Most people with type 2 diabetes are overweight, so initial treatment is aimed at reducing weight and increasing physical activity. Even modest weight loss can improve control of blood glucose. If ...drug treatment is necessary, the drug of first choice is metformin. However, some people cannot tolerate metformin, which causes diarrhoea in about 10%, and it cannot be used in people with renal impairment. This review appraises three of the newest class of drugs for monotherapy when metformin cannot be used, the sodium-glucose co-transporter 2 (SGLT2) inhibitors.
To review the clinical effectiveness and cost-effectiveness of dapagliflozin (Farxiga, Bristol-Myers Squibb, Luton, UK), canagliflozin (Invokana, Janssen, High Wycombe, UK) and empagliflozin (Jardiance, Merck & Co., Darmstadt, Germany), in monotherapy in people who cannot take metformin.
MEDLINE (1946 to February 2015) and EMBASE (1974 to February 2015) for randomised controlled trials lasting 24 weeks or more. For adverse events, a wider range of studies was used. Three manufacturers provided submissions.
Systematic review and economic evaluation. A network meta-analysis was carried out involving the three SGLT2 inhibitors and key comparators. Critical appraisal of submissions from three manufacturers.
We included three trials of dapagliflozin and two each for canagliflozin and empagliflozin. The trials were of good quality. The canagliflozin and dapagliflozin trials compared them with placebo, but the two empagliflozin trials included active comparators. All three drugs were shown to be effective in improving glycaemic control, promoting weight loss and lowering blood pressure (BP).
There were no head-to-head trials of the different flozins, and no long-term data on cardiovascular outcomes in this group of patients. Most trials were against placebo. The trials were done in patient groups that were not always comparable, for example in baseline glycated haemoglobin or body mass index. Data on elderly patients were lacking.
Dapagliflozin, canagliflozin and empagliflozin are effective in improving glycaemic control, with added benefits of some reductions in BP and weight. Adverse effects are urinary and genital tract infections in a small proportion of users. In monotherapy, the three drugs do not appear cost-effective compared with gliclazide or pioglitazone, but may be competitive against sitagliptin (Januvia, Boehringer Ingelheim, Bracknell, UK).
The National Institute for Health Research Health Technology Assessment programme.
Objectives The aim of this systematic review is to appraise the evidence for the use of anti-VEGF drugs and steroids in diabetic macular oedema (DMO) as assessed by change in best corrected visual ...acuity (BCVA), central macular thickness and adverse events Data source MEDLINE, EMBASE, Web of Science with Conference Proceedings and the Cochrane Library (inception to July 2012). Certain conference abstracts and drug regulatory web sites were also searched. Study eligibility criteria, participants and interventions Randomised controlled trials were used to assess clinical effectiveness and observational trials were used for safety. Trials which assessed triamcinolone, dexamethasone, fluocinolone, bevacizumab, ranibizumab, pegaptanib or aflibercept in patients with DMO were included. Study appraisal and synthesis methods Risk of bias was assessed using the Cochrane risk of bias tool. Study results are narratively described and, where appropriate, data were pooled using random effects meta-analysis. Results Anti-VEGF drugs are effective compared to both laser and placebo and seem to be more effective than steroids in improving BCVA. They have been shown to be safe in the short term but require frequent injections. Studies assessing steroids (triamcinolone, dexamethasone and fluocinolone) have reported mixed results when compared with laser or placebo. Steroids have been associated with increased incidence of cataracts and intraocular pressure rise but require fewer injections, especially when steroid implants are used. Limitations The quality of included studies varied considerably. Five of 14 meta-analyses had moderate or high statistical heterogeneity. Conclusions and implications of key findings The anti-VEGFs ranibizumab and bevacizumab have consistently shown good clinical effectiveness without major unwanted side effects. Steroid results have been mixed and are usually associated with cataract formation and intraocular pressure increase. Despite the current wider spectrum of treatments for DMO, only a small proportion of patients recover good vision (≥20/40), and thus the search for new therapies needs to continue.
The aim of this systematic review is to look at the barriers to uptake and interventions to improve uptake of postnatal screening in women who have had gestational diabetes mellitus (GDM). Increasing ...postnatal screening rates could lead to timely interventions that could reduce the incidence of type 2 diabetes mellitus (T2DM), the associated long-term health complications, and the financial burden of T2DM. A systematic review of the literature was undertaken. PubMed, Embase, Medline, CINAHL and the Cochrane library databases were searched using well-defined search terms. Predefined inclusion and exclusion criteria were used to identify relevant manuscripts. Data extractions and quality assessments were performed by one reviewer and checked by a second reviewer. Eleven primary studies of various research design and three systematic reviews were included. We identified seven themes within these studies and these were described in two categories, barriers and interventions. There appeared to be no single intervention that would overcome all the identified barriers, however, reminders to women and healthcare professionals appear to be most effective. Uptake rates of testing for T2DM are low in women with GDM. Interventions developed with consideration of the identified barriers to uptake could promote greater numbers of women attending for follow-up.
Insulin is generally administered to people with type 1 diabetes mellitus (T1DM) using multiple daily injections (MDIs), but can also be delivered using infusion pumps. In the UK, pumps are ...recommended for patients with the greatest need and adult use is less than in comparable countries. Previous trials have been small, of short duration and have failed to control for training in insulin adjustment.
To assess the clinical effectiveness and cost-effectiveness of pump therapy compared with MDI for adults with T1DM, with both groups receiving equivalent structured training in flexible insulin therapy.
Pragmatic, multicentre, open-label, parallel-group cluster randomised controlled trial, including economic and psychosocial evaluations. After participants were assigned a group training course, courses were randomly allocated in pairs to either pump or MDI.
Eight secondary care diabetes centres in the UK.
Adults with T1DM for > 12 months, willing to undertake intensive insulin therapy, with no preference for pump or MDI, or a clinical indication for pumps.
Pump or MDI structured training in flexible insulin therapy, followed up for 2 years. MDI participants used insulin analogues. Pump participants used a Medtronic Paradigm
Veo
(Medtronic, Watford, UK) with insulin aspart (NovoRapid, Novo Nordisk, Gatwick, UK).
Primary outcome - change in glycated haemoglobin (HbA
) at 2 years in participants whose baseline HbA
was ≥ 7.5% (58 mmol/mol). Key secondary outcome - proportion of participants with HbA
≤ 7.5% at 2 years. Other outcomes at 6, 12 and 24 months - moderate and severe hypoglycaemia; insulin dose; body weight; proteinuria; diabetic ketoacidosis; quality of life (QoL); fear of hypoglycaemia; treatment satisfaction; emotional well-being; qualitative interviews with participants and staff (2 weeks), and participants (6 months); and ICERs in trial and modelled estimates of cost-effectiveness.
We randomised 46 courses comprising 317 participants: 267 attended a Dose Adjustment For Normal Eating course (132 pump; 135 MDI); 260 were included in the intention-to-treat analysis, of which 235 (119 pump; 116 MDI) had baseline HbA
of ≥ 7.5%. HbA
and severe hypoglycaemia improved in both groups. The drop in HbA
% at 2 years was 0.85 on pump and 0.42 on MDI. The mean difference (MD) in HbA
change at 2 years, at which the baseline HbA
was ≥ 7.5%, was -0.24% 95% confidence interval (CI) -0.53% to 0.05% in favour of the pump (
= 0.098). The per-protocol analysis showed a MD in change of -0.36% (95% CI -0.64% to -0.07%) favouring pumps (
= 0.015). Pumps were not cost-effective in the base case and all of the sensitivity analyses. The pump group had greater improvement in diabetes-specific QoL diet restrictions, daily hassle plus treatment satisfaction, statistically significant at 12 and 24 months and supported by qualitative interviews.
Blinding of pump therapy was not possible, although an objective primary outcome was used.
Adding pump therapy to structured training in flexible insulin therapy did not significantly enhance glycaemic control or psychosocial outcomes in adults with T1DM.
To understand why few patients achieve a HbA
of < 7.5%, particularly as glycaemic control is worse in the UK than in other European countries.
Current Controlled Trials ISRCTN61215213.
This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in
; Vol. 21, No. 20. See the NIHR Journals Library website for further project information.
The National Institute for Health and Care Excellence recommends macular laser to treat diabetic macular oedema with a central retinal subfield thickness of < 400 µm on optical coherence tomography. ...The DIAMONDS (DIAbetic Macular Oedema aNd Diode Subthreshold micropulse laser) trial compared standard threshold macular laser with subthreshold micropulse laser to treat diabetic macular oedema suitable for macular laser.
Determining the clinical effectiveness, safety and cost-effectiveness of subthreshold micropulse laser compared with standard threshold macular laser to treat diabetic macular oedema with a central retinal subfield thickness of < 400 µm.
A pragmatic, multicentre, allocation-concealed, double-masked, randomised, non-inferiority, clinical trial.
Hospital eye services in the UK.
Adults with diabetes and centre-involving diabetic macular oedema with a central retinal subfield thickness of < 400 µm, and a visual acuity of > 24 Early Treatment Diabetic Retinopathy Study letters (Snellen equivalent > 20/320) in one/both eyes.
Participants were randomised 1 : 1 to receive 577 nm subthreshold micropulse laser or standard threshold macular laser (e.g. argon laser, frequency-doubled neodymium-doped yttrium aluminium garnet 532 nm laser); laser treatments could be repeated as needed. Rescue therapy with intravitreal anti-vascular endothelial growth factor therapies or steroids was allowed if a loss of ≥ 10 Early Treatment Diabetic Retinopathy Study letters between visits occurred and/or central retinal subfield thickness increased to > 400 µm.
The primary outcome was the mean change in best-corrected visual acuity in the study eye at 24 months (non-inferiority margin 5 Early Treatment Diabetic Retinopathy Study letters). Secondary outcomes included the mean change from baseline to 24 months in the following: binocular best-corrected visual acuity; central retinal subfield thickness; the mean deviation of the Humphrey 10-2 visual field in the study eye; the percentage of people meeting driving standards; and the EuroQol-5 Dimensions, five-level version, National Eye Institute Visual Function Questionnaire - 25 and Vision and Quality of Life Index scores. Other secondary outcomes were the cost per quality-adjusted life-years gained, adverse effects, number of laser treatments and additional rescue treatments.
The DIAMONDS trial recruited fully (
= 266); 87% of participants in the subthreshold micropulse laser group and 86% of participants in the standard threshold macular laser group had primary outcome data. Groups were balanced regarding baseline characteristics. Mean best-corrected visual acuity change in the study eye from baseline to month 24 was -2.43 letters (standard deviation 8.20 letters) in the subthreshold micropulse laser group and -0.45 letters (standard deviation 6.72 letters) in the standard threshold macular laser group. Subthreshold micropulse laser was deemed to be not only non-inferior but also equivalent to standard threshold macular laser as the 95% confidence interval (-3.9 to -0.04 letters) lay wholly within both the upper and lower margins of the permitted maximum difference (5 Early Treatment Diabetic Retinopathy Study letters). There was no statistically significant difference between groups in any of the secondary outcomes investigated with the exception of the number of laser treatments performed, which was slightly higher in the subthreshold micropulse laser group (mean difference 0.48, 95% confidence interval 0.18 to 0.79;
= 0.002). Base-case analysis indicated no significant difference in the cost per quality-adjusted life-years between groups.
A trial in people with ≥ 400 µm diabetic macular oedema comparing anti-vascular endothelial growth factor therapy alone with anti-vascular endothelial growth factor therapy and macular laser applied at the time when central retinal subfield thickness has decreased to < 400 µm following anti-vascular endothelial growth factor injections would be of value because it could reduce the number of injections and, subsequently, costs and risks and inconvenience to patients.
The majority of participants enrolled had poorly controlled diabetes.
Subthreshold micropulse laser was equivalent to standard threshold macular laser but required a slightly higher number of laser treatments.
This trial is registered as EudraCT 2015-001940-12, ISRCTN17742985 and NCT03690050.
This project was funded by the National Institute for Health and Care Research ( NIHR ) Health Technology Assessment programme and will be published in full in
; Vol. 26, No. 50. See the NIHR Journals Library website for further project information.
Background
Owing to the increasing prevalence of diabetes, the workload related to diabetic macular oedema and proliferative diabetic retinopathy is rising, making it difficult for hospital eye ...services to meet demands.
Objective
The objective was to evaluate the diagnostic performance, cost-effectiveness and acceptability of a new pathway using multimodal imaging interpreted by ophthalmic graders to detect reactivation of diabetic macular oedema/proliferative diabetic retinopathy in previously treated patients.
Design
This was a prospective, case-referent, cross-sectional diagnostic study.
Setting
The setting was ophthalmic clinics in 13 NHS hospitals.
Participants
Adults with type 1 or type 2 diabetes with previously successfully treated diabetic macular oedema/proliferative diabetic retinopathy in one/both eyes in whom, at the time of enrolment, diabetic macular oedema/proliferative diabetic retinopathy could be active or inactive.
Methods
For the ophthalmic grader pathway, review of the spectral domain optical coherence tomography scans to detect diabetic macular oedema, and seven-field Early Treatment Diabetic Retinopathy Study/ultra-wide field fundus images to detect proliferative diabetic retinopathy, by trained ophthalmic graders. For the current standard care pathway (reference standard), ophthalmologists examined patients face to face by slit-lamp biomicroscopy for proliferative diabetic retinopathy and, in addition, spectral domain optical coherence tomography imaging for diabetic macular oedema.
Outcome measures
The primary outcome measure was sensitivity of the ophthalmic grader pathway to detect active diabetic macular oedema/proliferative diabetic retinopathy. The secondary outcomes were specificity, agreement between pathways, cost–consequences, acceptability and the proportion of patients requiring subsequent ophthalmologist assessment, unable to undergo imaging and with inadequate quality images/indeterminate findings. It was assumed for the main analysis that all patients in whom graders diagnosed active disease or were ‘unsure’ or images were ‘ungradable’ required examination by an ophthalmologist.
Results
Eligible participants with active and inactive diabetic macular oedema (152 and 120 participants, respectively) and active and inactive proliferative diabetic retinopathy (111 and 170 participants, respectively) were recruited. Under the main analysis, graders had a sensitivity of 97% (142/147) (95% confidence interval 92% to 99%) and specificity of 31% (35/113) (95% confidence interval 23% to 40%) to detect diabetic macular oedema. For proliferative diabetic retinopathy, graders had a similar sensitivity and specificity using seven-field Early Treatment Diabetic Retinopathy Study sensitivity 85% (87/102), 95% confidence interval 77% to 91%; specificity 48% (77/160), 95% confidence interval 41% to 56% or ultra-wide field imaging sensitivity 83% (87/105), 95% confidence interval 75% to 89%; specificity 54% (86/160), 95% confidence interval 46% to 61%. Participants attending focus groups expressed preference for face-to-face evaluations by ophthalmologists. In the ophthalmologists’ absence, patients voiced the need for immediate feedback following grader’s assessments, maintaining periodic evaluations by ophthalmologists. Graders and ophthalmologists were supportive of the new pathway. When compared with the reference standard (current standard pathway), the new grader pathway could save £1390 per 100 patients in the review of people with diabetic macular oedema and, depending on the imaging modality used, between £461 and £1189 per 100 patients in the review of people with proliferative diabetic retinopathy.
Conclusions
For people with diabetic macular oedema, the ophthalmic grader pathway appears safe and cost saving. The sensitivity of the new pathway to detect active proliferative diabetic retinopathy was lower, but may still be considered acceptable for patients with proliferative diabetic retinopathy previously treated with laser. Suggestions from focus group discussions should be taken into consideration if the new pathway is introduced to ensure its acceptability to users.
Limitations
Lack of fundus fluorescein angiography to confirm diagnosis of active proliferative diabetic retinopathy.
Future work
Could refinement of the new pathway increase its sensitivity to detect proliferative diabetic retinopathy? Could artificial intelligence be used for automated reading of images in this previously treated population?
Trial registration
Current Controlled Trials ISRCTN10856638 and ClinicalTrials.gov NCT03490318.
Funding
This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in
Health Technology Assessment
Vol. 25, No. 32. See the NIHR Journals Library website for further project information.
Type 2 diabetes is treated in a stepwise manner, progressing from diet and physical activity to oral antidiabetic agents and insulin. The oral agent pioglitazone is licensed for use with insulin when ...metformin is contraindicated or not tolerated. This systematic review and meta-analysis investigates the extent to which adding pioglitazone to insulin-containing regimens produces benefits in terms of patient-relevant outcomes.
Medline, Embase, and the Cochrane Library were searched for randomised controlled trials comparing pioglitazone in combination with any insulin-containing regimen in comparison with the same insulin regimen alone in patients with type 2 diabetes. Outcomes investigated included HbA1c, hypoglycaemia, weight, and adverse events. Studies were selected, assessed and summarised according to standard systematic review methodology and in a meta-analysis. We included eight trials that examined the benefits of adding pioglitazone to an insulin regimen and studied a total of 3092 patients with type 2 diabetes. All studies included patients with previously inadequate glucose control. Trial duration was between 12 weeks and 34.5 months. The trials used pioglitazone doses of up to 45 mg/day. In our meta-analysis, the mean reduction in HbA1c was 0.58% (95% CI: -0.70, -0.46, p<0.00001). Hypoglycaemic episodes were slightly more frequent in the pioglitazone arms (relative risk 1.27; 95% CI: 0.99, 1.63, p = 0.06). Where reported, HDL-cholesterol tended to be increased with pioglitazone. Patients on pioglitazone tended to gain more weight than those who were not, with an average difference of almost 3 kg. Peripheral oedema was more frequent in the pioglitazone groups. None of the studies reported on fractures in women, and data on cardiovascular events were inconclusive, with most studies being too short or too small to assess these long-term outcomes.
When added to insulin regimens, pioglitazone confers a small advantage in terms of HbA1c in type 2 diabetes patients with previous inadequate glucose control, but at the cost of increased hypoglycaemia and weight gain. Other considerations include the risk of heart failure, fractures in women, a reduced insulin dose, and the net financial cost.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Aim - to survey members of Diabetes UK who had Type 2 diabetes and who used self monitoring of blood glucose (SMBG), to elicit their views on its usefulness in the management of their diabetes, and ...how they used the results. A questionnaire was developed for the Diabetes UK website. The questionnaire was posted on the Diabetes UK website until over 500 people had responded. Questions asked users to specify the benefits gained from SMBG, and how these benefits were achieved. We carried out both quantitative analysis and a thematic analysis for the open ended free-text questions.
554 participants completed the survey, of whom 289 (52.2%) were male. 20% of respondents were recently diagnosed (< 6 months). Frequency of SMBG varied, with 43% of participants testing between once and four times a day and 22% testing less than once a month or for occasional periods.80% of respondents reported high satisfaction with SMBG, and reported feeling more 'in control' of their diabetes management using it. The most frequently reported use of SMBG was to make adjustments to food intake or confirm a hyperglycaemic episode.Women were significantly more likely to report feelings of guilt or self-chastisement associated with out of range readings (p = < .001).
SMBG was clearly of benefit to this group of confirmed users, who used the results to adjust diet, physical activity or medications. However many individuals (particularly women) reported feelings of anxiety and depression associated with its use.
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