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

New plan announced by NHS Chief to tackle Type 2 diabetes epidemic

NHS England | November 2018 |Very low calorie diets part of NHS action to tackle growing obesity and Type 2 diabetes epidemic

NHS Chief executive Simon Stevens has announced that people recently diagnosed with Type 2 diabetes will be trialled as part of a new NHS long term plan, which will increase the focus on prevention as well as treatment.

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As well as improving the health of patients,this will also save the NHS money that can be reinvested in frontline care. Currently, the health service in England spends around 10% of its budget on treating diabetes.

The scaling up of the NHS DPP scheme, the first in the world to become available country-wide, comes after it proved even more successful than planned with patients losing on average a kilogram more than expected.

The nine month programme helps people to:

  • achieve a healthy weight
  • improve overall nutrition
  • increase levels of physical activity

Online versions of the DPP, which involve wearable technologies and apps to help those at risk of Type 2 Diabetes, will also be provided for patients who find it difficult to attend sessions because of work or family commitments (Source: NHS England).

Full news release available from NHS England 

 

In the news:

BBC News Type 2 diabetes: NHS to offer 800-calorie diet treatment

ITV News Liquid diet to be prescribed to diabetes patients

Evening Standard Liquid diet for type 2 diabetes patients after trial puts condition into remission

Self-monitoring of blood glucose provides no important benefit for most people with type 2 diabetes

NIHR | October 2018 | Self-monitoring of blood glucose provides no important benefit for most people with type 2 diabetes

Patients with type 2 diabetes who monitor their blood glucose themselves may see small, short-term improvements in blood sugar control. This is not enough to be clinically important or outweigh the costs and personal inconvenience of long-term self-testing, reports an NIHR Signal. 

The signal highlights a systematic review (SR) that identified 24 recent randomised controlled trials involving more than  5000 people with type 2 diabetes to compare self- monitoring with control strategies where people were not taking insulin.

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Self-monitoring gave a 0.3 percentage point reduction in glycated haemoglobin (HbA1c) at six months. This is just below the 0.4% threshold for a meaningful clinical difference in this measure of average 3-month sugar control. People who had poorer blood glucose control at the start saw a greater benefit. However, there was no difference between the self-monitoring and control groups by 12 months.

The review supports current guideline recommendations that self-monitoring is not routinely used for people with type 2 diabetes controlled on diet or tablets (Source: NIHR).

Read the signal in full from NIHR 

Machry, R. V., Rados, D. V., de Gregório, G. R., & Rodrigues, T. C. |2018|  Self-Monitoring Blood Glucose improves glycemic control in Type 2 Diabetes without intensive treatment: a systematic review and meta-analysis|  Diabetes research and clinical practice| 

Abstract

AIMS: Systematic review and meta-analysis to evaluate the effect of Self-Monitoring of Blood Glucose (SMBG) on glycemic control in patients with type 2 Diabetes (T2D).

METHODS: We searched the Medline, Embase, Cochrane Central, and ClinicalTrials.gov databases up to 20 July 2017. We also performed a manual search of abstracts from recent meetings of the American Diabetes Association and the European Association for the Study of Diabetes.

STUDY SELECTION: randomized controlled trials (RCTs) conducted in patients with T2D comparing any kind of SMBG to a control group. Two independent reviewers assessed the eligibility of references. Influence of SMBG in glycated hemoglobin (HbA1c) was aggregated as weighted mean difference accessed by direct random effect meta-analyses at 12, 24 weeks and 1 year. Sub-analyses were made to assess the effects of previous glycemic control and number of tests performed.

RESULTS: SMBG was associated with a reduction of HbA1c at 12 weeks and 24 weeks, but no difference was found for 1 year. Subgroup analysis including studies with baseline HbA1c greater than 8% showed a higher reduction of HbA1c: -0.83% at 12 weeks, and -0.48%  at 24 weeks, with no difference for 1 year nor for the stratification for number the tests.

CONCLUSION: SMBG seems to lead to a slightly better glycemic control in the short term in patients with T2D. Patients decompensated at baseline appear to have the greatest benefit. PROSPERO register: CRD42016033558.

 

Insulin pumps offer little value over multiple injections for children at the onset of diabetes

NIHR | November 2018 | Insulin pumps offer little value over multiple injections for children at the onset of diabetes 

Young people newly diagnosed with type 1 diabetes achieve similar blood glucose control by 12 months if they are treated with multiple daily insulin injections or continuously via an insulin pump, according to the findings of a randomised controlled trial (RCT) that looked at 93 children  up to 15 years of age  in 15 centres in England all  newly diagnosed with type 1 diabetes. The control group  received multiple daily injections (4 or more injections daily including both short- and long-acting insulin) and the intervention group received continuous subcutaneous infusion of short-acting insulin via a pump.

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The RCT found that parent-reported quality of life was higher in the artificial pancreas group than the in the group with daily injections.  Currently, both regimens are used in the management of type 1 diabetes, with the number of children using insulin pumps is increasing. This NIHR-funded trial indicates that at an additional cost of £1,863 per patient annually with equivalent outcomes, the high costs of insulin pumps seem unjustified at this stage of the condition (Source: NIHR Signal).

Full reference: Blair,  J. | 2018 | Continuous subcutaneous insulin infusion versus multiple daily injections in children and young people at diagnosis of type 1 diabetes: the SCIPI RCT| Published on 15 August 2018 | Health Technology Assessment | Vol. 22| Issue 42 | 10.3310/signal-000680

Abstract

Background The risk of developing long-term complications of type 1 diabetes (T1D) is related to glycaemic control and is reduced by the use of intensive insulin treatment regimens: multiple daily injections (MDI) (more than or equal to 4) and continuous subcutaneous insulin infusion (CSII). Despite a lack of evidence that the more expensive treatment with CSII is superior to MDI, both treatments are used widely within the NHS.
Objectives (1) To compare glycaemic control during treatment with CSII and MDI and (2) to determine safety and cost-effectiveness of the treatment, and quality of life (QoL) of the patients.
Design A pragmatic, open-label randomised controlled trial with an internal pilot and 12-month follow-up with 1 : 1 web-based block randomisation stratified by age and centre.
Setting Fifteen diabetes clinics in hospitals in England and Wales.
Participants Patients aged 7 months to 15 years. Interventions Continuous subsutaneous insulin infusion or MDI initiated within 14 days of diagnosis of T1D.
Data sources Data were collected at baseline and at 3, 6, 9 and 12 months using paper forms and were entered centrally. Data from glucometers and CSII were downloaded. The Health Utilities Index Mark 2 was completed at each visit and the Pediatric Quality of Life Inventory (PedsQL, diabetes module) was completed at 6 and 12 months. Costs were estimated from hospital patient administration system data.
Outcomes The primary outcome was glycosylated haemoglobin (HbA1c) concentration at 12 months. The secondary outcomes were (1) HbA1c concentrations of less than  48 mmol/mol, (2) severe hypoglycaemia, (3) diabetic ketoacidosis (DKA), (4) T1D- or treatment-related adverse events (AEs), (5) change in body mass index and height standard deviation score, (6) insulin requirements, (7) QoL and (8) partial remission rate. The economic outcome was the incremental cost per quality-adjusted life-year (QALY) gained.
Results A total of 293 participants, with a median age of 9.8 years (minimum 0.7 years, maximum 16 years), were randomised  between May 2011 and January 2015. Primary outcome data were available for 97% of participants. At 12 months, age-adjusted least mean squares HbA1c concentrations were comparable between groups: CSII, 60.9 mmol/mol; MDI, 58.5 mmol/mol; and the difference of CSII – MDI, 2.4 mmol/mol. For HbA1c concentrations of less than 48 mmol/mol (CSII, 22/143 participants; MDI, 29/142 participants), the relative risk was 0.75 (95% CI 0.46 to 1.25), and for partial remission rates (the relative risk was 0.74 . The incidences of severe hypoglycaemia (CSII, 6/144; MDI, 2/149 participants) and DKA ( were low. In total, 68 AEs (14 serious) were reported during CSII treatment and 25 AEs (eight serious) were reported during MDI treatment. Growth outcomes did not differ. The reported insulin use was higher with CSII . QoL was slightly higher for those randomised to CSII. From a NHS perspective, CSII was more expensive than MDI mean total cost (£1863, 95% CI £1620 to £2137) with no additional QALY gains.
Limitations
Generalisability beyond 12 months is uncertain.
Conclusions No clinical benefit of CSII over MDI was identified. CSII is not a cost-effective treatment in patients representative of the study population. Future work Longer-term follow-up is required to determine if clinical outcomes diverge after 1 year. A qualitative exploration of patient and professional experiences of MDI and CSII should be considered.

 

Type 2 diabetes affects 7000 young people in England and Wales, analysis shows

Iacobucci,  G. | 2018 | Type 2 diabetes affects 7000 young people in England and Wales, analysis shows

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Currently, over a third of children in England (34%) are overweight or obese by the time they leave primary school. Diabetes UK warned that thousands more children could have type 2 diabetes diagnosed without decisive support for young people (Source: BMJ)

Read the full BMJ article via Open Athens 

In the news:

BBC News Type 2 diabetes affects 7,000 under-25s in England and Wales 

The Guardian Type 2 diabetes now affects nearly 7,000 young Britons 

National Diabetes Audit Report 1- Findings and Recommendations 2016-17

NHS Digital | November 2018 | National Diabetes Audit Report 1- Findings and Recommendations 2016-17

This report details the findings for the 2016-17 audit. The audit collected data during the Summer of 2017, for the period 1 January 2016 to 31 March 2017 and contains the full key findings, recommendations, results of analysis for multiple readings, and information for learning disability and severe mental illness.

See NHS Digital for details 

Closed loop insulin pump improves glucose control in hospital for people with type 2

NIHR | November 2018 | ‘Artificial pancreas’ improves glucose control in hospital patients with type 2 diabetes

A closed loop insulin pump, also referred to as an ‘artificial pancreas’   which continuously monitor blood glucose and administer insulin accordingly, can improve blood glucose control among patients with type 2 diabetes admitted to hospital for non-critical care. Those using the system spent about six hours longer in the target range, and this could hasten their recovery and reduce staff workload.

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The randomised controlled trial (RCT) involved  over 100 adults with type 2 diabetes admitted to general wards at two hospitals in the UK and Switzerland, all with raised blood sugar who needed insulin. Two-thirds of patients were already having insulin as part of their usual treatment.  Patients either continued with their usual insulin and glucose lowering treatments, which clinicians adjusted according to  conventional glucose measurements or they were assigned to the intervention and used the closed loop system to deliver insulin.  All patients wore an implanted continuous glucose monitor to record their glucose levels and were followed up after two weeks or until hospital discharge.  The study found that closed loop insulin delivery increased the percentage of time that blood glucose was in the target range of 100-180 mg per decilitre  by about 6 hours per day: 65.8% of the time in range (±16.8%) compared with 41.5% (±16.9%) in the control group, 

Read the signal in full at NIHR 

“The burden of diabetes is increasing, as is the proportion of hospital in-patients with diabetes. This study evaluates an alternative technology an automated closed-loop (also known as Artificial Pancreas) for improving the glucose control among hospital in-patients with diabetes.

The target glucose range was 5.6 to 10.0 mmol/L, with the standard care patients spending 12 hours/day hyperglycaemic (mean glucose 10.4 mmol/L). The closed-loop group spent about six hours more within range and six hours less with glucose levels 10.0 mmol/L or more.

The study highlights the inadequacy of current in-patient diabetes care and suggests that new technologies may allow for in-patient care that is safer and more effective than current clinical approaches.”

Dr HR Murphy, Professor of Medicine (Diabetes and Antenatal Care), Norwich Medical School

Source: NIHR

Abstract 

Background In patients with diabetes, hospitalization can complicate the achievement of recommended glycemic targets. There is increasing evidence that a closed-loop delivery system (artificial pancreas) can improve glucose control in patients with type 1 diabetes. We wanted to investigate whether a closed-loop system could also improve glycemic control in patients with type 2 diabetes who were receiving noncritical care.

Methods In this randomized, open-label trial conducted on general wards in two tertiary hospitals located in the United Kingdom and Switzerland, we assigned 136 adults with type 2 diabetes who required subcutaneous insulin therapy to receive either closed-loop insulin delivery (70 patients) or conventional subcutaneous insulin therapy, according to local clinical practice (66 patients). The primary end point was the percentage of time that the sensor glucose measurement was within the target range of 100 to 180 mg per deciliter (5.6 to 10.0 mmol per liter) for up to 15 days or until hospital discharge.

Results The mean (+/-SD) percentage of time that the sensor glucose measurement was in the target range was 65.8+/-16.8% in the closed-loop group and 41.5+/-16.9% in the control group, a difference of 24.3+/-2.9 percentage points; values above the target range were found in 23.6+/-16.6% and 49.5+/-22.8% of the patients, respectively, a difference of 25.9+/-3.4 percentage points. The mean glucose level was 154 mg per deciliter (8.5 mmol per liter) in the closed-loop group and 188 mg per deciliter (10.4 mmol per liter) in the control group (P less than0.001). There was no significant between-group difference in the duration of hypoglycemia or in the amount of insulin that was delivered (median dose, 44.4 U and 40.2 U, respectively; P=0.50). No episode of severe hypoglycemia or clinically significant hyperglycemia with ketonemia occurred in either trial group.

Conclusions Among inpatients with type 2 diabetes receiving noncritical care, the use of an automated, closed-loop insulin-delivery system resulted in significantly better glycemic control than conventional subcutaneous insulin therapy, without a higher risk of hypoglycemia. (Funded by Diabetes UK and others; ClinicalTrials.gov number, NCT01774565 .).

 

 

 

 

 

Full reference: Bally L, Thabit H, Hartnell S et al. | 2018 |  Closed-loop insulin delivery for glycemic control in noncritical care|  New England Journal of  Medicine | 379| 6| P. 547-56.

Diabetes UK survey reveals carers experience mental health problems

Diabetes Times | November 2018 | Diabetes UK survey reveals carers experience mental health problems

An online survey from Diabetes UK demonstrated that more than three quarters (77 per cent) of respondents said that they sometimes or often feel down because of their family member’s diabetes.

In the survey one third of carers (n=228) wanted their family member to see a diabetes specialist nurse (DSN) more frequently, while  just over one-tenth (11 per cent) wanted a trained counsellor or psychologist to support the children or adults with diabetes they care for.

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Other findings include:

  • More than a quarter (n= 178) say that if they could change one thing about the healthcare they experience, it would be to receive more information and support to manage the condition day to day.
  • Carers of children and young people  with type 1 diabetes say it is challenging when people do not understand the realities of their child’s condition, and that emotional support would reduce the strain on them to ‘appear strong’ at all times.
  • Carers of older people with type 2 diabetes cited having the opportunity to be themselves, not just a carer, as being important for their well-being, they also would like to receive support from more experienced peers. (Source: Diabetes Times)

 

See also:

NHS to provide life changing glucose monitors for Type 1 diabetes patients

NHS England | November 2018 | NHS to provide life changing glucose monitors for Type 1 diabetes patients

Simon Stevens Chief Executive of NHS England  has announced that thousands of people with diabetes will be able to access Freestyle Libre; a wearable sensor that means those with the condition no longer need to rely on inconvenient and sometimes painful finger prick blood tests, as the device works by relaying glucose levels to a smart phone or e-reader.  This announcement marks an end to the current variation  some people in different parts of the country were experiencing. 

 

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The pioneering technology should ultimately help people with Type 1 diabetes achieve better health outcomes and benefits for patients include:

  • Easily noticing when sugar levels are starting to rise or drop, so action can be taken earlier
  • Giving patients more confidence in managing their own condition
  • Not having to do as many finger-prick checks (Source: NHS England)

Read the full announcement from NHS England

In the media:

BBC News Diabetes glucose monitors ‘available to thousands more’

 

World Diabetes Day: 14 November 2018

World Diabetes Day | November 2018 | World Diabetes Day: 14 November 2018

Today (14 November 2018) is World Diabetes Day, which is part of a global campaign led by the International Diabetes Federation to raise awareness of the condition.

This year’s theme is The Family and Diabetes, the campaign has a two-year timeline to best facilitate planning, development, promotion and participation. 

Its foci are to :

  • Raise awareness of the impact that diabetes has on the family and support network of those affected.
  • Promote the role of the family in the management, care, prevention and education of diabetes (Source: World Diabetes Day).

Further information from World Diabetes Day