Obesity
Cohort Study: GLP1 receptor agonist use not associated with significant increase in thyroid cancer risk – The BMJ
25 May, 2024 | 19:51h | UTCA large Scandinavian cohort study investigated the association between glucagon-like peptide 1 (GLP1) receptor agonist use and thyroid cancer risk in Denmark, Norway, and Sweden from 2007 to 2021. The study compared 145,410 patients treated with GLP1 receptor agonists to 291,667 patients treated with dipeptidyl peptidase 4 (DPP4) inhibitors and included an additional analysis with sodium-glucose cotransporter 2 (SGLT2) inhibitors. Results showed no significant increase in thyroid cancer risk among GLP1 users over a mean follow-up of 3.9 years, with a hazard ratio of 0.93 (95% CI, 0.66 to 1.31) compared to DPP4 inhibitor users. The study utilized nationwide cancer registers and employed an active-comparator, new user design to minimize confounding, using Cox regression models adjusted by propensity score weighting. The findings suggest that while small risk increases cannot be definitively ruled out, the use of GLP1 receptor agonists does not substantially elevate thyroid cancer risk.
Reference (link to free full-text):
RCT: Effects of combined time-restricted eating and high-intensity functional training on body composition and cardiometabolic health in women with obesity – PLOS One
7 May, 2024 | 15:28h | UTCThis randomized clinical trial investigated the effects of time-restricted eating (TRE) and high-intensity functional training (HIFT), both separately and in combination, on body composition and cardiometabolic health in inactive women with obesity. Sixty-four participants were assigned to three groups: TRE alone, HIFT alone, and both TRE and HIFT (TRE-HIFT). Over 12 weeks, the TRE-HIFT group showed the most significant improvements in waist and hip circumference, fat mass, total cholesterol, triglyceride levels, insulin sensitivity, and blood glucose levels compared to the other groups. Weight and BMI reductions were also more substantial in the TRE-HIFT group than in the HIFT-only group. Furthermore, while all groups exhibited improvements, those combining both interventions experienced more pronounced changes in cardiometabolic parameters, suggesting the potential of integrated lifestyle interventions for enhancing health outcomes in this population.
Reference (link to free full-text):
Pooled Analysis: Semaglutide improves symptoms and reduces weight in obesity-related heart failure with preserved ejection fraction
28 Apr, 2024 | 16:33h | UTCThis pooled analysis of the STEP-HFpEF and STEP-HFpEF DM randomized trials assessed the efficacy of semaglutide in 1,145 participants with obesity-related heart failure and preserved ejection fraction, across 129 research sites globally. Participants, who had a BMI of at least 30 kg/m2 and varied cardiovascular conditions, were administered 2.4 mg of semaglutide weekly for 52 weeks. Semaglutide significantly improved heart failure-related symptoms (7.5 points increase in KCCQ-CSS), reduced body weight by 8.4%, and increased the 6-min walk distance by 17.1 meters, compared to placebo. The treatment also demonstrated safety, with fewer serious adverse events than the placebo group. These benefits were consistent across various subgroups, confirming semaglutide’s potential as a treatment in this patient population.
Reference (link to abstract – $ for full-text):
Pooled Analysis: Changes in prevalence of underweight and obesity from 1990 to 2022 in 200 countries
27 Apr, 2024 | 16:02h | UTCStudy Design and Population:
This pooled analysis utilized data from 3,663 population-representative studies involving 222 million participants to assess trends in underweight, thinness, and obesity. The study separated its analysis between adults (aged ≥20 years) and school-aged children and adolescents (aged 5–19 years) across 200 countries from 1990 to 2022. Bayesian hierarchical models were employed to estimate trends in different BMI categories.
Main Findings:
The findings indicate significant geographical and demographic variations in the prevalence of underweight and obesity. While the combined prevalence of underweight and obesity decreased in a minority of countries, it increased significantly in the majority, particularly in island nations, the Middle East, and North Africa. The study also found that obesity rates have surpassed underweight rates in the vast majority of countries by 2022.
Implications for Practice:
The increasing prevalence of obesity alongside persistent underweight and thinness issues underscores the need for a dual-focused public health approach. Strategies should prioritize not only the reduction of obesity through healthy eating and physical activity but also address undernutrition by improving access to nutritious foods, especially in regions like south Asia and parts of Africa where underweight remains prevalent.
Phase 2 RCT: Low-dose aspirin significantly reduces hepatic fat in MASLD patients without cirrhosis
20 Mar, 2024 | 17:48h | UTCStudy Design and Population: This phase 2, randomized, double-blind, placebo-controlled clinical trial was carried out over six months at a single hospital in Boston, Massachusetts. The study included 80 participants aged 18 to 70 years diagnosed with metabolic dysfunction–associated steatotic liver disease (MASLD) but without cirrhosis. Participants were randomly assigned to receive either 81 mg of daily aspirin (n=40) or placebo (n=40).
Main Findings: The trial revealed that aspirin significantly reduced the mean absolute change in hepatic fat content by -10.2% compared with placebo, as measured by proton magnetic resonance spectroscopy (MRS), with a statistically significant difference (P=0.009). Furthermore, aspirin treatment notably decreased relative hepatic fat content, increased the proportion of patients achieving a 30% or greater reduction in hepatic fat, and reduced both absolute and relative hepatic fat content as assessed by magnetic resonance imaging proton density fat fraction (MRI-PDFF). Adverse events were mostly minor, with upper respiratory infections and arthralgias being the most common.
Implications for Practice: These findings suggest that low-dose aspirin may be an effective intervention for reducing liver fat in adults with MASLD without cirrhosis, potentially offering a simple, accessible treatment option. However, the results are preliminary and call for further confirmation in larger, more diverse populations. The study underscores the importance of considering low-dose aspirin as part of management strategies for MASLD, pending further research.
Reference
Simon TG et al. (2024). Randomized Clinical Trial: Low-Dose Aspirin Significantly Reduces Hepatic Fat in MASLD Patients Without Cirrhosis. JAMA, 331(11), 920-929. DOI: 10.1001/jama.2024.1215. Access the study here: [Link]
[News Release] RCT | Semaglutide 2.4 mg reduces cardiovascular risk by 20% in adults with CVD & obesity
9 Aug, 2023 | 15:40h | UTCCommentaries:
SELECT: Semaglutide Cuts CV Events in Adults With Overweight or Obesity – TCTMD
WHO updates guidelines on fats and carbohydrates
28 Jul, 2023 | 14:25h | UTCNews Release: WHO updates guidelines on fats and carbohydrates – World Health Organization
Guidelines:
Carbohydrate intake for adults and children: WHO guideline – World Health Organization
Commentary on Twitter (thread – click for more)
Avoid #TransFats! Trans fats are found in
?️ baked & fried foods,
?️ pre-packaged snacks,
?️ meat & dairy foods from animals such as cows or sheep,
?️ processed foods.Limit your trans fats intake to less than 1% of total energy intake ?https://t.co/vCZlOtUeLj #HealthyDiets pic.twitter.com/l0ErFXvO4Q
— World Health Organization (WHO) (@WHO) July 17, 2023
RCT | Liraglutide aids weight management in patients with suboptimal weight loss post metabolic surgery
28 Jul, 2023 | 14:05h | UTCSee also: Visual Abstract
Scientific Statement | Addressing childhood obesity to reduce adult CV risk through lifestyle
27 Jul, 2023 | 13:03h | UTCNews Release: How to stop obese children having heart disease in adulthood – European Society of Cardiology
Podcast | Obesity medicine, GLP1 agonists, weight loss management tools and tips
27 Jul, 2023 | 12:55h | UTC#405 Obesity Medicine, GLP1 agonists, Weight Loss Management Tools and Tips – The Curbsiders
Cohort Study | BMI of 25.0–29.9 not linked with higher mortality in 21st century U.S. adults
25 Jul, 2023 | 13:58h | UTCNews Release: No increase in mortality for most overweight people, study finds – PLOS
Commentary: Expert reaction to study looking at BMI and all-cause mortality – Science Media Centre
IARC, WHO agency, identifies aspartame as potentially carcinogenic but probably safe within established acceptable daily intake
18 Jul, 2023 | 13:58h | UTCNews Release: Aspartame hazard and risk assessment results released – World Health Organization
Commentaries:
Expert reaction to IARC and JEFCA summary on aspartame – Science Media Centre
Aspartame Hazard and Risk Assessment Results Released by IARC and JECFA – The ASCO Post
RCT | No significant difference in weight loss between intermittent fasting and calorie restriction
10 Jul, 2023 | 13:56h | UTCTime-Restricted Eating Without Calorie Counting for Weight Loss in a Racially Diverse Population: A Randomized Controlled Trial – Annals of Internal Medicine (link to abstract – $ for full-text)
News Release: Intermittent fasting and traditional calorie counting shown to be about equal for weight loss – American College of Physicians
Commentary: Intermittent fasting and calorie counting about equal for weight loss – new study – The Conversation
Related:
Time-Restricted Eating: Integrating The What With The When – Advances in Nutrition
RCT | Weekly Tirzepatide outperforms placebo in weight management for type 2 diabetes patients
7 Jul, 2023 | 16:24h | UTCTirzepatide once weekly for the treatment of obesity in people with type 2 diabetes (SURMOUNT-2): a double-blind, randomised, multicentre, placebo-controlled, phase 3 trial – The Lancet (link to abstract – $ for full-text)
Commentary: Tirzepatide triumphs in significant weight reduction for people with type 2 diabetes – News Medical
ASA Consensus Guidance | Preoperative management of patients on GLP-1 agonists
5 Jul, 2023 | 01:17h | UTCCommentary: Anesthesiologists Say Ozempic, Wegovy Should Be Halted Prior to Surgery – HealthDay
SR | Little to no impact of low glycemic index/glycemic load diets on weight loss in overweight or obese individuals
30 Jun, 2023 | 14:54h | UTCSummary: This systematic review examined the impact of low glycaemic index or load (GI/GL) diets on weight loss in overweight or obese individuals, analyzing data from 10 randomized controlled trials (RCTs), with 1,210 participants. The main outcomes included changes in body weight, body mass index (BMI), adverse events, health-related quality of life, and mortality. The study showed that low GI/GL diets probably result in little to no difference in body weight and BMI changes compared to higher GI/GL diets or other diets. The evidence suggests a lack of effect on all main outcomes and the possible positive influence on mood remains uncertain.
The studies included in this review had a small sample size with a moderate to very low certainty of evidence. This suggests more well-structured studies with larger sample sizes are needed for firmer conclusions. Limitations of this review included the risk of bias, as many of the studies did not adopt objective outcome measurements and some had a high degree of loss to follow-up. Furthermore, the researchers recommend that future studies focus on diverse demographic groups and include participants from low- and middle-income countries.
Phase 2 RCT | Triple-hormone-receptor (GIP, GLP-1, and glucagon) agonist Retatrutide substantially reduces body weight in obesity
28 Jun, 2023 | 13:23h | UTCSummary: This Phase 2, double-blind, randomized, placebo-controlled trial evaluated the efficacy and safety of Retatrutide, a triple-hormone-receptor agonist of GIP, GLP-1, and glucagon, for obesity treatment. The study recruited 338 adults, predominantly male, with a Body Mass Index (BMI) of 30 or higher, or 27 to 30 with at least one weight-related condition. Participants were administered subcutaneous Retatrutide at varying doses or a placebo, once weekly for 48 weeks.
The findings indicate a dose-dependent weight loss efficacy for Retatrutide. At 24 weeks, Retatrutide users exhibited a mean body weight decrease ranging from 7.2% (1 mg dose) to 17.5% (12 mg dose), compared to a 1.6% reduction in the placebo group. This effect was even more pronounced at 48 weeks, with changes ranging from 8.7% (1 mg dose) to a striking 24.2% (12 mg dose), contrasted with a 2.1% reduction in the placebo group. Adverse events, primarily gastrointestinal, were common with Retatrutide, reported by 73 to 94% of patients, and were dose-related.
Retatrutide demonstrated substantial body weight reduction in adults with obesity, with a side effects profile similar to existing GLP-1 and GIP–GLP-1 receptor agonists. These promising results warrant further investigation through a Phase 3 trial to further ascertain the safety and efficacy of Retatrutide in obesity treatment.
Article: Triple–Hormone-Receptor Agonist Retatrutide for Obesity — A Phase 2 Trial – New England Journal of Medicine (link to abstract – $ for full-text)
Commentary on Twitter
Late breaking at #ADA23: In this trial involving participants with obesity, 48 weeks of treatment with retatrutide, an agonist of the GIP, GLP-1, and GCG receptors, resulted in substantial reductions in body weight. https://t.co/jNL1GNna0l
— NEJM (@NEJM) June 26, 2023
Phase 2 RCT | Triple receptor agonist (GIP, GLP-1 and glucagon) Retatrutide shows promising results in obese patients with T2DM
28 Jun, 2023 | 13:21h | UTCSummary: A Phase 2 Randomized Clinical Trial (RCT) was conducted to investigate the efficacy and safety of Retatrutide, a glucose-dependent insulinotropic polypeptide (GIP), GLP-1, and glucagon receptor agonist, in patients with type 2 diabetes. The study involved 281 adults aged between 18 and 75 years with type 2 diabetes. These patients, with a mean HbA1c level of 8·3%, a mean BMI of 35·0 kg/m², and a mean body weight of 98·2 kg, were randomized to Retatrutide at various doses, Dulaglutide 1.5 mg, and placebo. Patients were treated with diet and exercise alone or a stable dose of metformin for at least three months prior to the study.
The primary outcomes revealed that at 24 weeks, participants who received the higher doses of Retatrutide demonstrated substantial improvements in HbA1c compared to the placebo group and those who received Dulaglutide. Specifically, for the highest-dose Retatrutide group (12 mg), HbA1c level was reduced by an average of 2.02%, which was significantly greater compared to a reduction of 0.01% in the placebo group and 1.41% in the Dulaglutide group.
Regarding body weight, at 36 weeks, participants receiving the different doses of Retatrutide showed a dose-dependent decrease: 3.19% for the 0.5 mg group, 7.92% for the 4 mg escalation group, 10.37% for the 4 mg group, 16.81% for the 8 mg slow escalation group, 16.34% for the 8 mg fast escalation group, and 16.94% for the 12 mg escalation group. This was significantly higher compared to the 3.00% weight loss in the placebo group and the 2.02% loss with 1.5 mg Dulaglutide.
Mild-to-moderate gastrointestinal adverse events were reported among 35% of the participants in the Retatrutide groups, similar to those in the Dulaglutide group, and no severe hypoglycemia or deaths were reported.
The implications of these findings suggest that Retatrutide provides clinically meaningful improvements in glycaemic control and bodyweight reduction with a safety profile consistent with GLP-1 receptor agonists and GIP and GLP-1 receptor agonists. Limitations of the study include limitation of this study is the relatively short duration of the trial and small sample size. Long-term effects and safety of Retatrutide remain to be evaluated in further studies.
Article: Retatrutide, a GIP, GLP-1 and glucagon receptor agonist, for people with type 2 diabetes: a randomised, double-blind, placebo and active-controlled, parallel-group, phase 2 trial conducted in the USA – The Lancet (link to abstract – $ for full-text)
RCT | Oral Semaglutide at 25mg and 50mg improves glycemic control in overweight T2DM patients compared to standard 14mg dose
27 Jun, 2023 | 13:58h | UTCSummary: The study was a global, multicenter, randomized, double-blind, phase 3b trial involving 1606 adults with inadequately controlled type 2 diabetes. The mean HbA1c in the study population was 9.0% and the mean BMI was 33.8 kg/m2. Participants were assigned to receive either 14mg, 25mg, or 50mg of once-daily oral semaglutide for 68 weeks. The trial aimed to investigate the effectiveness of a new formulation of semaglutide at higher investigational doses against the standard 14mg dose.
The primary endpoint was the change in glycated hemoglobin (HbA1c) levels from baseline to week 52. Results showed that at week 52, changes in HbA1c levels were significantly more substantial with the 25mg (-1.8 percentage points) and 50mg (-2.0 percentage points) doses compared to the 14mg dose (-1.5 percentage points). During the trial, ten deaths occurred, but none were considered treatment-related. No new safety concerns were identified, though adverse events, primarily mild to moderate gastrointestinal disorders, were slightly more frequent in the 25mg and 50mg groups.
The study limitations include a relatively short exposure to the higher doses due to the up to 16 weeks of dose-escalation period, non-adjustable doses due to masking requirements, and a cohort predominantly of White ethnicity, considering the high prevalence of type 2 diabetes in other racial groups. The study was unable to assess differences in efficacy and tolerability between the 25mg and 50mg doses, raising the question of whether the 50mg dosage is necessary if similar effects can be achieved with the 25mg dose.
The implications for further research highlight the need for real-world studies to investigate the clinical impact and safety of these higher doses of oral semaglutide. The superior glycemic control and bodyweight loss with oral semaglutide 25mg and 50mg suggest that these higher doses might help individualize treatment goals and intensify treatment by increasing the dose of a single oral agent. Future studies could consider comparing the 25mg and 50mg doses more directly to determine the most effective and tolerable dose for patients.
Article: Efficacy and safety of once-daily oral semaglutide 25 mg and 50 mg compared with 14 mg in adults with type 2 diabetes (PIONEER PLUS): a multicentre, randomised, phase 3b trial – The Lancet (free registration required)
RCT | Once-daily oral Semaglutide 50mg outperforms placebo in obesity treatment
27 Jun, 2023 | 13:57h | UTCSummary: The referenced study is a phase 3, superiority, randomized, double-blind, placebo-controlled trial that investigated the effectiveness of oral semaglutide 50mg in treating overweight and obese adults without type 2 diabetes. The trial was conducted in 50 outpatient clinics across Asia, Europe, and North America, with a total of 667 participants randomly allocated to receive either the treatment or a placebo.
The primary outcome measured was the percentage change in bodyweight from baseline to week 68. Results showed a significant reduction in bodyweight among participants receiving semaglutide – a mean change of -15.1% compared to -2.4% for placebo recipients. Additionally, a higher percentage of semaglutide recipients achieved weight reductions of at least 5%, 10%, 15%, and 20% compared to placebo recipients.
However, it’s important to note that adverse events were more frequently observed in the semaglutide group. Specifically, 80% of participants receiving oral semaglutide 50 mg experienced gastrointestinal adverse events, mostly mild to moderate, compared to 46% in the placebo group. This highlights the need for careful patient monitoring during treatment.
The findings indicate that oral semaglutide 50mg, when taken once daily, can lead to a clinically meaningful decrease in bodyweight among overweight and obese adults without type 2 diabetes. Despite the higher occurrence of gastrointestinal adverse events, the significant weight loss potential positions oral semaglutide as a promising treatment option. Further research is recommended to establish long-term safety and efficacy.
Article: Oral semaglutide 50 mg taken once per day in adults with overweight or obesity (OASIS 1): a randomised, double-blind, placebo-controlled, phase 3 trial – The Lancet (link to abstract – $ for full-text)
Phase 2 RCT | Orforglipron, an oral GLP-1 receptor agonist, significantly reduces weight in adults with obesity
26 Jun, 2023 | 00:58h | UTCSummary: The article reports a phase 2, randomized, double-blind trial investigating the efficacy of the GLP-1 receptor agonist, orforglipron, as an oral weight loss treatment for adults with obesity or overweight plus at least one weight-related condition. The study involved 272 participants, who were administered orforglipron at varying doses or a placebo over a 36-week period.
The key findings of the study indicated significant weight reduction in individuals who were administered orforglipron. At 26 weeks, weight changes in the orforglipron group ranged from -8.6% to -12.6% compared to -2.0% in the placebo group. At 36 weeks, these figures were -9.4% to -14.7% for the orforglipron group and -2.3% for the placebo group. Furthermore, 46-75% of orforglipron recipients experienced a weight reduction of at least 10% by week 36, compared to 9% in the placebo group.
Improvements were also observed in all prespecified weight-related and cardiometabolic measures among orforglipron users. However, the treatment was associated with some mild to moderate gastrointestinal side effects, leading to discontinuation in 10-17% of participants. The safety profile was in line with other GLP-1 receptor agonists. These findings suggest that orforglipron could potentially be an effective oral treatment for weight reduction in adults with obesity, though further research is needed to corroborate these results and assess long-term effects.
Article: Daily Oral GLP-1 Receptor Agonist Orforglipron for Adults with Obesity – New England Journal of Medicine (link to abstract – $ for full-text)
Cohort Study | Adiposity impacts cancer risk differently in males and females
22 Jun, 2023 | 15:08h | UTCAdiposity and sex-specific cancer risk – Cancer Cell
News Release: Cancer has an obesity-related risk factor, and it depends on sex and cancer type – Cell Press
Review | Role of GLP1 receptor agonists in achieving weight loss and improving CV outcomes in people with overweight and obesity
19 Jun, 2023 | 13:40h | UTC
Cohort Study | Weight change and risk of obesity-related complications
15 Jun, 2023 | 14:53h | UTC
Commentary from the author on Twitter
Our paper showing association of weight loss on risk of developing 13 obesity-related complications
Weight loss benefit dependent on weight loss magnitude & initial BMI-weight gain associated with a similar risk ⬆️
4 patterns of association identifiedhttps://t.co/7iQCCsIJ3x pic.twitter.com/xVVLruS6Jg
— Prof Kamlesh Khunti (@kamleshkhunti) June 8, 2023
M-A | Clinical outcomes associated with drugs for obesity and overweight
12 Jun, 2023 | 13:24h | UTC