Daily Archives: June 28, 2023
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 | Bulevirtide reduces HDV RNA and ALT levels in chronic hepatitis D patients
28 Jun, 2023 | 13:20h | UTCSummary: This randomized phase 3 trial evaluated the efficacy of bulevirtide, an inhibitor of HDV entry into hepatocytes, in patients with chronic hepatitis D. Patients were randomized to receive either 2 mg or 10 mg of bulevirtide daily for 144 weeks, or no treatment for 48 weeks followed by 10 mg bulevirtide daily for 96 weeks. The study involved 150 patients, 49 in the 2-mg group, 50 in the 10-mg group, and 51 in the control group.
After 48 weeks of treatment, 45% and 48% of patients in the 2-mg and 10-mg groups respectively achieved the primary end point of undetectable HDV RNA level or a decrease of at least 2 log10 IU per milliliter from baseline, and normalization of ALT level. Only 2% in the control group reached the primary endpoint. ALT levels normalized in 51% and 56% of patients in the 2-mg and 10-mg groups respectively, a significant difference from the 12% normalization in the control group. Notably, loss of HBsAg did not occur by week 48 in the bulevirtide groups. No serious adverse events related to the treatment were reported, though side effects including headache, pruritus, and fatigue were more common in the bulevirtide groups.
These results demonstrate the effectiveness of bulevirtide in reducing HDV RNA and ALT levels in patients with chronic hepatitis D. However, the absence of HBsAg loss in bulevirtide groups raises questions about its long-term implications.
Article: A Phase 3, Randomized Trial of Bulevirtide in Chronic Hepatitis D – New England Journal of Medicine (link to abstract – $ for full-text)
Commentary on Twitter
Presented today at #EASLCongress: In a randomized trial, 48 weeks of treatment with bulevirtide, which inhibits hepatitis D virus entry into hepatocytes, reduced HDV RNA and alanine aminotransferase levels in patients with chronic hepatitis D. https://t.co/Q8RNZFbQlQ
— NEJM (@NEJM) June 22, 2023
Perspective | Psychedelic treatments for mental health conditions pose challenges for informed consent
28 Jun, 2023 | 13:17h | UTC
Perspective | Ensuring ethical postprogression therapy for patients in randomized trial control arms
28 Jun, 2023 | 13:16h | UTC
Commentary on Twitter
Ensuring Ethical Postprogression Therapy for Patients in RCT Arms
"Patients participating in clinical trials make significant sacrifices, and in return the academic and clinical communities owe them optimal treatment after progression"@JCO_ASCO https://t.co/2dv2rky2WN pic.twitter.com/rQfRx3T4Ii
— Yakup Ergün (@dr_yakupergun) June 22, 2023
Cohort Study | Younger adults with modest kidney function reductions show increased risk of adverse outcomes
28 Jun, 2023 | 13:14h | UTCSummary: This study was a retrospective, population-based cohort study exploring the implications of modest reductions in estimated glomerular filtration rate (eGFR) in young adults. The study was conducted on 8.7 million adult residents aged 18-65 years in Ontario, Canada, with no history of kidney disease. Data was collected from January 2008 to March 2021.
The research revealed that 18.0% of those aged 18-39, 18.8% of those aged 40-49, and 17.0% of those aged 50-65 had modestly reduced eGFR measurements specific to their age group. Adverse outcomes, including all-cause mortality, cardiovascular events, and kidney failure, were consistently higher by hazard ratio and incidence for ages 18-39 across all eGFR categories, compared to older groups. The hazard ratio for modest reductions (eGFR 70-80 mL/min/1.73m2) was found to be 1.42 for ages 18-39 years.
The findings suggest that even modest reductions in kidney function can significantly impact younger adults, necessitating frequent monitoring of kidney function in this demographic to prevent chronic kidney disease and its complications. It is noteworthy, however, that potential limitations of this study include possible misclassification of comorbidities, unmeasured confounding, and a lack of insight into the mechanism of these modest eGFR reductions.
News Release: Even a modest reduction in kidney function increases health risks in young adults – University of Ottawa
RCT | Total breast reconstruction with autologous fat transfer using an expansion device vs implants in patients with breast cancer
28 Jun, 2023 | 13:12h | UTCEffect of Total Breast Reconstruction With Autologous Fat Transfer Using an Expansion Device vs Implants on Quality of Life Among Patients With Breast Cancer: A Randomized Clinical Trial – JAMA Surgery (link to abstract – $ for full-text)
See also: Visual Abstract
Author Interview: Effect of Breast Reconstruction With Autologous Fat Transfer vs Implants on Quality of Life – JAMA
Podcast | Antiplatelets, anticoagulation for coronary artery disease and atrial fibrillation
28 Jun, 2023 | 13:11h | UTC#400 Antiplatelets, Anticoagulation for Coronary Artery Disease and Afib – The Curbsiders
Podcast | Wisely ordering autoantibodies
28 Jun, 2023 | 13:09h | UTC#399 Wisely Ordering Autoantibodies – ACP IM2023 – The Curbsiders
KDOQI US commentary on the 2021 KDIGO clinical practice guideline for the management of glomerular diseases
28 Jun, 2023 | 13:07h | UTCOriginal Guideline: KDIGO 2021 clinical practice guideline for the management of glomerular diseases – Kidney Disease: Improving Global Outcomes