Endocrinology (all articles)
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
RCT | Weekly insulin Icodec proves effective in glucose control in insulin-naive type 2 diabetes patients
3 Jul, 2023 | 14:32h | UTCSummary: The ONWARDS 3 randomized clinical trial studied the efficacy of once-weekly insulin icodec in comparison to once-daily insulin degludec for glucose control in insulin-naive type 2 diabetes patients. The double-masked, double-dummy trial was conducted from March 2021 to June 2022 across 92 sites in 11 countries, enrolling 588 adults with type 2 diabetes. The participants were randomly divided into two groups: 294 receiving once-weekly icodec and daily placebo, and 294 receiving daily degludec and weekly placebo.
The primary endpoint was the change in Hemoglobin A1c (HbA1c) from baseline to week 26. Insulin icodec showed a noninferior HbA1c change from the baseline (-1.6 percentage points) compared to insulin degludec (-1.4 percentage points) and demonstrated confirmed statistical superiority. However, the trial showed a higher rate of combined level 2 (clinically significant) or level 3 (severe) hypoglycemic events in the insulin icodec group than in the insulin degludec group, despite the overall low rates in both groups. There was no significant difference in weight changes between the two groups.
The study concluded that once-weekly insulin icodec demonstrated superior HbA1c reduction compared to once-daily degludec after 26 weeks of treatment in insulin-naive type 2 diabetes patients. The convenience of once-weekly administration should be considered against the slightly higher absolute risk of hypoglycemia. The study’s limitations include its short duration (26 weeks) and a lack of data on sustained effects, patient-reported outcomes, and continuous glucose monitoring.
Article: Once-Weekly Insulin Icodec vs Once-Daily Insulin Degludec in Adults With Insulin-Naive Type 2 Diabetes: The ONWARDS 3 Randomized Clinical Trial – JAMA (link to abstract – $ for full-text)
See also: Visual Abstract
Related Study: Weekly Icodec versus Daily Glargine U100 in Type 2 Diabetes without Previous Insulin – New England Journal of Medicine (link to abstract – $ for full-text)
Open-label RCT | Weekly insulin Icodec proves noninferior to daily Glargine in type 2 diabetes
3 Jul, 2023 | 14:23h | UTCWeekly Icodec versus Daily Glargine U100 in Type 2 Diabetes without Previous Insulin – New England Journal of Medicine (link to abstract – $ for full-text)
Related Study: Once-Weekly Insulin Icodec vs Once-Daily Insulin Degludec in Adults With Insulin-Naive Type 2 Diabetes: The ONWARDS 3 Randomized Clinical Trial – JAMA (free for a limited period)
Phase 2 RCT | FGF21 analogue Pegozafermin treatment leads to improvement in NASH fibrosis
30 Jun, 2023 | 14:58h | UTCSummary: In a phase 2b, multicenter, double-blind, randomized, placebo-controlled trial, the fibroblast growth factor 21 (FGF21) analogue pegozafermin was examined for its efficacy and safety in treating patients with biopsy-confirmed noncirrhotic nonalcoholic steatohepatitis (NASH). A total of 222 patients with moderate or severe fibrosis (stage F2 or F3) were assigned to receive either subcutaneous pegozafermin at varying doses or a placebo. The primary endpoints were an improvement in fibrosis and resolution of NASH without worsening of fibrosis at 24 weeks.
The results showed that a larger percentage of patients receiving pegozafermin met the criteria for fibrosis improvement and NASH resolution compared to those receiving placebo. The most significant improvements were observed in the 44-mg pegozafermin group, with 27% showing fibrosis improvement and 26% meeting NASH resolution criteria, compared to 7% and 2% in the placebo group, respectively. Adverse events were mainly gastrointestinal and included nausea and diarrhea. These findings support the progression of pegozafermin into phase 3 development.
Article: Randomized, Controlled Trial of the FGF21 Analogue Pegozafermin in NASH – New England Journal of Medicine (link to abstract – $ for full-text)
Commentary on Twitter
Late breaking at #EASLCongress: In this phase 2b, placebo-controlled trial involving patients with nonalcoholic steatohepatitis, pegozafermin, a long-acting glycopegylated FGF21 analogue, reduced fibrosis at 24 weeks. Full results by @drloomba et al.: https://t.co/mfRRrV2yX2
— NEJM (@NEJM) June 24, 2023
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.
M-A | Effects of SGLT-2 inhibitors on adipose tissue distribution in patients with type 2 diabetes mellitus
30 Jun, 2023 | 14:47h | UTC
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)
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 | 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)
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
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
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
SCORE2-Diabetes | 10-year cardiovascular risk estimation in type 2 diabetes in Europe
22 Jun, 2023 | 14:57h | UTC
Commentary on Twitter
SCORE2-Diabetes: 10-year cardiovascular risk estimation in type 2 diabetes in Europe https://t.co/lkPTzqk0Kg @escardio #EHJ #ESCYoung pic.twitter.com/5TxesSwN1t
— European Society of Cardiology Journals (@ESC_Journals) June 14, 2023
The foot in diabetes – a reminder of an ever-present risk
21 Jun, 2023 | 13:10h | UTCThe foot in diabetes – a reminder of an ever-present risk – Clinical Medicine Journal
Related: Guideline Series | Prevention and management of diabetes-related foot disease
Scientific Statement | Hormones and aging
20 Jun, 2023 | 12:45h | UTCNews Release: Endocrine Society Scientific Statement distinguishes normal aging from endocrine disease – Endocrine Society
RCT | Testosterone replacement does not appear to increase cardiovascular events in hypogonadal men at high risk
19 Jun, 2023 | 14:13h | UTCCardiovascular Safety of Testosterone-Replacement Therapy – New England Journal of Medicine (link to abstract – $ for full-text)
Commentary on Twitter
Presented today at #ENDO2023: In the TRAVERSE study, a randomized trial involving men with hypogonadism and preexisting or a risk of cardiovascular disease, testosterone therapy was noninferior to placebo with respect to major adverse cardiac events. https://t.co/V3FTTsOLd1
— NEJM (@NEJM) June 16, 2023
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
RCT | No significant kidney outcome differences observed across glucose-lowering medications in T2D patients
15 Jun, 2023 | 15:02h | UTCComparative Effects of Glucose-Lowering Medications on Kidney Outcomes in Type 2 Diabetes: The GRADE Randomized Clinical Trial – JAMA Internal Medicine (link to abstract – $ for full-text)
See also: Visual Abstract
Commentaries:
No differences found in effects of secondary diabetes drugs on kidney outcomes – ACP Diabetes
Do glucose-lowering medications have different effects on kidney outcomes? – News Medical