Dexamethasone Increases Diabetes Complications but Still Saves Lives

via MedScape | 12 November 2021 | Dexamethasone Increases Diabetes Complications but Still Saves Lives

Research presented earlier this month at The Society for Endocrinology’s annual conference, SfE BES 2021, suggests that  when dexamethasone is prescribed to hospitalised COVID-19 patients with diabetes may increase their risk of developing steroid-induced dysglycaemia but it does not prevent them from experiencing the life-saving benefits of the drug, suggests a real-world UK analysis.

Data on more than 2250 patients treated in the first and second waves of the pandemic showed that, in patients with diabetes, dexamethasone increased the risk of dysglycaemia more than 20-fold.

However, patients with dexamethasone-associated complications did not have an increased risk of death, and overall the drug was shown to reduce the risk of admission to intensive care or death within 30 days of admission by 56 per cent (Source: MedScape).

The full news story is available from MedScape

Dapagliflozin in patients with cardiometabolic risk factors hospitalised with COVID-19 (DARE-19): a randomised, double-blind, placebo-controlled, phase 3 trial

Kosiborod, M.N. et al | 2021 | Dapagliflozin in patients with cardiometabolic risk factors hospitalised with COVID-19 (DARE-19): a randomised, double-blind, placebo-controlled, phase 3 trial | The Lancet Diabetes & Endocrinology | DOI:https://doi.org/10.1016/S2213-8587(21)00180-7

The DARE-19 trial has evaluated the efficacy and safety of dapagliflozin in patients who had at least one cardiometabolic risk factor, such as hypertension and type 2 diabetes among others, and who were hospitalised with COVID-19.

At screening, 636 patients (50·9 per cent ) had type 2 diabetes. The prespecified subgroup analyses for the primary outcome of prevention and recovery are shown in, and were generally consistent with the main findings, including in patients with and without diabetes, although there was heterogeneity noted by sex. Diabetic ketoacidosis was reported in two patients in the dapagliflozin group both of whom had type 2 diabetes at baseline; these events were non-severe and resolved after study medication discontinuation.

To the authors’ knowledge, DARE-19 is the first, large randomised controlled trial to evaluate efficacy and safety of SGLT2 inhibitors in patients hospitalised with COVID-19 and has implications for clinical practice and future research. Dapagliflozin did not significantly reduce the proportion of patients with organ dysfunction or death or who experienced improved recovery. Although we observed numerically fewer events of organ dysfunction or death in patients who received dapagliflozin as compared with placebo, this difference was not statistically significant, and might not be generalisable to other populations. Importantly, dapagliflozin was well tolerated in one of the highest risk (with respect to organ failure and death) patient populations ever to be treated with SGLT2 inhibitors.


Implications of all the available evidence

Their study shows that dapagliflozin was well tolerated, with no new safety concerns identified in this acutely ill patient population. Therefore, for patients already receiving SGLT2 inhibitors before a COVID-19 diagnosis, our findings support continuation of this treatment, as long as patients are monitored. Because SGLT2 inhibitors do not have a direct anti-viral effect on SARS-CoV2, our findings (although not conclusive) suggest a need for future trials to determine whether dapagliflozin might provide organ protection in non-COVID-19 hospitalised patients at high risk for progressing to critical illness (Source: Kosiborod et al, 2021).

Primary paper Dapagliflozin in patients with cardiometabolic risk factors hospitalised with COVID-19 (DARE-19): a randomised, double-blind, placebo-controlled, phase 3 trial

The state of diabetes treatment coverage in 55 low-income and middle-income countries

Flood, D. et al | 2021| The state of diabetes treatment coverage in 55 low-income and middle-income countries: a cross-sectional study of nationally representative, individual-level data in 680 102 adults | The Lancet Healthy Longevity | https://www.thelancet.com/journals/lanhl/article/PIIS2666-7568(21)00089-1/fulltext

This cross-sectional cohort study is the largest assessment of comprehensive diabetes treatment using individual-level data from nationally representative samples of adults across low-income and middle-income countries (LMICs) of diverse income groups and geographical regions. 

Key points:

  1. Less than one in ten people with diabetes in LMICs receive comprehensive diabetes treatment as recommended by WHO; scaling up the capacity of health systems to deliver treatment not only to lower glucose but also to address cardiovascular disease risk factors, such as hypertension and high cholesterol, are urgent global diabetes priorities.
  2. The authors make cross-country estimates of diabetes treatment that could be used by health systems in LMICs to benchmark current and future performance
  3. They report individual characteristics such as young age and lower body-mass index that are associated with low coverage of diabetes treatment; these individual-level findings can be used by health systems to direct care to underserved groups.

The authors findings suggest that improving access to comprehensive treatment not only to lower glucose but also to address cardiovascular disease risk factors such as hypertension and elevated cholesterol are global diabetes priorities.

Paper available in full from The Lancet Healthy Longevity

NHS spends around £3bn a year on ‘avoidable’ treatment for diabetes

ITV | September 2019 | NHS spends around £3bn a year on ‘avoidable’ treatment for diabetes

An analysis of hospital treatment in 2017/18 highlights that approximately £5.5bn each year is spent on treatment of diabetes, of this an estimated £3bn is on ‘potentially avoidable’ treatment. The authors of the research explain that this equates to around one-tenth of the NHS budget; compared to people without diabetes, the average annual cost of planned care was over twice as high for those with Type 2 diabetes and the average cost of emergency care was three times higher, once age was taken into account.

the-level-of-sugar-in-the-blood-3310318_640

Study author, Dr Adrian Heald from Salford Royal Hospital, said: “People with diabetes are admitted to hospital more often, especially as emergencies, and stay on average longer as inpatients.

“These increased hospital costs, 40% of which come from non-elective and emergency care, are three times higher than the current costs of diabetes medication.

“Improved management of diabetes by GPs and diabetes specialist care teams could improve the health of people with diabetes and substantially reduce the level of hospital care and costs.” (Source: ITV News)

The team’s finding will be presented this week at the European Association for the study of Diabetes (EASD)  annual meeting in Barcelona.

Read the full story from ITV News

See also:

BT NHS spends around £3bn a year on ‘avoidable’ treatment for diabetes

 

NICE: Dapagliflozin with insulin for treating type 1 diabetes

NICE | August 2019| Dapagliflozin with insulin for treating type 1 diabetes

Today (28 August 2019) has published  final guidance on an innovative treatment for type 1 diabetes. Dapagliflozin is the first licenced oral add-on therapy to insulin in type 1 diabetes

Dapagliflozin (brand name Forxiga) with insulin is available on the NHS. It is a possible treatment for type 1 diabetes in adults with a body mass index (BMI) of at least 27 kg/m2, when insulin alone does not control blood sugar levels well enough, if:

  • you are on insulin doses of more than 5 units per kilogram of body weight per day and
  • you have done a structured education programme that includes information about diabetic ketoacidosis, and
  • treatment is started and supervised by a consultant physician specialising in endocrinology and diabetes.

Further details are available from NICE

Effect of lorcaserin on prevention and remission of type 2 diabetes in overweight and obese patients (CAMELLIA-TIMI 61)

Background

 

There is a direct relationship between bodyweight and risk of diabetes. Lorcaserin, a selective serotonin 2C receptor agonist that suppresses appetite, has been shown to facilitate sustained weight loss in obese or overweight patients. We aimed to evaluate the long-term effects of lorcaserin on diabetes prevention and remission.

 

Methods

 

In this randomised, double-blind, placebo-controlled trial done in eight countries, we recruited overweight or obese patients (body-mass index ≥27 kg/m 2) with or at high risk for atherosclerotic vascular disease. Eligible patients were aged 40 years or older; patients at high risk for atherosclerotic vascular disease had to be aged 50 years or older with diabetes and at least one other risk factor. Patients were randomly assigned to receive either lorcaserin (10 mg twice daily) or matching placebo. Additionally, all patients had access to a standardised weight management programme based on lifestyle modification. The prespecified primary metabolic efficacy endpoint of time to incident diabetes was assessed in patients with prediabetes at baseline. The prespecified secondary outcomes for efficacy were incident diabetes in all patients without diabetes, achievement of normoglycaemia in patients with prediabetes, and change in glycated haemoglobin (HbA 1c) in patients with diabetes. Hypoglycaemia was a prespecified safety outcome. Analysis was by intention to treat, using Cox proportional hazard models for time-to-event analyses. This trial is registered with ClinicalTrials.gov, number NCT02019264.

 

Findings

 

Between Feb 7, 2014, and Nov 20, 2015, 12 000 patients were randomly assigned to lorcaserin or placebo (6000 patients in each group) and followed up for a median of 3·3 years (IQR 3·0–3·5). At baseline, 6816 patients (56·8%) had diabetes, 3991 (33·3%) prediabetes, and 1193 (9·9%) normoglycaemia. At 1 year, patients treated with lorcaserin had a net weight loss beyond placebo of 2·6 kg  for those with diabetes, 2·8 kg  for those with prediabetes, and 3·3 kg (2·6–4·0) for those with normoglycaemia (p<0·0001 for all analyses). Lorcaserin reduced the risk of incident diabetes by 19% in patients with prediabetes  and by 23% in patients without diabetes . Lorcaserin resulted in a non-significant increase in the rate of achievement of normoglycaemia in patients with prediabetes . In patients with diabetes, lorcaserin resulted in a reduction of 0·33%  in HbA 1c compared with placebo at 1 year from a mean baseline of 53 mmol/mol . In patients with diabetes at baseline, severe hypoglycaemia with serious complications was rare, but more common with lorcaserin.

 

Interpretation

 

Lorcaserin decreases risk for incident diabetes, induces remission of hyperglycaemia, and reduces the risk of microvascular complications in obese and overweight patients, supporting the role of lorcaserin as an adjunct to lifestyle modification for chronic management of weight and metabolic health.

 

Funding

 

Eisai.

 

Reference
VOLUME 392, ISSUE 10161, P2269-2279, NOVEMBER 24, 2018

Common diabetes drug may not reduce risk of death, according to new research

Imperial College London | April 2018 | Diabetes drug may not reduce risk of death

A new paper published in the Journal of the American Medical Association (JAMA),   studied three types of diabetes treatment to compare hwo they reduced mortality for people with type 2 diabetes.  These are sodium-glucose cotransporter 2 (SGLT-2) inhibitors, glucagon-like peptide 1 (GLP-1) agonists, and dipeptidyl peptidase 4 (DPP-4) inhibitors. Previous research findings indicate these treatments are currently prescribed to at least one in three people with type 2 diabetes (via Imperial College London).

Question  How do sodium-glucose cotransporter 2 (SGLT-2) inhibitors, glucagon-like peptide 1 (GLP-1) agonists, and dipeptidyl peptidase 4 (DPP-4) inhibitors compare in reducing mortality and cardiovascular events in patients with type 2 diabetes?

Findings  In this network meta-analysis that includes 236 trials with 176 310 participants, the use of SGLT-2 inhibitors or GLP-1 agonists was significantly associated with lower all-cause mortality compared with the control groups (placebo or no treatment) (hazard ratio [HR], 0.80, and HR, 0.88, respectively) and with DPP-4 inhibitors (HR, 0.78, and HR, 0.86, respectively).

Meaning  In patients with type 2 diabetes, the use of SGLT-2 inhibitors or GLP-1 agonists was associated with better mortality outcomes than DPP-4 inhibitors

test-214185_1280

Abstract 

Importance  The comparative clinical efficacy of sodium-glucose cotransporter 2 (SGLT-2) inhibitors, glucagon-like peptide 1 (GLP-1) agonists, and dipeptidyl peptidase 4 (DPP-4) inhibitors for treatment of type 2 diabetes is unknown.

Objective  To compare the efficacies of SGLT-2 inhibitors, GLP-1 agonists, and DPP-4 inhibitors on mortality and cardiovascular end points using network meta-analysis.

Data Sources  MEDLINE, Embase, Cochrane Library Central Register of Controlled Trials, and published meta-analyses from inception through October 11, 2017.

Study Selection  Randomized clinical trials enrolling participants with type 2 diabetes and a follow-up of at least 12 weeks were included, for which SGLT-2 inhibitors, GLP-1 agonists, and DPP-4 inhibitors were compared with either each other or placebo or no treatment.

Data Extraction and Synthesis  Data were screened by 1 investigator and extracted in duplicate by 2 investigators. A Bayesian hierarchical network meta-analysis was performed.

Main Outcomes and Measures  The primary outcome: all-cause mortality; secondary outcomes: cardiovascular (CV) mortality, heart failure (HF) events, myocardial infarction (MI), unstable angina, and stroke; safety end points: adverse events and hypoglycemia.

Results  This network meta-analysis of 236 trials randomizing 176 310 participants found SGLT-2 inhibitors (absolute risk difference [RD], −1.0%; hazard ratio [HR], 0.80 [95% credible interval {CrI}, 0.71 to 0.89]) and GLP-1 agonists (absolute RD, −0.6%; HR, 0.88 [95% CrI, 0.81 to 0.94]) were associated with significantly lower all-cause mortality than the control groups. SGLT-2 inhibitors (absolute RD, −0.9%; HR, 0.78 [95% CrI, 0.68 to 0.90]) and GLP-1 agonists (absolute RD, −0.5%; HR, 0.86 [95% CrI, 0.77 to 0.96]) were associated with lower mortality than were DPP-4 inhibitors. DPP-4 inhibitors were not significantly associated with lower all-cause mortality (absolute RD, 0.1%; HR, 1.02 [95% CrI, 0.94 to 1.11]) than were the control groups. SGLT-2 inhibitors (absolute RD, −0.8%; HR, 0.79 [95% CrI, 0.69 to 0.91]) and GLP-1 agonists (absolute RD, −0.5%; HR, 0.85 [95% CrI, 0.77 to 0.94]) were significantly associated with lower CV mortality than were the control groups. SGLT-2 inhibitors were significantly associated with lower rates of HF events (absolute RD, −1.1%; HR, 0.62 [95% CrI, 0.54 to 0.72]) and MI (absolute RD, −0.6%; HR, 0.86 [95% CrI, 0.77 to 0.97]) than were the control groups. GLP-1 agonists were associated with a higher risk of adverse events leading to trial withdrawal than were SGLT-2 inhibitors (absolute RD, 5.8%; HR, 1.80 [95% CrI, 1.44 to 2.25]) and DPP-4 inhibitors (absolute RD, 3.1%; HR, 1.93 [95% CrI, 1.59 to 2.35]).

Conclusions and Relevance  In this network meta-analysis, the use of SGLT-2 inhibitors or GLP-1 agonists was associated with lower mortality than DPP-4 inhibitors or placebo or no treatment. Use of DPP-4 inhibitors was not associated with lower mortality than placebo or no treatment.
Full reference: Zheng,  S.L., et al |2018 | Association Between Use of Sodium-Glucose Cotransporter 2 Inhibitors, Glucagon-like Peptide 1 Agonists, and Dipeptidyl Peptidase 4 Inhibitors With All-Cause Mortality in Patients With Type 2 Diabetes A Systematic Review and Meta-analysis| JAMA | 319 |Vol. 15 | p. 1580–1591. doi:10.1001/jama.2018.3024

The full article is available here from JAMA

Imperial College’s news feature is here 

A new mechanism for regulating glucose uptake by the liver has implications for type 2 diabetes and its treatment

Japanese researchers have  identified a sirtuin enzyme (Sirt2) as a key player in regulating hepatic glucokinase | via ScienceDaily

diabetes-2994808_1920

Abnormalities in glucose uptake by the liver (or hepatic glucose uptake; HGU) cause elevations in blood glucose levels following meals, a state that is known as postprandial hyperglycemia.

Such abnormalities are observed in obesity and type 2 diabetes and result in an increased risk of cardiovascular complications. Although the exact mechanism of HGU impairment is unknown, there is evidence that it is mediated by abnormal regulation of the enzyme hepatic glucokinase and the glucokinase regulatory protein (GKRP).

This new  research shows that diminished hepatic Sirt2 activity impairs HGU in obese diabetic mice.  Through modifying the glucokinase regulatory protein (GKRP,)  the researchers suggest that this mechanism offers a potential therapeutic target for type 2 diabetes.

Full story at Science Daily

The full text article is available from Nature Communications

Full reference:  Watanabe, H., et al.| Sirt2 facilitates hepatic glucose uptake by deacetylating glucokinase regulatory protein| Nature Communications | Vol. 9 no. 30 | 2018