Internal Medicine
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)
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
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
EASL Clinical Practice Guidelines on acute-on-chronic liver failure
27 Jun, 2023 | 14:00h | UTCEASL Clinical Practice Guidelines on acute-on-chronic liver failure – Journal of Hepatology
Commentary on Twitter
?NEW@EASLnews Clinical Practice Guidelines on acute-on-chronic liver failure
Available here: https://t.co/GCNg1AIX9X pic.twitter.com/aKd0DUJBkL
— Journal of Hepatology (@JHepatology) June 24, 2023
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)
SR | Medically assisted hydration in palliative care: uncertain effects on quality of life and survival
27 Jun, 2023 | 13:47h | UTCSummary: The Cochrane Review analyzed Randomized Controlled Trials (RCTs) to evaluate the impact of Medically Assisted Hydration (MAH) on the Quality of Life (QoL) and survival of adults receiving palliative care. A total of four studies involving 422 participants, all diagnosed with advanced cancer, were considered. Two studies compared MAH with placebo, and two compared it with standard care.
The primary outcome was QoL, assessed through validated scales, with survival and adverse events being secondary outcomes. Mean differences (MD) and risk ratios (RR) were calculated for continuous and dichotomous outcomes, respectively. However, results were inconclusive due to a very low certainty of evidence. Hence, it is unclear whether MAH improves QoL, prolongs survival, or leads to adverse events when compared to placebo or standard care.
The findings are only applicable to inpatients with advanced cancer at the end of life and do not transfer to other adults in palliative care with non-cancer, dementia, or neurodegenerative diseases, or those with an extended prognosis. The lack of high-quality evidence leaves clinicians to make decisions based on perceived benefits and harms for individual circumstances.
Article: Medically assisted hydration for adults receiving palliative care – Cochrane Library
Review | Hypertension management in patients with cardiovascular comorbidities
27 Jun, 2023 | 13:39h | UTCHypertension management in patients with cardiovascular comorbidities – European Heart Journal
Commentary on Twitter
Hypertension management in patients with cardiovascular comorbidities. A State-of-the-Art review just published in #EHJ.@escardio @ESC_Journals #CardioTwitter #hypertensionhttps://t.co/esgOEkxlta pic.twitter.com/xDRHSWn6sZ
— EHJ Editor-in-Chief (@ehj_ed) June 21, 2023
Review | Renal thrombotic microangiopathy
27 Jun, 2023 | 13:34h | UTCRenal Thrombotic Microangiopathy: A Review – American Journal of Kidney Diseases
Commentary on Twitter
Renal Thrombotic Microangiopathy: A Review https://t.co/YabUm18t4q (FREE)@CPQMD @ReichHeather @UofTNephrology pic.twitter.com/Y9rSnuTFBo
— AJKD (@AJKDonline) June 24, 2023
Global, regional, and national burden of diabetes from 1990 to 2021, with projections of prevalence to 2050
26 Jun, 2023 | 01:00h | UTCSummary: This systematic review analyzed the global burden of diabetes, including trends, projections, and attributions to risk factors. It considered data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD), covering 204 countries and territories.
In 2021, an estimated 529 million people worldwide were living with diabetes. Regionally, the highest rates were observed in North Africa, the Middle East, and Oceania. Type 2 diabetes accounted for 96% of diabetes cases and 95.4% of diabetes DALYs (disability-adjusted life-years). More than half of global type 2 diabetes DALYs were attributable to high body mass index (BMI).
Predictions suggest that more than 1.31 billion people will have diabetes by 2050, with high prevalence rates in North Africa, the Middle East, and Latin America. The study notes the ongoing challenge of preventing and controlling type 2 diabetes, largely driven by increasing obesity. An understanding of disparities in risk profiles and disease burdens can inform strategies to control diabetes risk factors.
Editorial: Diabetes: a defining disease of the 21st century – The Lancet
News Release: Global diabetes cases to soar from 529 million to 1.3 billion by 2050 – Institute for Health Metrics and Evaluation
Commentary on Twitter (thread – click for more)
Today: More than 529 million people across the globe have diabetes
In the next 30 years: 1.3 billion people are projected to have diabetes
https://t.co/gh2O0K7RY0— Institute for Health Metrics and Evaluation (IHME) (@IHME_UW) June 22, 2023
Phase 2 RCT | Oral GLP-1 agonist Orforglipron outperforms dulaglutide and placebo in type 2 diabetes control
26 Jun, 2023 | 00:54h | UTCSummary: In a 26-week, phase 2, double-blind, randomized trial spanning multiple centers in the USA, Hungary, Poland, and Slovakia, researchers examined the efficacy and safety of orforglipron, a non-peptide GLP-1 receptor agonist. The sample comprised 383 adults aged 18 and older with type 2 diabetes treated with diet and exercise, with or without metformin, and with a glycated hemoglobin (HbA1c) of 7.0–10.5%.
The study’s primary efficacy outcome revealed that orforglipron achieved a significantly higher mean reduction in HbA1c compared to both the placebo and dulaglutide (-2.10% vs -0.43% and -1.10%, respectively). Furthermore, orforglipron induced a change in mean body weight at week 26 of -10.1 kg, outperforming both the placebo and dulaglutide. Adverse events mostly encompassed mild to moderate gastrointestinal issues.
The study concluded that orforglipron at doses of 12 mg or higher could potentially serve as an effective alternative to injectable GLP-1 receptor agonists and oral semaglutide, for type 2 diabetes treatment. While the drug’s safety profile was consistent with other GLP-1 receptor agonists, there is a need for larger confirmatory studies and dose regimen optimization.
Article: Efficacy and safety of oral orforglipron in patients with type 2 diabetes: a multicentre, randomised, dose-response, phase 2 study – The Lancet (link to abstract – $ for full-text)
Commentary: Orforglipron Shows Promise as Weight Loss, Diabetes Agent in Phase 2 Trials – HCP Live
Phase 2 RCT | Comparative study on CagriSema, Semaglutide, and Cagrilintide in type 2 diabetes
26 Jun, 2023 | 00:52h | UTCSummary: The study, a 32-week multicentre, randomized, double-blind, phase 2 trial, evaluated the combined effect of cagrilintide and semaglutide (CagriSema) on individuals with type 2 diabetes. 92 adults with type 2 diabetes and a BMI of 27 kg/m2 or higher were randomly assigned to one of three treatment groups: CagriSema, semaglutide, or cagrilintide.
The results indicated that the mean reduction in HbA1c was more pronounced with CagriSema than cagrilintide, but not semaglutide. The CagriSema group also showed greater weight loss versus both semaglutide and cagrilintide. In terms of safety, the most common adverse events were mild to moderate gastrointestinal events, with no fatal adverse events reported.
These findings suggest that CagriSema presents as a viable treatment option for type 2 diabetes, offering significant benefits in terms of weight loss and glycemic control. A potential limitation is the short duration of the study, which may not account for long-term effects and safety of the intervention. The authors conclude that these results support further investigation of CagriSema in larger, longer phase 3 trials.
Article: Efficacy and safety of co-administered once-weekly cagrilintide 2·4 mg with once-weekly semaglutide 2·4 mg in type 2 diabetes: a multicentre, randomised, double-blind, active-controlled, phase 2 trial – The Lancet (link to abstract – $ for full-text)
Secondary analysis of a RCT | Bempedoic acid reduces CV events in statin-intolerant patients with high CV risk
26 Jun, 2023 | 00:49h | UTCSummary: This secondary analysis of a Randomized Clinical Trial (RCT) evaluated the efficacy of bempedoic acid in primary prevention of cardiovascular events among statin-intolerant patients at high cardiovascular risk. From a total of 13,970 participants, 4206 met the criteria for primary prevention and were analyzed in this study. Those allocated to receive bempedoic acid showed a significant reduction in major cardiovascular events, reflected in a hazard ratio of 0.70.
The average age of this patient cohort was 68 years, and most participants (66%) were diagnosed with diabetes. Treatment with bempedoic acid also led to a significant 21.3% reduction in low-density lipoprotein cholesterol (LDL-C) levels and a 21.5% decrease in high-sensitivity C-reactive protein levels, suggesting improved cardiovascular health.
This study underscores the potential benefits of lipid-modulating therapy for primary prevention in high-risk patients, who are often undertreated. However, it is important to note the inherent limitations of this secondary analysis. The analysis was performed on a subgroup within a larger clinical trial, which could potentially lead to false-positive findings due to multiple testing. Furthermore, the results may not generalize to younger populations, those with lower pretreatment LDL-C levels, those without diabetes, or those with a lower baseline cardiovascular risk.
Article: Bempedoic Acid for Primary Prevention of Cardiovascular Events in Statin-Intolerant Patients – JAMA (free for a limited period)
Editorial: Bempedoic Acid for High-Risk Primary Prevention of Cardiovascular Disease: Not a Statin Substitute but a Good Plan B – JAMA (free for a limited period)
See also: Visual Abstract
Commentary: Study Suggests Bempedoic Acid Could Find Role in Primary Prevention – HCP Live
Original Study: RCT | Bempedoic acid shows modest reduction in cardiovascular events for statin-intolerant patients
Cohort Study | Association of preterm birth with increased asthma and COPD risk in adulthood
26 Jun, 2023 | 00:45h | UTCSummary: This population-based register study investigated the correlation between gestational ages (GA) and obstructive airway diseases like asthma and chronic obstructive pulmonary disease (COPD) in adulthood. The study used registry data from 706,717 individuals born between 1987-1998 in Finland (4.8% preterm), and 1,669,528 individuals born from 1967-1999 in Norway (5.0% preterm). The study observed care episodes of asthma and COPD using nationwide healthcare registers.
The results showed an increased risk of obstructive airway disease in adulthood for those born at <28 or 28–31 completed weeks of gestation. Even after adjustments, the risk remained 2-3 times greater compared to those who were born full term (at 39-41 completed weeks). Additionally, the risk for COPD at age 30–50 was significantly higher for those born at <28 weeks, with an odds ratio (OR) of 7.44. The study also identified that bronchopulmonary dysplasia (BPD) in infancy increased the odds of obstructive airway disease for those born at <28 and 28–31 weeks.
These findings suggest that preterm birth is a notable risk factor for asthma and COPD in adulthood, and this risk was observed across all gestational ages before full term. The study recommends diagnostic vigilance for adults born very preterm presenting with respiratory symptoms. However, the researchers also noted the potential limitations of using registry data, which might include residual confounding from unmeasured confounders and lack of data on certain prenatal or early life factors.
Article: Preterm birth and asthma and COPD in adulthood: a nationwide register study from two Nordic countries – European Respiratory Journal (free for a limited period)
Commentary on Twitter
In this population-based study of 2.4 million people from Finland and Norway, adults born preterm were at higher risk for asthma and COPD at ages 18–50 years. The risks were observed across all gestational ages before full term in a dose-response manner. https://t.co/bGsAOrwAxV pic.twitter.com/WmCoc6cPu2
— ERS publications (@ERSpublications) June 22, 2023
Review | Differentiating infection, colonization, and sterile inflammation in critical illness
26 Jun, 2023 | 00:41h | UTCDifferentiating infection, colonisation, and sterile inflammation in critical illness: the emerging role of host-response profiling – Intensive Care Medicine (free for a limited period)
Commentary on Twitter
Infection, colonisation, sterile inflammation in critical illness?
? current approaches to distinguishing
? host–pathogen interactions
? techniques to characterise host response
? challenges/limitations of host‑response diagnostics
#FOAMcc @yourICM
?️https://t.co/d3vhgrt3ZE pic.twitter.com/eDFiinMvSp— Intensive Care Medicine (@yourICM) June 22, 2023
Review | Evaluation and management of diabetes-related foot infections
23 Jun, 2023 | 13:36h | UTCEvaluation and Management of Diabetes-related Foot Infections – Clinical Infectious Diseases
Related: Guideline Series | Prevention and management of diabetes-related foot disease
Guideline | Management of adrenal incidentalomas
23 Jun, 2023 | 13:33h | UTCRelated:
Investigation and assessment of adrenal incidentalomas – Clinical Medicine Journal
#377 Adrenal Incidentalomas with Dr. William Young – The Curbsiders
Cohort Study | Real-world data links valproate, antipsychotics to higher diabetes risk in bipolar disorder
23 Jun, 2023 | 13:32h | UTC
Retrospective study | Increasing prevalence and severity of carbapenem-resistant Klebsiella Pneumoniae in ICUs
23 Jun, 2023 | 13:25h | UTC
Cohort Study | Increased depression risk observed in first two years of oral contraceptive use
23 Jun, 2023 | 13:19h | UTCNews Release: New study links contraceptive pills and depression – Uppsala University
Commentary: Depression Risk May Rise During First Two Years of Oral Contraceptive Use – Psychiatric News Alert
Commentary on Twitter
Population-based cohort study of oral #contraceptive use and risk of #depression suggests that the use of OCs, particularly during the first 2 years, increases the risk of depression.https://t.co/spWuqCMKfW@therese_johans #mentalhealth #epidemiology pic.twitter.com/xMO0yiqPvt
— Epidemiology & Psychiatric Sciences (@EpiPsychSci) June 19, 2023
Scientific Advisory | Expedited CT scanning with iodinated contrast when necessary favored over renal concerns in emergencies
22 Jun, 2023 | 15:19h | UTCRelated:
Radiographic Contrast Media and the Kidney – Clinical Journal of the American Society of Nephrology
Contrast-Associated Acute Kidney Injury – Journal of Clinical Medicine
Choosing Wisely | Recommendations for advance care planning
22 Jun, 2023 | 15:18h | UTCSee complete lists of low-value practices: Choosing Wisely U.S. / Choosing Wisely UK / Choosing Wisely Australia AND Choosing Wisely Canada
Cohort Study | Risk and outcome of infective endocarditis in streptococcal bloodstream infections according to streptococcal species
22 Jun, 2023 | 15:09h | UTC