Stop-Start Problem: New Research on Therapeutic Resistance

New research suggests that cycling on and off GLP-1 medications like semaglutide may cause therapeutic resistance — leaving patients potentially more obese than those who stayed on the drug continuously.

WeightControl.com Interview with
Thomas Leung, MD, PhD
Herman Beerman Professor of Dermatology
Associate Professor, and
Founding Director of the Penn 4D Center for Human Biology
University of Pennsylvania, and Physician at the
Michael Crescenz VA at Philadelphia.

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

Response: While GLP-1 medications have transformed how we manage obesity, real-world data shows that more than half of patients stop taking them within two years, and many eventually try to restart the treatment. This study was designed to understand the metabolic consequences of this stopping-and-starting pattern.

We found that when mice cycled on and off semaglutide, they developed therapeutic resistance. The drug lost its “punch” each time it was restarted, leading to much less weight loss in later rounds compared to mice that stayed on the drug without breaks.

The physical makeup of the mice between the two groups also changed. While weight loss naturally involves losing some muscle, the rapid regain during the “off” cycles was almost entirely fat. This created a “biological yo-yo” effect where the body ended up with more fat mass and less lean muscle percentage than before, which also led to poor blood sugar control. Cycling GLP-1 RA drugs made them lose their efficacy and caused mice to be 20% fatter than mice who took the medication continuously.

Continue reading “Penn Researchers: GLP-1 Medications and the Stop-Start Problem: New Research on Therapeutic Resistance”

Cleveland Clinic Study Evaluates Weight Changes after Discontinuation of Semaglutide or Tirzepatide

Among patients who started the treatment for obesity, the average weight change from baseline to discontinuation was -7.1% with semaglutide and -12.2 with tirzepatide.

WeightControl.com Interview with:
Hamlet Gasoyan, DS, PhD, MPH
Staff, Internal Medicine
Investigator, Center for Value-Based Care Research
Assistant Professor of Medicine,
Cleveland Clinic Lerner College of Medicine of Case Western Reserve
Cleveland, OH

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

Response: Despite the popularity of semaglutide and tirzepatide for obesity, discontinuation rates of these medications at 1-year range from 47% to 65%. Limited data are available about what additional weight management efforts patients pursue in real-world settings after discontinuing semaglutide or tirzepatide, and whether long-term weight changes after discontinuation follow the patterns reported in randomized clinical trials.

Weight Control Meds May Influence Not Just How Much People Eat but What they Eat

Using supermarket purchase data, we found that individuals initiating GLP-1 RA treatment showed small but significant changes in their food purchases.

WeightControl.com Interview with:
Kathrine Kold Sørensen, postdoc, PhD, cand.scient.san.publ
Copenhagen University Hospital – Steno Diabetes Center Copenhagen
Department for Clinical and Translational Research
Denmark

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

Response: GLP-1 receptor agonists are widely used in the treatment of type 2 diabetes and obesity and are known to improve weight and metabolic outcomes. Beyond weight loss, however, the mechanisms underlying these benefits are not fully understood. Smaller studies and case reports have suggested that GLP-1 RAs may influence food preferences.

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Women Increasingly Using Weight Loss Meds Shortly After Giving Birth

This shift has happened incredibly fast, and many clinicians may not realize how common postpartum GLP-1 use has already become.

WeightControl.com Interview with:

Mette Bliddal
Lektor, ph.d
Department of Clinical Research
Associate Professor, KI, OUH, Research unit of Gynaecology and Obstetrics
University of Southern Denmark

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

Response: We began noticing that more new mothers were starting weight-loss medication shortly after giving birth. Once semaglutide was approved for weight loss, the numbers rose fast. That caught our attention, especially because so little is known about using these medications during a time of major physical and hormonal changes, natural weight loss, and breastfeeding, and because the effects on breastfed infants remain unclear. This made it important to understand how common this use has already become.

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Study Evaluates Weight Control In Overweight Patients after Tirzepatide (Zepbound) Cessation

The body weight will be somehow regained after cessation of incretin based anti-obesity medicines.

WeightControl.com Interview with:
Xiaoying Li, MD
Professor and Director
Ying Chen, MD
Associate Professor

Department of Endocrinology and Metabolism
Zhongshan Hospital, Fudan University
Shanghai 200032 China

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

Response: Overweight and obesity affect more than 50% of the population in China. In the SUROMOUNT-CN study, we have reported that the GIP/GLP-1 RA, tirzepatide led to a substantial weight loss of 14.4% and 19.9% by 10 mg and 15 mg treatment for 52 weeks, respectively, in overweight or obese Chinese adults. This observational study further evaluated weight loss maintenance following tirzepatide discontinuation.

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Study Finds Weight Regained After Obesity Meds Discontinued

These medications appear to act as ongoing tools for weight maintenance, suggesting they should be viewed as chronic therapies rather than short-term interventions.

WeightControl.com Interview with:
Eric C. Nemec PharmD MEHP BCPS
Director of Research and Assessment
Associate Professor
Master of Physician Assistant Program
Sacred Heart University
Office location: 4 Hospital Plaza, Tandet Center, Stamford, CT 06902

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

Response: When we started this project, we knew that glucagon-like peptide-1 receptor agonists (GLP-1RAs) were highly effective for weight loss; however, there was limited evidence regarding the sustainability of that weight loss after treatment cessation.

Our study systematically reviewed and meta-analyzed randomized controlled trials to determine the extent of weight regain after GLP-1RA discontinuation. The key finding was that significant weight is regained after stopping therapy, and this regain was proportional to the amount initially lost.

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JAMA Network Open Study Evaluates Which Patients Are More Likely To Discontinue Obesity Medications

Patients without insurance coverage for GLP-1 drugs face unique challenges in staying on these treatments, so their inclusion in research on adherence is essential.

WeightControl.com Interview with:
Patricia Rodriguez PhD MPH
Principal Applied Scientist
Truveta Research

Ty J. Gluckman, MD, MHA
Center for Cardiovascular Analytics
Research and Data Science (CARDS)
Providence Heart Institute
Providence Health System
Portland, Oregon

Ezekiel J. Emanuel, MD, PhD
Healthcare Transformation Institute
Department of Medical Ethics and Health Policy
Perelman School of Medicine
University of Pennsylvania, Philadelphia

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

Response: “Millions of Americans could benefit from GLP-1s, but clinical trials suggest that patients need to stay on these drugs to experience sustained benefits. We were interested in using data from patients across the country to understand whether patients are staying on these drugs, and what barriers may exist to continued use.

We looked at about 125,000 patients who started GLP-1 medications and found that a majority of patients stop taking them within one year. About 65% without type 2 diabetes (T2D) stopped within one year, compared with 47% of those with T2D.

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GLP-1 Receptor Agonists Found Effective for Weight Loss Among Adults Without Diabetes

Since there is a lack of head-to-head trials on these agents, future research should explore their comparative efficacy (e.g. semaglutide vs. tirzepatide vs. retatrutide).

WeightControl.com Interview with:

Areesha Moiz BSc
Centre of Clinical Epidemiology, Lady Davis Institute
Jewish General Hospital, and Division of Experimental Medicine
McGill University, Montreal, Quebec, Canada
Division of Experimental Medicine
McGill University

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

Response: GLP-1 receptor agonists have been used for type 2 diabetes management for almost two decades. Trials conducted in this patient population also showed some weight loss effects, leading to them being investigated in patients with overweight or obesity and without diabetes. With all the recent buzz around Ozempic (semaglutide) these past few years, we were interested in seeing what other agents in this class of drugs were out there, how they performed for weight loss, and how safe they were.

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Healthy Diet May Help With Pain Management, Regardless of Person’s Size

Fhe study found that diet quality could affect pain differently in men and women. Women who consumed a higher quality diet reported lower pain and had better physical function. This effect was less pronounced in men.

WeightControl.com Interview with:
Dr. Alison M Hill | PhD, APD, RNutr, MDiet, BAppSci (Human Movement) Hons.
Senior Lecturer in Nutrition
UniSA: Clinical and Health Sciences
Alliance for Research in Exercise, Nutrition and Activity (ARENA)
University of South Australia

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

Response: Chronic pain is a common and disabling health problem, estimated to affect 20-30% of people worldwide. Those who experience chronic pain often have a higher weight compared to the general population. Food choices that influence the overall quality of a person’s diet may contribute to an individual’s pain by affecting their weight or triggering bodily processes such as inflammation.

This study of Australian adults explored whether diet was directly linked to pain, and if factors like weight, or body fat, impacted this relationship. Additionally, the study looked at differences between men and women as chronic pain is more prevalent in women.

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