Medicine supply notification for GLP-1 receptor agonists in type 2 diabetes
The Department of Health and Social Care has released a notification regarding medicine supply for GLP-1 receptor agonists used to manage type 2 diabetes. It says there are very limited, intermittent supplies of all glucagon-like peptide-1 receptor agonists (GLP-1 RAs) licensed in the management of type 2 diabetes mellitus. Supply is not expected to return to normal until at least mid-2024.
The supply issues have been caused by an increase in demand for these products for licensed and off-label indications. Practitioners are asked to refer to the SPS Tool for Medicines Shortages for an up-to-date supply stock situation and clinical guidance on alternative treatment options.
This medicine supply notification, including further information for pharmacy teams, includes:
- Annex 1: Selecting Alternative Glucose Lowering Therapy for People with T2DM when GLP1-RAs are unavailable
- Annex 2: Quick reference guide for selecting oral antidiabetic therapy
- Annex 3: Oral Glucose Lowering Therapies by Class
- Annex 4 : GLP-1 RAs affected. The SPS Medicines Supply Tool will be updated for stock position of all GLP1 RAs.
The online Medicines Supply Tool, from the Department for Health and Social Care and NHS England, has up to date information about medicine supply issues. This can be found at: https://www.sps.nhs.uk/wp-login.php?redirect_to=https%3A%2F%2Fwww.sps.nhs.uk%2Fhome%2Ftools%2Fmedicines-supply-tool%2F&reauth=1.
New compound discovery has breakthrough potential for parasitic diseases
Scientists have discovered a new class of compound that is potentially active against trypanosome parasites that cause human African trypanosomiasis (sleeping sickness) and Chagas disease.
The findings were published in the journal Science and led by researchers at the University of Glasgow and Novartis Global Health (formerly Novartis Institutes for Tropical Diseases), revealing potent compounds discovered for the two separate types of trypanosomiases showed potential for development as new medicines for these diseases.
The study found that the compounds were able to cure a mouse model of sleeping sickness with a single dose and a short course of daily doses across 5 days cured Chagas disease in the same models.
The authors say sleeping sickness is a major disease that puts around 70 million people at risk in sub-Saharan African countries. It is caused by microscopic parasites of the species Trypanosoma brucei and transmitted by the tsetse fly (Glossina species), which is found only in sub-Saharan Africa. It can be fatal if inadequately treated. Around 7 million people are currently infected with Chagas disease, which can cause irreversible damage to the heart and digestive tract. According to the US Centers for Disease Control, efforts to reduce the incidence have led to a decrease in the number of annual cases. For the first time in 50 years, the number of reported cases fell under 10 000 in 2009. There are currently no drugs available that effectively cure Chagas disease, and for sleeping sickness, there have been some steps forward toward new therapies in recent years.
The researchers also showed in the study how the compounds, cyanotriazoles (CTs), kill parasites without adversely affecting host cells. They selectively bind to a parasite enzyme (topoisomerase II) that is essential for the replication and maintenance of DNA. By binding to and inhibiting this enzyme, the compounds introduce breaks in the DNA that kill off the parasites.
The Glasgow group – led by Professor Mike Barrett from the Wellcome Centre for Integrative Parasitology in the University School of Infection and Immunity – found that mechanism of action using a technique known as metabolomics, through the Glasgow Polyomics facility, which showed how DNA was being degraded in the cells. Parasites resistant to the drugs had changed their topoisomerase protein structure such that they no longer bound the drug.
The Novartis team, led by Srini Rao, worked out the three-dimensional structure of the trypanosome's topoisomerase, revealing how CTs bind to a particular part of the trypanosome's enzyme that is absent from the human version.
Professor Barrett said: ‘Compounds with this degree of potency, working through a newly discovered mechanism, represent a major breakthrough. If they are proven to be safe in humans and retain the levels of activity seen in mice, they could offer the first effective therapy of Chagas disease which afflicts millions of people in Latin America.’
Deucravacitinib for treating moderate to severe plaque psoriasis guidance
Evidence-based recommendations on deucravacitinib for treating moderate to severe plaque psoriasis in adults were published on 28 June by the National Institute for Health and Care Excellence (NICE).
Deucravacitinib is recommended as an option for treating moderate to severe plaque psoriasis in adults, only if:
- The Psoriasis Area and Severity Index (PASI) score is 10
- The condition has not responded to other systemic treatments, including ciclosporin, methotrexate and phototherapy, or these options are contraindicated or not tolerated
- The company provides deucravacitinib according to the commercial arrangement.
The guidance says, ‘Clinical trial evidence shows that deucravacitinib improves symptoms of plaque psoriasis compared with placebo and apremilast. Deucravacitinib was indirectly compared with apremilast, dimethyl fumarate and several systemic biological treatments.
‘The indirect comparison suggests it improves symptoms better than apremilast and dimethyl fumarate, and works as well as some biological treatments but not as well as others. The cost-effectiveness estimates for deucravacitinib compared with apremilast, dimethyl fumarate and most biological treatments are within the range that NICE normally considers an acceptable use of NHS resources. So, deucravacitinib is recommended. they and their NHS clinician consider it appropriate to stop.’
The guidance, TA907, Deucravacitinib for treating moderate to severe plaque psoriasis, can be found at: https://www.nice.org.uk/guidance/ta907/chapter/1-Recommendations
Newly developed scoring system can correctly predict suicide risk after self-harm
A new risk calculator based on key social, demographic and clinical factors can predict suicide risk in those who have self-harmed within 6–12 months, suggests research published in the open-access journal BMJ Mental Health.
Pending further validation, the Oxford Suicide Assessment Tool for Self-harm may help inform treatment decisions and the most effective targeting of resources, suggest the researchers.
The researchers used real-life data from Swedish population registries to devise a more accurate scoring system for risk prediction. A total of 53 172 people aged 10+ years who had sought emergency medical care after episodes of non-fatal self-harm, were split into two groups – one for the development of the new predictive scoring system and the other for its external validation.
The development group included 37 523 people: 267 (0.7%) died by suicide within 6 months; 391 did so within 12 months; and 540 (1.4%) took their own lives within 2 years. The validation group included 15 649 people: the corresponding figures were 108 (0.7%); 178 (just over 1%); and 251 (1.6%), respectively.
The researchers then assessed a range of potential factors associated with suicide risk within 12 months of the self-harm episode. These included demographic information, age, sex, medical history and treatment, mental health, history of self-harm, family psychiatric history, and substance misuse.
More than 10 outcomes per predictive factor were considered for development and more than 100 outcomes for validation.
Within the 2 years following an episode of self-harm around 1 in 70 people died by suicide, with around 1 in 100 in the 12 months following the self-harm episode. Among those who died by suicide, average survival was 11 months in both the development and validation groups.
Factors associated with higher risk of suicide included: male sex; current or lifetime drug misuse; recent psychiatric disorder; recent use of psychotropic drugs (antidepressants, antipsychotics, mood stabilisers); lifetime and history of self-harm; overnight hospital admission; method of self-harm attributed to psychotropic drug overdose; and attempted hanging, strangulation or suffocation.
The final model contained 11 factors: age, sex, and variables related to substance misuse, mental health and treatment, and history of self-harm. The average age of those in the development and external validation groups was 32, and the proportion of women and girls was 55% and 56%, respectively. Some 44% of the development group and 47% of the validation group had been diagnosed with a mental health issue in the previous 12 months.
Cutting was the principal presenting method of self harm, used by 13% of the development group and 10% of the validation group.
Using a cut-off threshold of 1%, the scoring system correctly identified 68% of those who died by suicide within 6 months, while 71% of those who didn't die were correctly classified as being at low risk. The equivalent figures for risk prediction at 12 months were 82% and 54%, respectively.
If risk categories are applied in this scoring system, 32% of those who died by suicide would have been classified as low risk at 6 months and 18% as low risk at 12 months, assuming a 1% cut-off threshold, note the researchers.
But they emphasise: ‘This is a considerable advance from other models where more than 50% are typically in the low-risk category.’