Sitagliptin is effective and safe as add-on to insulin in patients with absolute insulin deficiency: a case series

<p>Abstract</p> <p>Introduction</p> <p>It is generally believed that incretin-based therapies are effective in patients possessing certain levels of preserved β-cell function. So far, there are no reports that show the effectiveness of dipeptidyl peptidase-4 inhibitors in patients who absolutely lack the capacity for endogenous insulin secretion.</p> <p>Case presentation</p> <p>This report describes the efficacy of sitagliptin in three Japanese patients (a 91-year-old Japanese woman with type 1 diabetes, a 54-year-old Japanese man with type 2 diabetes and a 30-year-old Japanese man with features of both type 1 and type 2 diabetes) who had no detectable post-meal C-peptide levels. Although they were receiving intensive insulin therapy together with some oral hypoglycemic agents, their glycemic control remained poor. Sitagliptin was added to the ongoing therapeutic regimen to provide better glycemic control. Although these patients had mild hypoglycemia, effective reductions of hemoglobin A1c levels were observed without any adverse events in the liver and kidney during the following 24 weeks. Two of the patients were able to reduce their insulin doses, and one of the patients could discontinue one of the oral hypoglycemic agents. There was no weight gain or gastrointestinal complaints among the three patients. Post-meal C-peptide levels remained undetectable after sitagliptin treatment.</p> <p>Conclusion</p> <p>This report demonstrates that sitagliptin is effective and safe as an add-on therapy to insulin in reducing blood glucose levels in patients who absolutely lack the capacity for endogenous insulin secretion. The improvement seen in glycemic control could not be due to enhanced endogenous insulin secretion, since post-meal C-peptide levels remained undetectable after sitagliptin treatment, but it could be a result of other factors (for example, suppression of glucagon levels). However, the glucagon-suppressive effect of sitagliptin is known to be rather weak and short-lived. Given this background, a novel hypothesis that the glycemic effects of this drug may be caused by mechanisms that are independent of the glucagon-like peptide 1 axis (extra-pancreatic effect) will be discussed.</p

Clinical effectiveness and cost-effectiveness of pegvisomant for the treatment of acromegaly: a systematic review and economic evaluation

Background: Acromegaly, an orphan disease usually caused by a benign pituitary tumour, is characterised by hyper-secretion of growth hormone (GH) and insulin-like growth factor I (IGF-1). It is associated with reduced life expectancy, cardiovascular problems, a variety of insidiously progressing detrimental symptoms and metabolic malfunction. Treatments include surgery, radiotherapy and pharmacotherapy. Pegvisomant (PEG) is a genetically engineered GH analogue licensed as a third or fourth line option when other treatments have failed to normalise IGF-1 levels. Methods: Evidence about effectiveness and cost-effectiveness of PEG was systematically reviewed. Data were extracted from published studies and used for a narrative synthesis of evidence. A decision analytical economic model was identified and modified to assess the cost-effectiveness of PEG. Results: One RCT and 17 non-randomised studies were reviewed for effectiveness. PEG substantially reduced and rapidly normalised IGF-1 levels in the majority of patients, approximately doubled GH levels, and improved some of the signs and symptoms of the disease. Tumour size was unaffected at least in the short term. PEG had a generally safe adverse event profile but a few patients were withdrawn from treatment because of raised liver enzymes. An economic model was identified and adapted to estimate the lower limit for the cost-effectiveness of PEG treatment versus standard care. Over a 20 year time horizon the incremental cost-effectiveness ratio was pound81,000/QALY and pound212,000/LYG. To reduce this to pound30K/QALY would require a reduction in drug cost by about one third. Conclusion: PEG is highly effective for improving patients' IGF-1 level. Signs and symptoms of disease improve but evidence is lacking about long term effects on improved signs and symptoms of disease, quality of life, patient compliance and safety. Economic evaluation indicated that if current standards (UK) for determining cost-effectiveness of therapies were to be applied to PEG it would be considered not to represent good value for money

Reducing length of stay for acute diabetic foot episodes: employing an extended scope of practice podiatric high-risk foot coordinator in an acute foundation trust hospital

BACKGROUND: To enhance the acute management of people with diabetic foot disease requiring admission, an extended scope of practice, podiatric high-risk foot coordinator position, was established at the Great Western Hospital, Swindon in 2010. The focus of this new role was to facilitate more efficient and timely management of people with complex diabetic foot disease. The aim of this project was to investigate the impact of the podiatric high-risk foot coordinator role on length of stay, rate of re-admission and bed cost. METHOD: This study evaluated the difference in length of stay and rate of re-admission between an 11- month pre-pilot period (November 2008 to October 2009) and a 10-month pilot period (August 2010 to June 2011). The estimated difference in bed cost between the pre-pilot and pilot audits was also calculated. Inclusion criteria were restricted to inpatients admitted with a diabetic foot ulcer, gangrene, cellulitis or infection as the primary cause for admission. Eligible records were retrieved using ICD-10 (V9) coding via the hospital clinical audit department for the pre-pilot period and a unique database was used to source records for the pilot phase. RESULTS: Following the introduction of the podiatric high-risk foot coordinator, the average length of stay reduced from 33.7 days to 23.3 days (mean difference 10.4 days, 95% CI 0.0 to 20.8, p = 0.050). There was no statistically significant difference in re-admission rate between the two study periods, 17.2% (95% CI 12.2% to 23.9%) in the pre-pilot phase and 15.4% (95% CI 12.0% to 19.5%) in the pilot phase (p = 0.820). The extrapolated annual cost saving following the implementation of the new coordinator role was calculated to be £234,000 for the 2010/2011 year. CONCLUSIONS: This audit found that the extended scope of practice coordinator role may have a positive impact on reducing length of stay for diabetic foot admissions. This paper advocates the role of a podiatric high-risk foot coordinator utilising an extended scope of practice model, although further research is needed

The endocrine tumor summit 2008: appraising therapeutic approaches for acromegaly and carcinoid syndrome

The Endocrine Tumor Summit convened in December 2008 to address 6 statements prepared by panel members that reflect important questions in the treatment of acromegaly and carcinoid syndrome. Data pertinent to each of the statements were identified through review of pertinent literature by one of the 9-member panel, enabling a critical evaluation of the statements and the evidence supporting or refuting them. Three statements addressed the validity of serum growth hormone (GH) and insulin-like growth factor-I (IGF-I) concentrations as indicators or predictors of disease in acromegaly. Statements regarding the effects of preoperative somatostatin analog use on pituitary surgical outcomes, their effects on hormone and symptom control in carcinoid syndrome, and the efficacy of extended dosing intervals were reviewed. Panel opinions, based on the level of available scientific evidence, were polled. Finally, their views were compared with those of surveyed community-based endocrinologists and neurosurgeons