Diabetes
RCT: No difference in ICU length of stay or 90-day mortality between tight and liberal glucose control
2 Oct, 2023 | 11:25h | UTCStudy Design and Population: This randomized controlled trial assessed the effects of tight versus liberal glucose control on the length of ICU stay in critically ill patients. A total of 9,230 patients were included, with 4,622 in the liberal-control group (insulin initiation when blood glucose levels exceeded 215 mg/dL) and 4,608 in the tight-control group (blood glucose targeted between 80 and 110 mg/dL). In both groups, parenteral nutrition was withheld during the first week of ICU admission. The primary endpoint was the duration of ICU stay, and 90-day mortality served as a key safety outcome.
Main Findings: No significant differences were observed in the primary endpoint, the length of ICU stay, between the two groups (hazard ratio 1.00; 95% CI, 0.96 to 1.04; P=0.94). The 90-day mortality rates were also similar (10.1% in the liberal-control group vs. 10.5% in the tight-control group, P=0.51). Incidences of severe hypoglycemia were low and statistically similar in both groups (1.0% in the tight-control group vs. 0.7% in the liberal-control group). Secondary outcomes, including new infections and the duration of respiratory and hemodynamic support, showed no significant differences. However, lower incidences of severe acute kidney injury and cholestatic liver dysfunction were observed in the tight-control group.
Implications & Limitations: The study supports existing evidence that tight glucose control doesn’t provide substantial benefits in reducing ICU stay duration or mortality. This suggests that a more liberal approach to glucose control may be preferable in most ICU settings, especially to minimize hypoglycemia risk. Key limitations of the study include its narrow focus on the absence of early parenteral nutrition, which could limit generalizability, and the inability to blind caregivers to treatment assignments. Future research should investigate the impact of tight glucose control in various patient subgroups and under different nutritional conditions.
Presented at ASRS Meeting | Studies link GLP-1 agonists to progression of diabetic retinopathy
11 Aug, 2023 | 15:38h | UTCStudies link GLP-1 agonists to progression of diabetic retinopathy – MDedge
Multinational Study | No correlation between Covid-19 and onset of type 1 diabetes in children
8 Aug, 2023 | 13:32h | UTC
Cohort Study | Habitual calcium supplementation linked to higher CVD incidence and mortality in diabetics
8 Aug, 2023 | 13:24h | UTCAssociations of Habitual Calcium Supplementation With Risk of Cardiovascular Disease and Mortality in Individuals With and Without Diabetes – Diabetes Care (link to abstract – $ for full-text)
Commentary on Twitter
Habitual Ca supplementation was associated with higher risks of CVD in diabetics but not non-diabetics, suggesting that diabetics may need to be cautious about the long-term use of Ca supplements. @ADA_Pubs
Read Here➡️https://t.co/wUBy6KJhaw pic.twitter.com/6FXmwBwnMS
— Diabetes Care, a research journal of the ADA ? (@DiabetesCareADA) July 28, 2023
Do-it-yourself automated insulin delivery: a health-care practitioner user’s guide
7 Aug, 2023 | 14:44h | UTC
Review | Diabetes of the exocrine pancreas: implications for pharmacological management
7 Aug, 2023 | 14:25h | UTCDiabetes of the Exocrine Pancreas: Implications for Pharmacological Management – Drugs
Cohort Study | Exploring the potential impact of artificial sweeteners on type 2 diabetes risk
28 Jul, 2023 | 14:07h | UTC
Cohort Study | More data suggests SGLT-2 inhibitors could reduce gout flares
26 Jul, 2023 | 13:24h | UTCComparative Effectiveness of Sodium–Glucose Cotransporter-2 Inhibitors for Recurrent Gout Flares and Gout-Primary Emergency Department Visits and Hospitalizations: A General Population Cohort Study – Annals of Internal Medicine (link to abstract – $ for full-text)
Commentaries:
SGLT-2 inhibitors reduced gout flares in patients with diabetes, gout – ACP Internist
SGLT2i Use Linked to Reduced Risk for Flare in Adults With Gout, T2D – HealthDay
SGLT2 inhibitors linked with fewer gout flares in diabetes – MDedge
Guideline | Laboratory analysis in the diagnosis and management of diabetes mellitus
21 Jul, 2023 | 13:50h | UTCExecutive Summary: Guidelines and Recommendations for Laboratory Analysis in the Diagnosis and Management of Diabetes Mellitus – Diabetes Care
Review | Painful diabetic peripheral neuropathy
20 Jul, 2023 | 10:53h | UTC
RCT | Metformin boosts effectiveness of lifestyle interventions for diabetes prevention in individuals with impaired glucose regulation
13 Jul, 2023 | 13:07h | UTCSafety and effectiveness of metformin plus lifestyle intervention compared with lifestyle intervention alone in preventing progression to diabetes in a Chinese population with impaired glucose regulation: a multicentre, open-label, randomised controlled trial – The Lancet Diabetes & Endocrinology (link to abstract – $ for full-text)
Related Study: Reduction in the Incidence of Type 2 Diabetes with Lifestyle Intervention or Metformin – New England Journal of Medicine (link to abstract – $ for full-text)
Single Arm Trial | Low-carbohydrate diet improves glycemic control in type 1 diabetes
13 Jul, 2023 | 13:04h | UTCRelated:
Management of Type 1 Diabetes With a Very Low–Carbohydrate Diet – Pediatrics (link to abstract – $ for full-text)
Lower carbohydrate diets for adults with type 2 diabetes – British Journal of Nutrition
Low carbohydrate diet: Insights from a general practice service in patients with type 2 diabetes
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
Review | Cardiovascular outcomes in patients with diabetes and kidney disease
7 Jul, 2023 | 16:13h | UTC
Review | Diabetes detection in women with gestational diabetes and polycystic ovarian syndrome
7 Jul, 2023 | 16:08h | UTCDiabetes detection in women with gestational diabetes and polycystic ovarian syndrome – The BMJ
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)
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 | 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