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[News Release] RCT | Semaglutide 2.4 mg reduces cardiovascular risk by 20% in adults with CVD & obesity

9 Aug, 2023 | 15:40h | UTC

Novo Nordisk A/S: Semaglutide 2.4 mg reduces the risk of major adverse cardiovascular events by 20% in adults with overweight or obesity in the SELECT trial – Novo Nordisk


SELECT: Semaglutide Cuts CV Events in Adults With Overweight or Obesity – TCTMD

Expert reaction to Novo Nordisk press release announcing the headline results from their SELECT cardiovascular outcomes semaglutide trial – Science Media Centre

Related: Role of Glucagon‐Like Peptide‐1 Receptor Agonists in Achieving Weight Loss and Improving Cardiovascular Outcomes in People With Overweight and Obesity – Journal of the American Heart Association


WHO updates guidelines on fats and carbohydrates

28 Jul, 2023 | 14:25h | UTC

News Release: WHO updates guidelines on fats and carbohydrates – World Health Organization


Saturated fatty acid and trans-fatty acid intake for adults and children: WHO guideline – World Health Organization

Total fat intake for the prevention of unhealthy weight gain in adults and children: WHO guideline – World Health Organization

Carbohydrate intake for adults and children: WHO guideline – World Health Organization


Commentary on Twitter (thread – click for more)


RCT | Liraglutide aids weight management in patients with suboptimal weight loss post metabolic surgery

28 Jul, 2023 | 14:05h | UTC

Safety and Efficacy of Liraglutide, 3.0 mg, Once Daily vs Placebo in Patients With Poor Weight Loss Following Metabolic Surgery: The BARI-OPTIMISE Randomized Clinical Trial – JAMA Surgery

See also: Visual Abstract


Scientific Statement | Addressing childhood obesity to reduce adult CV risk through lifestyle

27 Jul, 2023 | 13:03h | UTC

Lifestyle interventions to change trajectories of obesity-related cardiovascular risk from childhood onset to manifestation in adulthood: a joint scientific statement of the task force for childhood health of the European Association of Preventive Cardiology and the European Childhood Obesity Group – European Journal of Preventive Cardiology

News 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 | UTC

Body mass index and all-cause mortality in a 21st century U.S. population: A National Health Interview Survey analysis – PLOS One

News 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 | UTC

News Release: Aspartame hazard and risk assessment results released – World Health Organization


Expert reaction to IARC and JEFCA summary on aspartame – Science Media Centre

Does artificial sweetener aspartame really cause cancer? What the WHO listing means for your diet soft drink habit – The Conversation

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 | UTC

Time-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


RCT | Intermittent fasting plus early time-restricted eating vs. calorie restriction and standard care in adults at risk of type 2 DM

RCT | Time-restricted eating not more effective than daily calorie restriction for managing nonalcoholic fatty liver disease

Health effects of the time-restricted eating in adults with obesity: A systematic review and meta-analysis – Frontiers in Nutrition

Time-restricted eating and exercise training improve HbA1c and body composition in women with overweight/obesity: A randomized controlled trial – Cell Metabolism

Effectiveness of Early Time-Restricted Eating for Weight Loss, Fat Loss, and Cardiometabolic Health in Adults With Obesity: A Randomized Clinical Trial – JAMA Internal Medicine

Effects of Intermittent Fasting in Human Compared to a Non-intervention Diet and Caloric Restriction: A Meta-Analysis of Randomized Controlled Trials – Frontiers in Nutrition

Time-Restricted Eating: Integrating The What With The When – Advances in Nutrition

Calorie Restriction with or without Time-Restricted Eating in Weight Loss- New England Journal of Medicine

Intermittent Fasting and Obesity-Related Health Outcomes: An Umbrella Review of Meta-analyses of Randomized Clinical Trials – JAMA Network Open


RCT | Weekly Tirzepatide outperforms placebo in weight management for type 2 diabetes patients

7 Jul, 2023 | 16:24h | UTC

Tirzepatide 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 | UTC

American Society of Anesthesiologists Consensus-Based Guidance on Preoperative Management of Patients (Adults and Children) on Glucagon-Like Peptide-1 (GLP-1) Receptor Agonists – American Society of Anesthesiologists

Commentary: 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 | UTC

Summary: 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.

Article: Low glycaemic index or low glycaemic load diets for people with overweight or obesity – Cochrane Library

Summary: Do low glycaemic index or low glycaemic load diets help people with overweight or obesity to lose weight? – Cochrane Library


Phase 2 RCT | Triple-hormone-receptor (GIP, GLP-1, and glucagon) agonist Retatrutide substantially reduces body weight in obesity

28 Jun, 2023 | 13:23h | UTC

Summary: 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


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 | UTC

Summary: 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 | UTC

Summary: 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 | UTC

Summary: 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 | UTC

Summary: 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 | UTC

Adiposity 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

Role of Glucagon‐Like Peptide‐1 Receptor Agonists in Achieving Weight Loss and Improving Cardiovascular Outcomes in People With Overweight and Obesity – Journal of the American Heart Association


Cohort Study | Weight change and risk of obesity-related complications

15 Jun, 2023 | 14:53h | UTC

Weight change and risk of obesity-related complications: A retrospective population-based cohort study of a UK primary care database – Diabetes, Obesity and Metabolism


Commentary from the author on Twitter


M-A | Clinical outcomes associated with drugs for obesity and overweight

12 Jun, 2023 | 13:24h | UTC

Clinical outcomes associated with drugs for obesity and overweight: A systematic review and network meta-analysis of randomized controlled trials – Diabetes, Obesity and Metabolism


RCT | Tirzepatide outperforms insulin glargine in HbA1c reduction and weight loss in type 2 diabetes

6 Jun, 2023 | 14:39h | UTC

Tirzepatide versus insulin glargine as second-line or third-line therapy in type 2 diabetes in the Asia-Pacific region: the SURPASS-AP-Combo trial – Nature Medicine


Commentary on Twitter


Review | Child and adolescent obesity

30 May, 2023 | 11:45h | UTC

Child and adolescent obesity – Nature Reviews Disease Primers (if the link is paywalled, try this one)


Commentary on Twitter


Clinical Trial Update | Mesenteric defects closure in bariatric surgery cuts reoperation rate due to bowel obstruction

29 May, 2023 | 10:49h | UTC

Long-term Safety and Efficacy of Closure of Mesenteric Defects in Laparoscopic Gastric Bypass Surgery: A Randomized Clinical Trial – JAMA Surgery (link to abstract – $ for full-text)

See also: Visual Abstract


Opinion Video | Questioning the reliability of nutrition science

23 May, 2023 | 13:02h | UTC

Nutrition science is entirely unreliable | Don’t trust the New York Times Well section – By Dr Vinay Prasad


WHO advises not to use non-sugar sweeteners for weight control in newly released guideline

16 May, 2023 | 15:04h | UTC

News Release: WHO advises not to use non-sugar sweeteners for weight control in newly released guideline – World Health Organization

WHO Guideline: Use of non-sugar sweeteners – World Health Organization

Meta-Analysis: Health effects of the use of non-sugar sweeteners – World Health Organization


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